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Surgery_Schwartz. are best managed conserva-tively. The preferred treatment for symptomatic cysts is ultra-soundor CT-guided percutaneous cyst aspiration followed by sclerotherapy. This approach is approximately 90% effective in controlling symptoms and ablating the cyst cavity. If percu-taneous treatment is unavailable or ineffective, treatment may include either laparoscopic or open surgical cyst fenestration. The laparoscopic approach is being used more frequently and is 90% effective. The excised cyst wall is sent for pathologic analysis to exclude the presence of carcinoma, and the remain-ing cyst wall must be carefully inspected for evidence of neo-plastic change. If such change is present, complete resection is required, either by enucleation or formal hepatic resection.Biliary CystadenomaBiliary cystadenomas are slow-growing, unusual, benign lesions that most commonly present as large lesions in the right lobe of the liver. Although these lesions are usually benign, they can undergo malignant


Surgery_Schwartz

Surgery_Schwartz. are slow-growing, unusual, benign lesions that most commonly present as large lesions in the right lobe of the liver. Although these lesions are usually benign, they can undergo malignant transformation. Patients with biliary cystad-enomas commonly present with abdominal pain. An abdominal mass occasionally can be identified on physical examination. In contrast to simple cysts, biliary cystadenomas have walls that appear thicker with soft tissue nodules and septations that usu-ally enhance. The protein content of the fluid can be variable and can affect the radiographic images on CT and MRI. Surgical resection is the preferred mode of treatment.Polycystic Liver DiseaseAdult polycystic liver disease (PCLD) occurs as an autosomal dominant disease and usually presents in the third decade of life. Approximately 44% to 76% of affected families are found to have mutations of PKD1, and approximately 75% have muta-tions of PKD2.72 The prevalence and number of hepatic cysts


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Surgery_Schwartz. third decade of life. Approximately 44% to 76% of affected families are found to have mutations of PKD1, and approximately 75% have muta-tions of PKD2.72 The prevalence and number of hepatic cysts Brunicardi_Ch31_p1345-p1392.indd 137320/02/19 2:36 PM 1374SPECIFIC CONSIDERATIONSPART IIare higher in females and increase with advancing age and with increasing severity of renal cystic disease and renal dysfunc-tion. Patients with a small number of cysts or with small cysts (<2 cm) usually remain asymptomatic. In contrast, patients who develop many or large cysts, with a cyst-to-parenchymal vol-ume ratio of >1, usually develop clinical symptoms, including abdominal pain, distension, shortness of breath, and early satiety. Disease progression often results in renal failure and the need for hemodialysis. In most patients, the liver parenchymal vol-ume and synthetic function are preserved despite extensive cystic disease. Hepatic decompensation, variceal hemorrhage, ascites, and


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Surgery_Schwartz. for hemodialysis. In most patients, the liver parenchymal vol-ume and synthetic function are preserved despite extensive cystic disease. Hepatic decompensation, variceal hemorrhage, ascites, and encephalopathy develop rarely in patients with PCLD and only in those with massive cystic disease. The most common liver-specific complications associated with PCLD are intracystic hemorrhage, infection, and posttraumatic rup-ture. The most common abnormal biochemical test finding is a modestly elevated γ-glutamyltransferase level, and the most useful imaging tests are CT or MRI of the abdomen, which will demonstrate the characteristic polycystic appearance. Other conditions that may be associated with PCLD include cerebral aneurysm, diverticulosis, mitral valve prolapse, and inguinal hernia.The principal aim of treatment for PCLD is to ameliorate symptoms by decreasing liver volume. Medical therapy options for PCLD remain experimental at this time. Somatostatin ana-logs such as octreotide


Surgery_Schwartz

Surgery_Schwartz. principal aim of treatment for PCLD is to ameliorate symptoms by decreasing liver volume. Medical therapy options for PCLD remain experimental at this time. Somatostatin ana-logs such as octreotide and lanreotide have been shown to modestly reduce liver volume and are generally well tolerated. Sirolimus and other mammalian target of rapamycin (mTOR) inhibitors possess antiproliferative effects and thus have been postulated to slow disease progression. The effectiveness of these medical measures in relieving symptoms among patients with PCLD, however, remains to be proven.73Cyst aspiration and sclerotherapy entail puncture of a cyst with an aspiration needle followed by injection of a scleros-ing agent that causes destruction of the epithelial lining thereby inhibiting fluid production. Common agents used for sclerosis include ethanol, minocycline, and tetracycline. This technique may be considered if the patient has one or a few dominant cysts, each measuring over 5 cm. Appropriate


Surgery_Schwartz

Surgery_Schwartz. Common agents used for sclerosis include ethanol, minocycline, and tetracycline. This technique may be considered if the patient has one or a few dominant cysts, each measuring over 5 cm. Appropriate candidates for sclerotherapy can experience a complete resolution of symp-toms, but patients with numerous cysts often do not improve when this technique is used. This procedure is generally well tolerated, with the most common complication being pain from the instillation of ethanol.Cyst fenestration, or surgical unroofing of the cyst, can be performed via an open or laparoscopic approach in symptomatic patients.74 This approach allows multiple cysts to be treated dur-ing a single procedure, but carries the risk of potential surgical complications, including ascites, pleural effusion, hemorrhage, and biliary leakage. Immediate symptom relief can be achieved in up to 92% of cases, but 22% of patients eventually develop recurrence of their symptoms.Hepatic resection can be considered for


Surgery_Schwartz

Surgery_Schwartz. and biliary leakage. Immediate symptom relief can be achieved in up to 92% of cases, but 22% of patients eventually develop recurrence of their symptoms.Hepatic resection can be considered for PCLD patients with massive hepatomegaly, when fenestration alone is unlikely to significantly reduce liver volume. Appropriate candidates are those with portions of liver that harbor numerous cysts, but have at least one spared segment with predominantly normal liver parenchyma. Because the intrahepatic vascular and biliary anat-omy can be distorted by the cysts, PCLD patients undergoing hepatic resection are at increased risk for hemorrhagic and bili-ary complications. Furthermore, adhesion formation after liver resection can increase the technical complexity of future OLT. Significant symptom relief has been reported in up to 86% of PCLD patients following hepatic resection.OLT represents the only definitive therapy for patients with symptomatic PCLD. This therapeutic option is indicated in


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Surgery_Schwartz. has been reported in up to 86% of PCLD patients following hepatic resection.OLT represents the only definitive therapy for patients with symptomatic PCLD. This therapeutic option is indicated in patients with severely disabling symptoms that lead to a poor quality of life or in those who have developed untreatable com-plications such as portal hypertension and nutritional depriva-tion. If the patient has severe renal insufficiency from polycystic kidney disease, consideration should be given to combined liver-kidney transplantation. Because of the genetic basis of PCLD, living-donor transplantation should be considered only if the presence of PCLD in the donor can be ruled out.Caroli’s DiseaseCaroli’s disease is a syndrome of congenital ductal plate mal-formations of the intrahepatic bile ducts and is characterized by segmental cystic dilatation of the intrahepatic biliary radicals.74 Caroli’s disease also is associated with an increased incidence of biliary lithiasis, cholangitis,


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Surgery_Schwartz. ducts and is characterized by segmental cystic dilatation of the intrahepatic biliary radicals.74 Caroli’s disease also is associated with an increased incidence of biliary lithiasis, cholangitis, and biliary abscess formation. Caroli’s disease usually occurs in the absence of cirrhosis and is associated with cystic renal disease.75 The most common presenting symptoms include fever, chills, and abdominal pain. Most patients present by the age of 30 years, and males and females are affected equally. Rarely, patients can present later in life with complications secondary to portal hyperten-sion. Approximately 33% of affected patients develop biliary lithiasis, and 7% develop cholangiocarcinoma. The diagnosis of Caroli’s disease is made based on imaging studies. Magnetic resonance cholangiopancreatography, ERCP, and percutaneous transhepatic cholangiography provide more detailed imaging of the biliary tree and confirm communication of the intrahepatic cysts with the biliary tree, which


Surgery_Schwartz

Surgery_Schwartz. ERCP, and percutaneous transhepatic cholangiography provide more detailed imaging of the biliary tree and confirm communication of the intrahepatic cysts with the biliary tree, which is necessary to solidify the diagnosis. Treatment consists of biliary drainage, with ERCP and percutaneous transhepatic cholangiography serving as first-line therapeutic modalities. If the disease is limited to a single lobe of the liver, hepatic resection can be beneficial. Liver resec-tion can be considered in the patient with hepatic decompensa-tion or unresponsive recurrent cholangitis and possibly in the patient with a small (T1 or T2) cholangiocarcinoma.BENIGN LIVER LESIONSThe liver is an organ that is commonly involved either primarily or secondarily with vascular, metabolic, infectious, and malig-nant processes. Many classification schemes are used to help narrow the differential diagnosis of liver lesions: solid or cystic, single or multiple, cell of origin (hepatocellular, cholangiocel-lular, or


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Surgery_Schwartz. processes. Many classification schemes are used to help narrow the differential diagnosis of liver lesions: solid or cystic, single or multiple, cell of origin (hepatocellular, cholangiocel-lular, or mesenchymal), and benign or malignant. Benign liver lesions occur in up to 20% of the general population and are much more common than malignant tumors. The most common benign lesions are cysts, hemangiomas, focal nodular hyperplasia (FNH), and hepatocellular adenomas (see Table 31-6). Many of these lesions have typical features in imaging studies that help confirm the diagnosis.CystHepatic cysts are the most frequently encountered liver lesion overall and are described in detail in the section “Hepatic Cysts.” Cystic lesions of the liver can arise primarily (congeni-tal) or secondarily from trauma (seroma or biloma), infection (pyogenic or parasitic), or neoplastic disease. Congenital cysts are usually simple cysts containing thin serous fluid and are 6Brunicardi_Ch31_p1345-p1392.indd


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Surgery_Schwartz. trauma (seroma or biloma), infection (pyogenic or parasitic), or neoplastic disease. Congenital cysts are usually simple cysts containing thin serous fluid and are 6Brunicardi_Ch31_p1345-p1392.indd 137420/02/19 2:36 PM 1375LIVERCHAPTER 31reported to occur in 5% to 14% of the population, with higher prevalence in women. In most cases, congenital cysts are differ-entiated from secondary cysts (infectious or neoplastic origin) in that they have a well-defined thin wall and no solid component and are filled with homogeneous, clear fluid. For benign solid liver lesions, the differential diagnosis includes hemangioma, adenoma, FNH, and bile duct hamartoma.HemangiomaHemangiomas (also referred to as hemangiomata) are the most common solid benign masses that occur in the liver. They con-sist of large endothelial-lined vascular spaces and represent congenital vascular lesions that contain fibrous tissue and small blood vessels that eventually grow. They are predominantly seen in women and


Surgery_Schwartz

Surgery_Schwartz. of large endothelial-lined vascular spaces and represent congenital vascular lesions that contain fibrous tissue and small blood vessels that eventually grow. They are predominantly seen in women and occur in 2% to 20% of the population. They can range from small (≤1 cm) to giant cavernous hemangiomas (10 to 25 cm). Most hemangiomas are discovered incidentally with little clinical consequence. However, large lesions can cause symptoms as a result of compression of adjacent organs or intermittent thrombosis, which in turn results in further expan-sion of the lesion. Spontaneous rupture (bleeding) is rare, but surgical resection can be considered if the patient is symptom-atic. Resection can be accomplished by enucleation or formal hepatic resection, depending on the location and involvement of intrahepatic vascular structures and hepatic ducts.The majority of hemangiomas can be diagnosed by liver imaging studies. On biphasic contrast CT scan, large hemangio-mas show asymmetrical


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Surgery_Schwartz. of intrahepatic vascular structures and hepatic ducts.The majority of hemangiomas can be diagnosed by liver imaging studies. On biphasic contrast CT scan, large hemangio-mas show asymmetrical nodular peripheral enhancement that is isodense with large vessels and exhibit progressive centripetal enhancement fill-in over time (Fig. 31-18). On MRI, hemangio-mas are hypointense on T1-weighted images and hyperintense on T2-weighted images.76 With gadolinium enhancement, hem-angiomas show a pattern of peripheral nodular enhancement similar to that seen on contrast CT scans. Caution should be exercised in ordering a liver biopsy if the suspected diagnosis is hemangioma because of the risk of bleeding from the biopsy site, especially if the lesion is at the edge of the liver.AdenomaHepatic adenomas are benign solid neoplasms of the liver. They are most commonly seen in premenopausal women older than 30 years of age and are typically solitary, although multiple adenomas also can occur. Prior or


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Surgery_Schwartz. are benign solid neoplasms of the liver. They are most commonly seen in premenopausal women older than 30 years of age and are typically solitary, although multiple adenomas also can occur. Prior or current use of estrogens (oral contraceptives) is a clear risk factor for development of liver adenomas, although they can occur even in the absence of oral contraceptive use. On gross examination, they appear soft and encapsulated and are tan to light brown. Histologically, adeno-mas lack bile duct glands and Kupffer cells, have no true lobules, and contain hepatocytes that appear congested or vacuolated due to glycogen deposition. On CT scan, adenomas usually have Figure 31-18. Computed tomographic scans showing classic appearance of benign liver lesions. Focal nodular hyperplasia (FNH) is hyper-vascular on arterial phase, isodense to liver on venous phase, and has a central scar (upper panels). Adenoma is hypovascular (lower left panel). Hemangioma shows asymmetrical peripheral


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Surgery_Schwartz. is hyper-vascular on arterial phase, isodense to liver on venous phase, and has a central scar (upper panels). Adenoma is hypovascular (lower left panel). Hemangioma shows asymmetrical peripheral enhancement (lower right panel).Brunicardi_Ch31_p1345-p1392.indd 137520/02/19 2:36 PM 1376SPECIFIC CONSIDERATIONSPART IIsharply defined borders and can be confused with metastatic tumors. With venous phase contrast, they can look hypodense or isodense in comparison with background liver, whereas on arterial phase contrast, subtle hypervascular enhancement often is seen (see Fig. 31-18). On MRI scans, adenomas are hyper-intense on T1-weighted images and enhance early after gado-linium injection. With the use of liver-specific MRI contrast agents such as gadoxetate (Eovist or Primovist, Bayer-Schering, Berlin, Germany), hepatic adenomas can be better distinguished from FNH by their enhancement characteristics during the hepa-tobiliary phase of imaging. The new MRI contrast agent,


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Surgery_Schwartz. Bayer-Schering, Berlin, Germany), hepatic adenomas can be better distinguished from FNH by their enhancement characteristics during the hepa-tobiliary phase of imaging. The new MRI contrast agent, gado-benate dimeglumine (MultiHance, Bracco Diagnostics, Milan, Italy), is eliminated through both renal and biliary excretion. Therefore, liver lesions that contain hepatocytes with intact bili-ary excretion mechanism will take up this contrast agent and be easily distinguished from lesions that do not. This contrast agent has improved our ability to differentiate hepatic adenoma from FNH with a high degree of accuracy.Hepatic adenomas carry a significant risk of spontaneous rupture with intraperitoneal bleeding. The clinical presentation may be abdominal pain, and in 10% to 25% of cases, hepatic adenomas present with spontaneous intraperitoneal hemorrhage. Hepatic adenomas also have a risk of malignant transformation to a well-differentiated HCC. Therefore, it usually is recom-mended that


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Surgery_Schwartz. adenomas present with spontaneous intraperitoneal hemorrhage. Hepatic adenomas also have a risk of malignant transformation to a well-differentiated HCC. Therefore, it usually is recom-mended that large hepatic adenomas (>4–5 cm) be surgically resected.Focal Nodular HyperplasiaFNH is a solid, benign lesion of the liver believed to be a hyper-plastic response to an anomalous artery. Similar to adenomas, they are more common in women of childbearing age, although the link to oral contraceptive use is not as clear as with adeno-mas. A good-quality biphasic CT scan usually is diagnostic of FNH, on which such lesions appear well circumscribed with a typical central scar (see Fig. 31-18). They show intense homo-geneous enhancement on arterial phase contrast images and are often isodense or invisible compared with background liver on the venous phase. On MRI scans, FNH lesions are hypoin-tense on T1-weighted images and isointense to hyperintense on T2-weighted images. After gadolinium


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Surgery_Schwartz. invisible compared with background liver on the venous phase. On MRI scans, FNH lesions are hypoin-tense on T1-weighted images and isointense to hyperintense on T2-weighted images. After gadolinium administration, lesions are hyperintense but become isointense on delayed images. The fibrous septa extending from the central scar are also more readily seen with MRI. Unlike adenomas, FNH lesions usually do not rupture spontaneously and have no significant risk of malignant transformation. Therefore, the management of FNH is usually reassurance and prospective observation irrespective of size. Surgical resection can be recommended, however, when patients are symptomatic or when hepatic adenoma or HCC can-not be definitively excluded. Oral contraceptive or estrogen use should be stopped when either FNH or adenoma is diagnosed.Bile Duct HamartomaBile duct hamartomas are typically small liver lesions, 2 to 4 mm in size, visualized on the surface of the liver at laparotomy. They are firm,


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Surgery_Schwartz. either FNH or adenoma is diagnosed.Bile Duct HamartomaBile duct hamartomas are typically small liver lesions, 2 to 4 mm in size, visualized on the surface of the liver at laparotomy. They are firm, smooth, and whitish yellow in appearance. They can be difficult to differentiate from small metastatic lesions, and excisional biopsy often is required to establish the diagnosis.MALIGNANT LIVER TUMORSMalignant tumors in the liver can be classified as primary (cancers that originate in the liver) or metastatic (cancers that spread to the liver from an extrahepatic primary site) (see Table 31-6). Primary cancers in the liver that originate from hepato-cytes are known as hepatocellular carcinomas (HCCs or hepa-tomas), whereas cancers arising in the bile ducts are known as cholangiocarcinomas.In the United States, approximately 150,000 new cases of colorectal cancer are diagnosed each year, and the majority of patients (approximately 60%) will develop hepatic metas-tases over their lifetime.


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Surgery_Schwartz. the United States, approximately 150,000 new cases of colorectal cancer are diagnosed each year, and the majority of patients (approximately 60%) will develop hepatic metas-tases over their lifetime. Hence, the most common tumor seen in the liver is metastatic colorectal cancer. This compares with approximately 30,000 new cases of HCC diagnosed annually in the United States. Interestingly, in a Western series of 1000 con-secutive new liver cancer patients seen at a university medical center, 47% had HCC, 17% had colorectal cancer metastases, 11% had cholangiocarcinomas, 7% had neuroendocrine metas-tases, and 18% had other tumors.77 Although these figures do not reflect the incidence or prevalence of these liver cancers, they are indicative of referral patterns in a tertiary academic medical center with a large liver transplantation team and active hepatology clinic.Hepatocellular CarcinomaHCC is the fifth most common malignancy worldwide, with an estimated 750,000 new cases diagnosed


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Surgery_Schwartz. center with a large liver transplantation team and active hepatology clinic.Hepatocellular CarcinomaHCC is the fifth most common malignancy worldwide, with an estimated 750,000 new cases diagnosed annually. Because of its high fatality, it is the third most common cause of cancer death worldwide.78 Major risk factors are viral hepatitis (B or C), alcoholic cirrhosis, hemochromatosis, and NASH. In Asia, the risk is as high as 35 to 117 per 100,000 persons per year, whereas in the United States, the risk is only 7 per 100,000 per-sons per year.78 Although cirrhosis is not present in all cases, it has been estimated to be present 70% to 90% of the time. In a person with cirrhosis, the annual conversion rate to HCC is 2% to 6%.79 In patients with chronic HCV infection, cirrhosis usually is present before the HCC develops; however, in cases of hepatitis B virus infection, HCC tumors can occur before the onset of cirrhosis. HCCs are typically hypervascular with blood supplied predominantly


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Surgery_Schwartz. before the HCC develops; however, in cases of hepatitis B virus infection, HCC tumors can occur before the onset of cirrhosis. HCCs are typically hypervascular with blood supplied predominantly from the hepatic artery. Thus, the lesion often appears hypervascular during the arterial phase of CT studies (Fig. 31-19) and relatively hypodense during the delayed phases due to early washout of the contrast medium by the arterial blood. MRI imaging also is effective in character-izing HCC. HCC is variable on T1-weighted images and usu-ally hyperintense on T2-weighted images. As with contrast CT, HCC enhances in the arterial phase after gadolinium injection because of its hypervascularity and becomes hypointense in the delayed phases due to contrast washout. HCC has a tendency to invade the portal vein, and the presence of an enhancing portal vein thrombus is highly suggestive of HCC.The treatment of HCC is complex and is best managed by a multidisciplinary liver transplant team. A complete


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Surgery_Schwartz. vein, and the presence of an enhancing portal vein thrombus is highly suggestive of HCC.The treatment of HCC is complex and is best managed by a multidisciplinary liver transplant team. A complete algorithm for the evaluation and management of HCC is shown in Fig. 31-20. For patients without cirrhosis who develop HCC, resection is the treatment of choice. For patients with Child’s class A cirrhosis with preserved liver function and no portal hypertension, resection also is considered. If resection is not possible because of poor liver function and the HCC meets transplant criteria (discussed later), liver transplantation is the treatment of choice.80,81The Barcelona-Clinic Liver Cancer Group has refined its HCC management strategy and has developed the American Association for the Study of Liver Diseases Practice Guidelines.82 Management guidelines vary slightly in Asia, Europe, the 7Brunicardi_Ch31_p1345-p1392.indd 137620/02/19 2:36 PM 1377LIVERCHAPTER 31United States, and


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Surgery_Schwartz. of Liver Diseases Practice Guidelines.82 Management guidelines vary slightly in Asia, Europe, the 7Brunicardi_Ch31_p1345-p1392.indd 137620/02/19 2:36 PM 1377LIVERCHAPTER 31United States, and other countries based in part on availability of organ donors for liver transplantation. Living donor liver trans-plantation also is an alternative for patients with HCC awaiting transplantation to avoid dropout as a candidate for cadaveric donor liver transplantation due to tumor progression.81 Specific treatment options are described in the next section.CholangiocarcinomaCholangiocarcinoma, or bile duct cancer, is the second most common primary malignancy of the liver. Cholangiocarcinoma is an adenocarcinoma of the bile ducts; it forms in the biliary epithelial cells and can be subclassified into peripheral (intra-hepatic) bile duct cancer and central (extrahepatic) bile duct cancer. Extrahepatic bile duct cancer can be located distally or proximally. When proximal, it is referred to as a


Surgery_Schwartz

Surgery_Schwartz. peripheral (intra-hepatic) bile duct cancer and central (extrahepatic) bile duct cancer. Extrahepatic bile duct cancer can be located distally or proximally. When proximal, it is referred to as a hilar chol-angiocarcinoma (Klatskin’s tumor). Hilar cholangiocarcinoma originates in the wall of the bile duct at the hepatic duct conflu-ence and usually presents with obstructive jaundice rather than an actual liver mass. In contrast, a peripheral (or intrahepatic) cholangiocarcinoma represents a tumor mass within a hepatic lobe or at the periphery of the liver. A biopsy specimen from the cholangiocarcinoma will show adenocarcinoma, but patholo-gists are often unable to differentiate metastatic adenocarcinoma to the liver from primary bile duct adenocarcinoma. Therefore, a search for a primary site should be undertaken in cases in which an incidentally discovered liver lesion is proven to be an adenocarcinoma on biopsy.Hilar cholangiocarcinoma is difficult to diagnose and typi-cally


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Surgery_Schwartz. site should be undertaken in cases in which an incidentally discovered liver lesion is proven to be an adenocarcinoma on biopsy.Hilar cholangiocarcinoma is difficult to diagnose and typi-cally presents as a stricture of the proximal hepatic duct causing painless jaundice. It preferentially grows along the length of the bile ducts, often involving the periductal lymphatics with frequent lymph node metastases. Surgical resection offers the only chance for cure of cholangiocarcinoma.83 The location and extent of tumor dictate the operative approach. In one series of 225 patients with hilar cholangiocarcinoma, 65 (29%) were deemed to have unresectable tumors by initial imaging.84 Of the remaining 160 patients who underwent exploratory surgery with curative intent, 80 (50%) were found to have inoperable tumors. Histologically negative margins, concomitant hepatic resection, and well-differentiated tumor histology were associ-ated with improved outcome after resection. In another series of


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Surgery_Schwartz. inoperable tumors. Histologically negative margins, concomitant hepatic resection, and well-differentiated tumor histology were associ-ated with improved outcome after resection. In another series of 61 patients undergoing surgical exploration for hilar cholangio-carcinoma, the 5-year actuarial survival rates for an R0 or R1 resection were 45% and 26%, respectively.85 In a large series reported by Nagino and colleagues, 132 patients with hilar chol-angiocarcinoma underwent extended hepatectomy with resec-tion of the caudate lobe and extrahepatic bile duct, and/or portal vein resection (n = 63) after portal vein embolization.86 The 3and 5-year survival rates were 41.7% and 26.8%, respectively.In the absence of associated primary sclerosing cholangi-tis (PSC), surgical resection is the treatment of choice for hilar cholangiocarcinoma. However, approximately 10% of patients with cholangiocarcinoma have PSC.87 Furthermore, cholangio-carcinoma in the setting of PSC is frequently


Surgery_Schwartz

Surgery_Schwartz. the treatment of choice for hilar cholangiocarcinoma. However, approximately 10% of patients with cholangiocarcinoma have PSC.87 Furthermore, cholangio-carcinoma in the setting of PSC is frequently multicentric and often is associated with underlying liver disease, with eventual cirrhosis and portal hypertension. As a result, experience has shown that resection of cholangiocarcinoma in patients with PSC yields dismal results. This led transplant centers to con-sider OLT for patients with hilar cholangiocarcinoma. The ini-tial results of transplantation were disappointing, however, with high recurrence and overall 3-year survival rates of <30%.88Because the growth of hilar cholangiocarcinoma indicates that this disease spreads in a locoregional manner, a rationale for the use of neoadjuvant chemoradiation was developed by the transplant team at the University of Nebraska in the late 1980s. This was adapted in 1993 by the transplant team at the Mayo Clinic, which led to the current Mayo


Surgery_Schwartz

Surgery_Schwartz. chemoradiation was developed by the transplant team at the University of Nebraska in the late 1980s. This was adapted in 1993 by the transplant team at the Mayo Clinic, which led to the current Mayo Clinic protocol.89 The pretransplant Mayo protocol consists of external-beam radiation therapy plus a protracted course of intravenous 5-fluorouracil followed by iridium-192 brachytherapy.90 Patients then undergo an abdominal exploration with staging. If findings are negative, patients are given capecitabine for 2 of every 3 weeks until transplantation. Even after restaging with CT/MRI and endo-scopic ultrasonography, approximately 15% to 20% of patients will have positive findings for tumor on abdominal Figure 31-19. Computed tomographic (CT) images of hepato-cellular carcinoma (HCC) and peripheral cholangiocarcinoma. CT scans reveal a large (upper panel) and small (middle panel) hypervascular HCC. A hypovascular left lobe peripheral cholangio-carcinoma (CholangioCA) is also shown (lower


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Surgery_Schwartz. cholangiocarcinoma. CT scans reveal a large (upper panel) and small (middle panel) hypervascular HCC. A hypovascular left lobe peripheral cholangio-carcinoma (CholangioCA) is also shown (lower panel).Brunicardi_Ch31_p1345-p1392.indd 137720/02/19 2:36 PM 1378SPECIFIC CONSIDERATIONSPART IIexploration.87,90 The 5-year survival rate for those undergoing transplantation for cholangiocarcinoma at the Mayo Clinic is approximately 70% and compares favorably with the rate for resection.87,90 Current eligibility criteria for this Mayo Clinic protocol include unresectable hilar cholangiocarcinoma or hilar cholangiocarcinoma with PSC. The tumor must have a radial dimension of ≤3 cm with no intrahepatic or extrahepatic metastases, and the patient must not have undergone prior radiation therapy or transperitoneal biopsy.90 Many centers have adopted similar protocols with comparable results.91Peripheral, or intrahepatic, cholangiocarcinoma is less common than hilar cholangiocarcinoma. In a


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Surgery_Schwartz. or transperitoneal biopsy.90 Many centers have adopted similar protocols with comparable results.91Peripheral, or intrahepatic, cholangiocarcinoma is less common than hilar cholangiocarcinoma. In a series of 53 patients at Memorial Sloan-Kettering Cancer Center who underwent surgical exploration for a diagnosis of intrahepatic cholangiocarcinoma, 33 (62%) were found to have resectable tumors.92 Actuarial 3-year survival for patients undergoing resection was 55%. Factors predictive of poor survival included vascular invasion, histologically positive margins, and multiple tumors. In a large series in Taiwan, 373 patients with peripheral cholangiocarcinoma underwent surgical treatment from 1977 to 2001. Absence of mucobilia, nonpapillary tumor type, tumor of advanced stage, nonhepatectomy, and lack of postoperative chemotherapy were five independent prognostic factors that adversely affected overall survival.93 Liver transplantation has been performed for peripheral


Surgery_Schwartz

Surgery_Schwartz. nonhepatectomy, and lack of postoperative chemotherapy were five independent prognostic factors that adversely affected overall survival.93 Liver transplantation has been performed for peripheral cholangiocarcinoma94; however, currently all but one center in the United States have eschewed this approach because of organ shortages and relatively high recurrence rates.Gallbladder CancerGallbladder cancer is a rare aggressive tumor with a very poor prognosis. Over 90% of patients have associated cholelithia-sis. In one study examining the mode of presentation over a 10-year period from 1990 to 2000 in 44 patients diagnosed with gallbladder cancer, the diagnosis was found to be made preoperatively in 57%, intraoperatively in 11%, and inciden-tally after cholecystectomy in 32%.95 Surgical approaches can be classified into (a) reoperation for an incidental finding of gallbladder cancer after cholecystectomy, and (b) radical resec-tion in patients with advanced disease. The results are


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Surgery_Schwartz. approaches can be classified into (a) reoperation for an incidental finding of gallbladder cancer after cholecystectomy, and (b) radical resec-tion in patients with advanced disease. The results are dismal for radical resection in patients with advanced disease and positive hilar lymph nodes.96,97 For incidental gallbladder can-cer beyond stage T1, reoperation with central liver resection, hilar lymphadenectomy, and evaluation of cystic duct stump is most commonly performed.98,99 The role of formal lobectomy or extended lobectomy as well as common bile duct resection is more controversial. In a single-center study of 23 patients undergoing attempted curative treatment by surgical resec-tion, survival was 85% at 1 year, 63% at 2 years, and 55% at 3 years.99 In a multicenter study encompassing 115 patients with incidentally discovered gallbladder cancer who underwent re-resection,98 residual disease in the liver was identified in 46% of patients (0% of those with stage T1 disease, 10%


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Surgery_Schwartz. 115 patients with incidentally discovered gallbladder cancer who underwent re-resection,98 residual disease in the liver was identified in 46% of patients (0% of those with stage T1 disease, 10% of those with T2 tumors, and 36% of those with T3 disease). T stage also was associated with the risk of metastasis to locoregional lymph nodes (lymph node metastasis for T1 of 13%; for T2, 31%; and for T3, 46%). In another study, a German registry of incidental gallbladder cancer identified 439 patients. Patients with tumors staged as T2 or T3 after cholecystectomy had better survival if they underwent reoperation than if they were managed with observation.100 Hence, reoperation should be considered for all patients who have T2 or T3 tumors or for whom the accuracy of staging is in question.Metastatic Colorectal CancerOver 50% to 60% of patients diagnosed with colorectal cancer will develop hepatic metastases during their lifetime. Resection for hepatic metastases has been a routine part of


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Surgery_Schwartz. Colorectal CancerOver 50% to 60% of patients diagnosed with colorectal cancer will develop hepatic metastases during their lifetime. Resection for hepatic metastases has been a routine part of treatment for 8ResectionNoncirrhotic/Child’s ASingle lesionNo metastasisOLTx evaluation1 lesion ˜5 cm3 lesions ˜3 cmChild’s A/B/CNo gross vasc. invasionNo metastasisNot Tx candidateComorbid factors°4 lesionsGross vasc. invasionLN (+) or metastasisLDLT ?Suitable donorPalliative careChild’s CBili °3 HCC IdentifiedResection candidate?Transplant candidate?YesYesNoSorafenibYesYesNoOLTxClinicaltrialsNeoadjuvant therapyRFA/TACE/90 YttriumUNOS list (cadaver)MELD score (? >3 mos)Perc/lap. RFASingle lesion<5 cmChild’s A/BTace/90 YttriumMulti-focal >5 cmChild’s A/B/CBili <3NewagentsFigure 31-20. Algorithm for the management of hepatocellular carcinoma (HCC). The treatment algorithm for HCC begins with determining whether the patient is a resection candidate or liver transplant candidate. Bili = bilirubin


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Surgery_Schwartz. the management of hepatocellular carcinoma (HCC). The treatment algorithm for HCC begins with determining whether the patient is a resection candidate or liver transplant candidate. Bili = bilirubin level (in milligrams per deciliter); Child’s = Child-Turcotte-Pugh class; lap = laparoscopic; LDLT = living-donor liver transplantation; LN = lymph node; MELD = Model for End-Stage Liver Disease; OLTx = orthotopic liver transplantation; Perc = percutaneous; RFA = radiofrequency ablation; TACE = transarterial chemoemboli-zation; Tx = transplantation; UNOS = United Network for Organ Sharing; vasc. = vascular.Brunicardi_Ch31_p1345-p1392.indd 137820/02/19 2:36 PM 1379LIVERCHAPTER 31colorectal cancer since the publication of a large single-center experience demonstrating its safety and efficacy.101 Predictors of poor outcome in that study included node-positive primary, disease-free interval <12 months, more than one tumor, tumor size >5 cm, and carcinoembryonic antigen level >200 ng/mL.


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Surgery_Schwartz. Predictors of poor outcome in that study included node-positive primary, disease-free interval <12 months, more than one tumor, tumor size >5 cm, and carcinoembryonic antigen level >200 ng/mL. Traditional teaching suggested that hepatic resection for meta-static colorectal cancer to the liver, if technically feasible, should be performed only for fewer than four metastases.102 However, later studies challenged this paradigm. In a series of 235 patients who underwent hepatic resection for metastatic colorectal cancer, the 10-year survival rate of patients with four or more nodules was 29%, nearly comparable to the 32% sur-vival rate of patients with only a solitary tumor metastasis.103 In the Memorial Sloan-Kettering Cancer Center series of 98 patients with four or more colorectal hepatic metastases who underwent resection between 1998 and 2002, the 5-year actu-arial survival was 33%.104 Furthermore, improved chemothera-peutic regimens and surgical techniques have produced aggressive


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Surgery_Schwartz. metastases who underwent resection between 1998 and 2002, the 5-year actu-arial survival was 33%.104 Furthermore, improved chemothera-peutic regimens and surgical techniques have produced aggressive strategies for the management of this disease. Many groups now consider volume of future liver remnant and the health of the background liver, and not actual tumor number, as the primary determinants in selection for an operative approach.105,106 Hence, resectability is no longer defined by what is actually removed, but indications for hepatic resection now center on what will remain after resection.107 Use of neo-adjuvant chemotherapy, portal vein embolization, two-stage hepatectomy, simultaneous ablation, and resection of extrahepatic tumor in select patients have increased the number of patients eligible for a surgical approach.108,109Neuroendocrine TumorsHepatic metastases from neuroendocrine tumors have a protracted natural history and commonly are associated with debilitating


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Surgery_Schwartz. of patients eligible for a surgical approach.108,109Neuroendocrine TumorsHepatic metastases from neuroendocrine tumors have a protracted natural history and commonly are associated with debilitating endocrinopathies. Several groups have advocated an aggressive surgical approach of debulking surgery, both to control symp-toms and to extend survival.110,111 In a series of 170 patients undergoing resection of hepatic metastases from neuroendocrine tumors between 1977 and 1998 at the Mayo Clinic, overall sur-vival was 61% and 35% at 5 and 10 years, respectively.112 There was no difference in survival between patients with carcinoid tumors and those with islet cell tumors. Major hepatectomy was performed in 91 patients (54%), and recurrence rate was 84% at 5 years. Belghiti’s group has described a two-stage strategy used in 41 patients with a primary neuroendocrine tumor and synchronous bilobar liver metastases.113 In the first stage, the primary tumor is resected and limited resection of


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Surgery_Schwartz. a two-stage strategy used in 41 patients with a primary neuroendocrine tumor and synchronous bilobar liver metastases.113 In the first stage, the primary tumor is resected and limited resection of metastases in the left hemiliver, combined with right portal vein ligation, is performed. After 8 weeks of hypertrophy, a right hepatec-tomy or extended right hepatectomy (also referred to as a right trisectionectomy; resection of Couinaud’s segments IV, V, VI, VII, and VIII of the liver) is performed.113 In patients treated using this strategy, the 2-, 5-, and 8-year Kaplan-Meier over-all survival rates were 94%, 94%, and 79%, respectively, and disease-free survival rates were 85%, 50%, and 26%, respec-tively. Because systemic therapy has had little success in the treatment of advanced tumors, a broader approach using multi-modal therapy has been used to increase survival and improve hormone-related symptoms. These therapies include radiofre-quency or microwave ablation and intra-arterial


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Surgery_Schwartz. a broader approach using multi-modal therapy has been used to increase survival and improve hormone-related symptoms. These therapies include radiofre-quency or microwave ablation and intra-arterial therapy with chemoembolization or radioembolization (yttrium-90). Some centers perform liver transplantation for selected patients (carci-noid histology; primary tumor removed with curative resection; primary tumor drained by portal system; ≤50% hepatic paren-chyma involved; good response or stable disease for at least 6 months during pretransplantation period; and age 55 years or younger), although this is not routine.114Other Metastatic TumorsNearly every cancer has the propensity to metastasize to the liver. Historically, enthusiasm was low for resecting metastases other than those from a colorectal cancer primary. This was due in part to the recognition that many other primary cancers (such as breast cancer) represent a systemic disease when liver metas-tases are present. However, more


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Surgery_Schwartz. cancer primary. This was due in part to the recognition that many other primary cancers (such as breast cancer) represent a systemic disease when liver metas-tases are present. However, more recent studies have shown acceptable 5-year survival rates in the 20% to 40% range for resection of hepatic metastases from breast, renal, and other GI tumors.115,116 In a large study of hepatic resection for non-colorectal, nonendocrine liver metastases in 1452 patients, neg-ative prognostic factors were nonbreast origin, age >60 years, disease-free interval of <12 months, need for major hepatec-tomy, performance of R2 resection, and presence of extrahe-patic metastases.115TREATMENT OPTIONS FOR LIVER CANCERIn general, the major treatment options for liver cancer can be categorized as shown in Table 31-7. The decision making for any given patient is complex and is best managed by a multidis-ciplinary liver tumor board. The treatments listed in Table 31-7 are not mutually exclusive; the important


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Surgery_Schwartz. 31-7. The decision making for any given patient is complex and is best managed by a multidis-ciplinary liver tumor board. The treatments listed in Table 31-7 are not mutually exclusive; the important point is to select the most appropriate initial treatment after a complete evaluation. In general, surveillance imaging (CT or MRI) is performed every 3 to 4 months during the first year after diagnosis to observe for response, progression, or recurrence. The treatment plan is indi-vidualized and modified according to the response of the patient.Hepatic ResectionFor primary liver cancers or hepatic metastases, hepatic resection is the gold standard and treatment of choice. Although there are anecdotal reports of long-term survival after ablation and other regional liver therapies, liver resection remains the only real option for cure. For HCC in the setting of cirrhosis, liver trans-plantation also offers the potential for long-term survival, albeit with the consequences of


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Surgery_Schwartz. liver resection remains the only real option for cure. For HCC in the setting of cirrhosis, liver trans-plantation also offers the potential for long-term survival, albeit with the consequences of immunosuppression. Hepatic resection 9Table 31-7Treatment options for liver cancerHepatic resectionLiver transplantationAblation techniquesRadiofrequency ablation• Ethanol ablation• Cryoablation• Microwave ablationRegional liver therapies• Chemoembolization/embolization• Hepatic artery pump chemoperfusion• Internal radiation therapy (yttrium-90 internal radiation)External-beam radiation therapy• Stereotactic radiosurgery (CyberKnife, Trilogy, Synergy)• Intensity-modulated radiation therapySystemic chemotherapyMultimodality approachBrunicardi_Ch31_p1345-p1392.indd 137920/02/19 2:36 PM 1380SPECIFIC CONSIDERATIONSPART IIalso has been advocated for HCC in select patients with cirrho-sis before secondary liver transplantation, although not without some controversy.117 Many large series of


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Surgery_Schwartz. CONSIDERATIONSPART IIalso has been advocated for HCC in select patients with cirrho-sis before secondary liver transplantation, although not without some controversy.117 Many large series of patients undergoing major hepatectomy now report mortality rates of <5%.118-121 Pre-viously, a 1-cm tumor margin was considered desirable; how-ever, recent studies have reported comparable survival rates with smaller margins.122-124 Technical innovation in liver surgery and a better understanding of perioperative care have even allowed surgeons to perform resections in cases with IVC involvement with extracorporeal liver surgery.125 The technical aspects of anatomic hepatic lobectomies are described later.Liver TransplantationThe rationale supporting OLT for HCC includes the fact that most HCCs (>80%) arise in the setting of cirrhosis.88,126 The cirrhotic liver often does not have enough reserve to tolerate a formal resection. Also, HCC tumors are commonly multifo-cal and are underestimated by


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Surgery_Schwartz. arise in the setting of cirrhosis.88,126 The cirrhotic liver often does not have enough reserve to tolerate a formal resection. Also, HCC tumors are commonly multifo-cal and are underestimated by current CT or MRI imaging.127 Furthermore, recurrence rates are high at 5 years after resec-tion (>50%). Hence, OLT is an appealing treatment because it removes both the cancer and the cirrhotic liver that leads to can-cer. More than 7000 liver transplantations are performed each year in the United States, with 1-year survival rates approaching 90%. In May 2017, approximately 14,463 patients were on the waiting list for liver transplantation.128Initial series of OLT for HCC reported in the 1990s included advanced cases of HCC, and the 5-year survival rates were only 20% to 50%.88 This compared poorly with overall 5-year survival rates of 70% to 75% for OLT in the Organ Pro-curement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database. Mazzaferro and col-leagues at


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Surgery_Schwartz. with overall 5-year survival rates of 70% to 75% for OLT in the Organ Pro-curement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database. Mazzaferro and col-leagues at Milan subsequently showed that survival rates were markedly improved when OLT was limited to patients with early-stage HCC (stage I or stage II) with one tumor ≤5 cm, or up to three tumors no larger than 3 cm, along with the absence of gross vascular invasion or extrahepatic spread.129 Multiple studies have validated these findings, and many groups have proposed an expansion of the Milan criteria.81As noted previously, the 6to 40-point MELD score was adopted by OPTN/UNOS in 2002 for allocation of deceased donor liver organs in the United States. In an attempt to pri-oritize patients with preserved liver function and progressive HCC, patients with stage II HCC are allocated exception points (currently 28 MELD points which activates 6 months after liver transplant listing, increasing every 3


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Surgery_Schwartz. liver function and progressive HCC, patients with stage II HCC are allocated exception points (currently 28 MELD points which activates 6 months after liver transplant listing, increasing every 3 months and capping at 34 points as long as they continue to meet transplant criteria). This allocation has had a positive effect for HCC liver transplant can-didates, leading to decreased waiting list dropout and increased transplant rates with excellent long-term outcomes.130 The goal is to better equate death rates on the liver transplant waiting list for patients with stage I or stage II HCC with rates for patients with chronic liver disease without HCC. Although indications for liver transplantation have increased, the supply of donor liv-ers has failed to keep pace with the numbers of potential recipi-ents. A partial solution has been the use of living donor grafts. This is especially true in Asia where the incidence of HCC is high and the rate of cadaveric donation is low. Living donor


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Surgery_Schwartz. recipi-ents. A partial solution has been the use of living donor grafts. This is especially true in Asia where the incidence of HCC is high and the rate of cadaveric donation is low. Living donor grafts include right and left lobes, as well as dual grafts from separate donors to provide adequate hepatic mass to the recipi-ent. The use of living donor grafts also allows for transplant programs to push the boundaries by accepting patients beyond the Milan criteria with good results.112Radiofrequency AblationIn 1891, d’Arsonval discovered that radiofrequency (RF) waves delivered as an alternating electric current (>10 kHz) could pass through living tissue without causing pain or neuromuscular excitation. The resistance of the tissue to the rapidly alternating current produced heat. This discovery contributed to the devel-opment of the surgical application of electrocautery. In 1908, Beer used RF coagulation to destroy urinary bladder tumors. Cushing and Bovie later applied RF ablation to


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Surgery_Schwartz. contributed to the devel-opment of the surgical application of electrocautery. In 1908, Beer used RF coagulation to destroy urinary bladder tumors. Cushing and Bovie later applied RF ablation to intracranial tumors. In 1961, Lounsberry studied the histologic changes of the liver after RF ablation (RFA) in animal models. He found that RF caused local tissue destruction with uniform necrosis. In the early 1990s, two groups proposed that RFA can be an effective method for destroying unresectable malignant liver tumors.132,133 Both groups found that RFA produced lesions with well-demarcated areas of necrosis without viable tumor cells present. Clinical reports after short-term follow-up sug-gested that RFA was safe and effective in the treatment of liver tumors.134-136 However, Abdalla and colleagues exam-ined data for 358 consecutive patients with colorectal liver metastases treated with curative intent over a 10-year period (1992 to 2002).137 Liver-only recurrence after RFA was four


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Surgery_Schwartz. colleagues exam-ined data for 358 consecutive patients with colorectal liver metastases treated with curative intent over a 10-year period (1992 to 2002).137 Liver-only recurrence after RFA was four times the rate after resection (44% vs. 11% of patients), and RFA alone or in combination with resection did not provide survival rates comparable to those with resection alone. None-theless, RFA remains a common procedure that can be per-formed by a percutaneous, minimally invasive laparoscopic, or open approach.138,139 It also has been used successfully to ablate small HCCs as a bridge to liver transplantation.140 Results were reported for the first randomized clinical trial involving RFA treatment for HCC in 291 Chinese patients with three or fewer HCC tumors ranging in size from 3 to 7.5 cm.141 Patients were randomly assigned to treatment arms of RFA alone (n = 100), transarterial chemoembolization (TACE) alone (n = 95), or combined TACE plus RFA (n = 96). At a median follow-up of 28.5


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Surgery_Schwartz. Patients were randomly assigned to treatment arms of RFA alone (n = 100), transarterial chemoembolization (TACE) alone (n = 95), or combined TACE plus RFA (n = 96). At a median follow-up of 28.5 months, median survival was 22 months in the RFA group, 24 months in the TACE group, and 37 months in the TACE plus RFA group. Patients treated with TACE plus RFA had sig-nificantly better overall survival than those treated with TACE alone (P <.001) or RFA alone (P <.001). Sucandy and col-leagues examined long-term 5and 10-year overall survival in 320 patients that had hepatic RFA for HCC or colorectal cancer liver metastases (CLM).142 The majority of patients (71%) had a single tumor ablation. Minimum 5-year follow-up was available in 89% patients, with a median follow-up of 115.3 months. In the HCC group, the 5and 10-year overall survivals were 38.5% and 23.4%, respectively, while in the CLM group, the 5and 10-year overall survivals were 27.6% and 15%, respectively.Ethanol Ablation,


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Surgery_Schwartz. In the HCC group, the 5and 10-year overall survivals were 38.5% and 23.4%, respectively, while in the CLM group, the 5and 10-year overall survivals were 27.6% and 15%, respectively.Ethanol Ablation, Cryosurgery, and Microwave AblationPercutaneous ethanol injection has been shown to be a safe and effective treatment for small HCCs.136 The ethanol usually is delivered by percutaneous injection under ultrasound or CT guidance. Percutaneous ethanol injection also is used to treat small HCC tumors as a bridge to liver transplantation in some centers to avoid patient dropout.80 Although cryosurgery was used in the late 1980s and 1990s for ablation of liver tumors, many have abandoned this approach in favor of RFA because of the latter’s fewer side effects and ease of use. Microwave ablation is a thermal ablative technique used in the management of unresectable liver tumors to produce a coagulation necrosis. Brunicardi_Ch31_p1345-p1392.indd 138020/02/19 2:36 PM 1381LIVERCHAPTER 31In a


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Surgery_Schwartz. a thermal ablative technique used in the management of unresectable liver tumors to produce a coagulation necrosis. Brunicardi_Ch31_p1345-p1392.indd 138020/02/19 2:36 PM 1381LIVERCHAPTER 31In a multicenter phase 2 U.S. trial using a 915-MHz micro-wave generator, 87 patients underwent 94 ablation procedures for 224 hepatic tumors.143 Forty-five percent of the procedures were performed using an open approach, 7% laparoscopically, and 48% percutaneously. The average tumor size was 3.6 cm (range, 0.5 to 9.0 cm). At a mean follow-up of 19 months, 47% of the patients were alive with no evidence of disease. Local recurrence at the ablation site occurred in 2.7% of tumors, and regional recurrence occurred in 43% of patients. There were no procedure-related deaths. Further studies are required to define the role of this technology in relation to the other abla-tion options available.Chemoembolization and Hepatic Artery Pump ChemoperfusionChemoembolization is the process of injecting


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Surgery_Schwartz. to define the role of this technology in relation to the other abla-tion options available.Chemoembolization and Hepatic Artery Pump ChemoperfusionChemoembolization is the process of injecting chemotherapeu-tic drugs combined with embolization particles into the hepatic artery that supplies the liver tumor using a percutaneous, trans-femoral approach. It is most commonly used for treatment of unresectable HCC. Three randomized trials and a meta-analysis have shown a survival benefit with chemoembolization.144-147 In a study by Lo and colleagues, 80 Asian patients were randomly assigned to receive either chemoembolization with cisplatin in lipiodol or symptomatic treatment only.144 Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1and 3-year survival of 57% and 26%, respectively) than in the con-trol group (1and 3-year survival of 32% and 3%, respectively). In another randomized trial, a


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Surgery_Schwartz. better in the chemoembolization group (1and 3-year survival of 57% and 26%, respectively) than in the con-trol group (1and 3-year survival of 32% and 3%, respectively). In another randomized trial, a Barcelona group compared chemoembolization with doxorubicin versus supportive care and showed that chemoembolization significantly improved survival.145 Finally, in a large prospective cohort study of 8510 patients with unresectable HCC in Japan who received trans-catheter arterial lipiodol chemoembolization, the 5-year survival rate was 26% and median survival time was 34 months.146 The TACE-related mortality rate after the initial therapy was 0.5%. Complications of TACE include liver dysfunction or liver fail-ure, hepatic abscess, and hepatic artery thrombosis. Multiple studies also have shown promising results for chemoemboliza-tion with drug-eluting beads in treatment of HCC.148In the 1990s, hepatic artery pump chemoperfusion with floxuridine for colorectal cancer metastases to the


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Surgery_Schwartz. shown promising results for chemoemboliza-tion with drug-eluting beads in treatment of HCC.148In the 1990s, hepatic artery pump chemoperfusion with floxuridine for colorectal cancer metastases to the liver was used both for treatment of inoperable disease and in the adjuvant setting.149 However, in the modern era of improved chemothera-peutic options, this treatment modality is seldom used outside of a clinical trial.Yttrium-90 MicrospheresSelective internal radioembolization or transarterial radioem-bolization (TARE) is a promising new treatment modality for patients with inoperable primary or metastatic liver tumors. The treatment is a minimally invasive transcatheter therapy in which radioactive microspheres are infused into the hepatic arteries via a transfemoral percutaneous approach. The yttrium-90 micro-spheres are directly injected into the hepatic artery branches that supply the tumor. Once infused, the microspheres deliver doses of high-energy, low-penetration radiation


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Surgery_Schwartz. The yttrium-90 micro-spheres are directly injected into the hepatic artery branches that supply the tumor. Once infused, the microspheres deliver doses of high-energy, low-penetration radiation selectively to the tumor. The main indications are inoperable HCC150 and colorec-tal cancer hepatic metastases for which systemic chemotherapy has failed.151,152 In a study involving 137 patients with unresect-able chemorefractory liver metastases treated with radioembo-lization, there was a response rate of 42.8% (2.1% complete response, 40.7% partial response) according to World Health Organization criteria.152 One-year survival rate was 47.8%, and 2-year survival rate was 30.9%. Median survival was 457 days for patients with colorectal tumor metastases, 776 days for those with neuroendocrine tumor metastases, and 207 days for those with noncolorectal, nonneuroendocrine tumor metastases. The two products available in the United States are SIR-Spheres (Sirtex, Sydney, Australia) and


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Surgery_Schwartz. tumor metastases, and 207 days for those with noncolorectal, nonneuroendocrine tumor metastases. The two products available in the United States are SIR-Spheres (Sirtex, Sydney, Australia) and TheraSphere (Nordian, Ottawa, Canada).Stereotactic Radiosurgery and Intensity-Modulated Radiation TherapyAlthough stereotactic radiosurgery (with CyberKnife and other systems) is in widespread use for brain and spinal tumors, body application to HCC or metastatic liver tumors has only recently occurred. In a phase 1 study, 31 patients with unresectable HCCs and 10 with unresectable cholangiocarcinomas completed a six-fraction course of stereotactic body radiotherapy.153 The treat-ment was well tolerated, and median survival was 11.7 and 15.0 months for the two groups, respectively. A similar safety profile was observed in a study in the Netherlands.154 Further clinical trials are required to define the future role of stereo-tactic radiosurgery in treatment of HCC and metastatic tumors.


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Surgery_Schwartz. safety profile was observed in a study in the Netherlands.154 Further clinical trials are required to define the future role of stereo-tactic radiosurgery in treatment of HCC and metastatic tumors. Intensity-modulated radiation therapy (IMRT) is another tech-nologic advancement that facilitates the targeted delivery of external-beam radiation. Early clinical data suggested favorable outcomes with IMRT for the treatment of patients with unre-sectable HCC, and ongoing trials are further examining the role of IMRT for these locally advanced tumors.DownstagingIn more advanced-stage patients not eligible for MELD excep-tion points, hepatic-directed therapy including TACE and tumor ablation with radiofrequency, microwave, and ethanol ablation have been found to be effective in shrinking tumors to meet Milan criteria (downstaging). Multiple centers have used down-staging to allow for OLT in patients whose tumors responded and shrank to meet eligibility criteria.155,156Systemic


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Surgery_Schwartz. tumors to meet Milan criteria (downstaging). Multiple centers have used down-staging to allow for OLT in patients whose tumors responded and shrank to meet eligibility criteria.155,156Systemic ChemotherapyChemotherapy has not demonstrated great efficacy in patients with HCC, especially in patients with significant cirrhosis. For treatment of HCC, the multikinase inhibitor sorafenib has shown some efficacy in a phase 3 randomized international multicenter trial. The SHARP trial (Sorafenib HCC Assessment Random-ized Protocol) enrolled 602 patients with Child’s class A cir-rhosis and inoperable HCC. At interim analysis, the trial was discontinued because a survival benefit was found in the treat-ment group. The median overall survival for patients receiv-ing sorafenib was 10.7 months versus 7.9 months for patients in the control arm. Based on these findings, sorafenib received accelerated Food and Drug Administration approval for the treatment of advanced unresectable HCC.157 Future


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Surgery_Schwartz. 7.9 months for patients in the control arm. Based on these findings, sorafenib received accelerated Food and Drug Administration approval for the treatment of advanced unresectable HCC.157 Future studies will likely examine the role of other molecularly targeted agents and combinations of sorafenib with other treatment modalities.HEPATIC RESECTION SURGICAL TECHNIQUESNomenclatureDue to the confusion in language with regard to anatomic descrip-tions of hepatic resections, a common nomenclature was intro-duced at the International Hepato-Pancreato-Biliary Association Brunicardi_Ch31_p1345-p1392.indd 138120/02/19 2:36 PM 1382SPECIFIC CONSIDERATIONSPART IImeeting in Brisbane, Australia, in 2000 (Table 31-8).158,159 The goal was to provide universal terminology for liver anatomy and hepatic resections because there was much overlap among the designations for hepatic lobes, sections, sectors, and segments used by surgeons worldwide (Fig. 31-21). The most common or prevailing anatomic


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Surgery_Schwartz. resections because there was much overlap among the designations for hepatic lobes, sections, sectors, and segments used by surgeons worldwide (Fig. 31-21). The most common or prevailing anatomic pattern was used as the basis for naming liver anatomy, and the surgical procedure nomenclature adopted for hepatic resections was based on the assigned anatomic ter-minology.160 Adoption of a common language should enable hepatic surgeons to better understand and interpret liver surgery publications from different continents and disseminate their knowledge to the next generation of hepatobiliary surgeons. Nonetheless, even today, the literature is full of both old and new liver resection terminology, so the surgeon in training must be familiar with all the various classifications.Techniques and Devices for Dividing the Hepatic ParenchymaHepatic resection surgery has evolved over the past 50 years. A better understanding of liver anatomy and physiology, coupled with improved anesthesia


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Surgery_Schwartz. and Devices for Dividing the Hepatic ParenchymaHepatic resection surgery has evolved over the past 50 years. A better understanding of liver anatomy and physiology, coupled with improved anesthesia techniques and widespread use of intraoperative ultrasound, has led to virtually “bloodless” liver surgery in the modern era (the year 2000 to the present). Innova-tions in technology have expanded the list of liver parenchymal transection devices161-163 and hemostatic agents (Table 31-9). Use of each device or agent has a learning curve, and undoubt-edly every experienced hepatic surgeon has his or her personal preferences.One major trend has been the application of vascular sta-pling devices for division of the hepatic and portal veins.164-166 Based on early reports of successful stapling of extrahepatic Table 31-8Brisbane 2000 liver terminologyOLDER HEPATIC RESECTION TERMINOLOGYBRISBANE 2000 HEPATIC RESECTION TERMINOLOGY Right hepatic lobectomy Left hepatic lobectomy Right hepatic


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Surgery_Schwartz. of extrahepatic Table 31-8Brisbane 2000 liver terminologyOLDER HEPATIC RESECTION TERMINOLOGYBRISBANE 2000 HEPATIC RESECTION TERMINOLOGY Right hepatic lobectomy Left hepatic lobectomy Right hepatic trisegmentectomy Left hepatic trisegmentectomy Left lateral segmentectomy Right posterior lobectomy Caudate lobectomy Right hepatectomy or right hemihepatectomy (V, VI, VII, VIII) Left hepatectomy or left hemihepatectomy (II, III, IV) Right trisectionectomy or extended right hepatectomy (or hemihepatectomy, IV, V, VI, VII, VIII) Left trisectionectomy or extended left hepatectomy (or hemihepatectomy, II, III, IV, V, VIII) Left lateral sectionectomy or bisegmentectomy (II, III) Right posterior sectionectomy (VI, VII) Caudate lobectomy or segmentectomy (I)ALTERNATIVE “SECTOR” TERMINOLOGY Right anterior sectorectomy Right posterior sectorectomy or right lateral sectorectomy Left medial sectorectomy or left paramedian sectorectomy (bisegmentectomy, III, IV) Left lateral sectorectomy


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Surgery_Schwartz. anterior sectorectomy Right posterior sectorectomy or right lateral sectorectomy Left medial sectorectomy or left paramedian sectorectomy (bisegmentectomy, III, IV) Left lateral sectorectomy (segmentectomy, II)IVCRHVMHVVIIVIIIIVaIIVIVIVbIIIFalciform lig.Portal veinIVCLHVIFigure 31-21. Hepatic anatomy. Hepatic segments removed in the formal major hepatic resections are indicated. IVC = inferior vena cava; LHV = left hepatic vein; MHV = middle hepatic vein; RHV = right hepatic vein.Table 31-9Techniques and devices for dividing liver parenchyma and achieving hemostasisBlunt fracture and clipsMonopolar cautery (Bovie)Bipolar cauteryArgon beam coagulatorCUSA ultrasonic dissectorHydro-Jet water-jet dissectorHarmonic Scalpel, AutoSonix ultrasonic transector-coagulatorLigaSure tissue fusion systemSurgRx EnSeal tissue sealing and transection systemGyrus PK cutting forcepsEndovascular staplersTissueLink sealing devicesHabib 4X Laparoscopic sealerInLine bipolar linear coagulatorTopical agents


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Surgery_Schwartz. EnSeal tissue sealing and transection systemGyrus PK cutting forcepsEndovascular staplersTissueLink sealing devicesHabib 4X Laparoscopic sealerInLine bipolar linear coagulatorTopical agents (fibrin glues, Surgicel, Gelfoam, Avitene, Tisseel, Floseal, Crosseal)Brunicardi_Ch31_p1345-p1392.indd 138220/02/19 2:36 PM 1383LIVERCHAPTER 31vessels, stapling devices are now being used in the parenchymal transection phase, which remains a source of potential blood loss due to back bleeding from the middle hepatic vein.167,168 One advantage of the stapling technique is the speed with which the transection can be performed, which minimizes surface bleeding and period of ischemia for the remnant liver. How-ever, a major disadvantage of the stapling technique is the cost of multiple stapler cartridges. This is balanced by the decreased expenses reported with avoidance of ICU admission and blood transfusion, as well as shortened operating room time. Another consideration in the use of staplers


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Surgery_Schwartz. This is balanced by the decreased expenses reported with avoidance of ICU admission and blood transfusion, as well as shortened operating room time. Another consideration in the use of staplers for parenchymal transec-tion is the potential for bile leaks. However, in a large series of 101 consecutive right hemihepatectomies performed using the stapling technique, there was only one reported bile leak (1%), which sealed after ERCP.168Steps in Commonly Performed Hepatic ResectionsA fundamental understanding of hepatic anatomy is vital for any surgeon with the desire to perform hepatobiliary surgery. Each hepatic resection surgery can be broken down into a series of orderly steps. The key to being a proficient hepatic surgeon is not to operate swiftly but rather to accomplish the operation by completing the steps in an orchestrated fashion. Mastery of the operative steps coupled with knowledge of liver anatomy and the common anatomic variants provides the foundation for safe hepatic


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Surgery_Schwartz. by completing the steps in an orchestrated fashion. Mastery of the operative steps coupled with knowledge of liver anatomy and the common anatomic variants provides the foundation for safe hepatic surgery. There are many different techniques and sequences for accomplishing each of the anatomic (and nonana-tomic) hepatic operations. The authors present their preferred approach in a stepwise fashion for right hepatic lobectomy (right hemihepatectomy), left hepatic lobectomy (left hemihepa-tectomy), and left lateral segmentectomy (left lateral sectionec-tomy). Provision of a detailed approach for every type of liver resection is beyond the scope of this chapter, and readers are referred to several excellent descriptions.169Steps Common to All Open Major Hepatic Resections 1. Make the skin incision—right subcostal with or without a partial or complete left subcostal extension across the mid-line, depending on the patient’s habitus and liver/tumor anatomy.2. Open and explore the abdomen,


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Surgery_Schwartz. subcostal with or without a partial or complete left subcostal extension across the mid-line, depending on the patient’s habitus and liver/tumor anatomy.2. Open and explore the abdomen, and place a fixed table retractor (e.g., Thompson or Bookwalter).3. Examine the liver with bimanual palpation. Perform liver ultrasound, and confirm the operation to be performed.4. Take down the round and falciform ligaments, and expose the anterior surface of the hepatic veins.5. For a left hepatectomy, divide the left triangular ligament; for a right hepatectomy, mobilize the right lobe from the right coronary and triangular ligaments.6. Open the gastrohepatic ligament, palpate the porta hepatis, and assess for accessory or replaced hepatic arteries.7. Perform a cholecystectomy; leave the gallbladder with the cystic duct intact if the gallbladder is involved by the tumor.Right Hepatic Lobectomy (Right Hepatectomy or Hemihepatectomy) 8. Mobilize the liver from the anterior aspect of the IVC in


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Surgery_Schwartz. with the cystic duct intact if the gallbladder is involved by the tumor.Right Hepatic Lobectomy (Right Hepatectomy or Hemihepatectomy) 8. Mobilize the liver from the anterior aspect of the IVC in “piggyback” fashion; ligate the short hepatic veins up to the right hepatic vein (RHV).9. Perform a right hilar dissection—gently lower the hilar plate, then doubly ligate and divide the right hepatic artery (RHA), superior to the right side of the common bile duct.10. Doubly ligate and divide a replaced or accessory RHA if present.11. Expose the portal vein, identifying its right and left branches. There is a small lateral portal vein branch off the right portal vein (RPV) to the caudate lobe that should be controlled and ligated to allow the exposure of additional length on the RPV. Divide the RPV either with a vascular stapler or between vascular clamps.12. Dissect the avascular tissue along the suprahepatic vena cava between the right and middle hepatic veins. Pass a silastic tube of a


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Surgery_Schwartz. RPV either with a vascular stapler or between vascular clamps.12. Dissect the avascular tissue along the suprahepatic vena cava between the right and middle hepatic veins. Pass a silastic tube of a Jackson-Pratt drain through this gap.13. Notch or divide the caudate process crossing to the right hepatic lobe, and bring the drain up and through this notch.14. Hang the liver over the drain by pulling up as you divide through the liver parenchyma.15. Repeat ultrasound and confirm the transection plane, staying just to the right of the middle hepatic vein (MHV) unless the tumor extends over it.16. Cauterize approximately 1 cm into the liver parenchyma, then switch to a hydro-jet dissection device in combination with Bovie electrocautery and suture ligation.17. Continue parenchymal division until the RHV is encoun-tered. During this division, identification, control, ligation, and transection of the right hepatic duct (RHD) are obtained late in the parenchymal transection


Surgery_Schwartz

Surgery_Schwartz. division until the RHV is encoun-tered. During this division, identification, control, ligation, and transection of the right hepatic duct (RHD) are obtained late in the parenchymal transection process.18. Divide the RHV between vascular clamps and suture ligate the RHV.19. Examine the transected liver edge for bleeding; place a figure-of-eight ligating vascular suture if bleeding is encountered.20. Ensure hemostasis of the transected liver edge with an argon beam coagulator and suture ligation.21. Inspect the transection surface for bile leaks. These should be clipped or suture ligated. Applying a dilute solution of hydro-gen peroxide can facilitate the visualization of bile leaks.22. Inspect the IVC and right retroperitoneal space for hemostasis.23. Perform completion ultrasound to confirm left portal vein (LPV) inflow and outflow in the remaining hepatic veins.24. Fix the proximal falciform ligament back to the diaphragm side with figure-of-eight sutures.25. Apply tissue sealant to


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Surgery_Schwartz. left portal vein (LPV) inflow and outflow in the remaining hepatic veins.24. Fix the proximal falciform ligament back to the diaphragm side with figure-of-eight sutures.25. Apply tissue sealant to the cut surface of the liver, and place a Jackson-Pratt drain in the right subphrenic space and close the abdomen (Fig. 31-22).Comments Although some liver surgeons advocate a one-step division of the entire intrahepatic Glissonian pedicle as described by Launois and Jamieson,170 it is the authors’ prefer-ence to divide the RHA, RHD, and RPV in an extrahepatic fash-ion. As for the transection plane, the key is to perform accurate ultrasound visualization and mapping of the MHV and to stay just to the right of it. Weaving in and out or bisecting the MHV can leading to torrential back bleeding. Also, for bulky right lobe tumors adherent to the diaphragm or retroperitoneum, an anterior approach with division of the parenchyma can be per-formed before right lobe mobilization.152,153Left Hepatic


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Surgery_Schwartz. for bulky right lobe tumors adherent to the diaphragm or retroperitoneum, an anterior approach with division of the parenchyma can be per-formed before right lobe mobilization.152,153Left Hepatic Lobectomy (Left Hepatectomy or Hemihepatectomy) 8. Widely open the gastrohepatic ligament flush with the undersurface of the left lateral section and the caudate lobe. 9. Doubly ligate and divide a replaced or accessory left hepatic artery (LHA) if present.Brunicardi_Ch31_p1345-p1392.indd 138320/02/19 2:36 PM 1384SPECIFIC CONSIDERATIONSPART II10. Clamp the round ligament (ligament teres) and pull it ante-riorly as a handle to expose the left hilum.11. Divide any existing parenchymal bridge between segments III and IVB.12. Dissect the left hilum at the base of the umbilical fissure and lower the hilar plate anterior to the left portal pedicle.13. Incise the peritoneum overlying the hilum from the left side, and doubly ligate the LHA (after test clamping and confirming a palpable pulse in


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Surgery_Schwartz. the hilar plate anterior to the left portal pedicle.13. Incise the peritoneum overlying the hilum from the left side, and doubly ligate the LHA (after test clamping and confirming a palpable pulse in the RHA).14. Dissect the portal vein at the base of the umbilical fissure (it will take a nearly 90° bend from the transverse to the umbilical portion).15. Expose the portal vein, identifying the right and left branches. Control the small portal vein branch off the LPV to the caudate lobe to allow the exposure of additional length. Divide the LPV either with a vascular stapler or between vascular clamps.16. Ligate and divide the ligamentum venosum caudally.17. Identify the long extrahepatic course of the left hepatic duct (LHD) behind the portal vein. Ligate and divide the LHD at the umbilical fissure.18. Fold the left lateral segment up and back to the right, expos-ing the window at the base of the left hepatic vein (LHV) as it enters the IVC. This is facilitated by dividing any loose


Surgery_Schwartz

Surgery_Schwartz. fissure.18. Fold the left lateral segment up and back to the right, expos-ing the window at the base of the left hepatic vein (LHV) as it enters the IVC. This is facilitated by dividing any loose areolar tissue overlying the ligamentum venosum, which is divided proximally.19. Pass a large, blunt right-angle clamp in the window between the RHV and the MHV, and hug the back of the MHV, aim-ing for the deep edge of the LHV. Do not force it or perfo-rate the IVC or MHV.20. Pass the silastic tube of a Jackson-Pratt drain through this window.21. Notch or divide the caudate process crossing to the left hepatic lobe and bring the drain up and through this notch.22. Hang the liver over the drain by pulling up as you divide through the liver parenchyma.23. Repeat ultrasound and confirm the transection plane on the anterior surface, staying close to the demarcated line. Do not bisect the MHV as it passes tangentially from the left to the right lobe.24. Cauterize down approximately 1 cm in the


Surgery_Schwartz

Surgery_Schwartz. plane on the anterior surface, staying close to the demarcated line. Do not bisect the MHV as it passes tangentially from the left to the right lobe.24. Cauterize down approximately 1 cm in the liver paren-chyma, then switch to a hydro-jet dissection device in com-bination with Bovie electrocautery and suture ligation.25. Continue parenchymal division until the left/middle hepatic veins are encountered.26. Divide the LHV and MHV between vascular clamps and suture the ligate the LHV/MHV.27. Check the transected edge of the liver for surgical bleed-ing; ensure hemostasis of the transected edge with an argon beam coagulator and suture ligation.28. Inspect the transection surface for bile leaks. These should be clipped or suture ligated. Apply dilute solution of hydro-gen peroxide to facilitate the visualization of bile leaks.29. Perform completion ultrasound to confirm RPV inflow and RHV outflow.30. Apply tissue sealant to the transected surface of the liver. Place a Jackson-Pratt drain


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Surgery_Schwartz. the visualization of bile leaks.29. Perform completion ultrasound to confirm RPV inflow and RHV outflow.30. Apply tissue sealant to the transected surface of the liver. Place a Jackson-Pratt drain in the left subphrenic space and close the abdomen (Fig. 31-23).Comments Because the right posterior duct arises from the left hepatic duct (LHD) in approximately 20% of cases (see Fig. 31-9) and the right anterior duct comes off the LHD in approximately 5% of cases,6 it is vital to divide the LHD at the base of the umbilical fissure and not more centrally in the hilum as it bifurcates. If the LHD were divided as it appears to bifurcate from the right hepatic duct, then approximately 20% to Figure 31-22. Completed right hepatic lobectomy (right hepa-tectomy) with the right portal vein, right hepatic artery, and right bile duct ligated and divided. The right hepatic vein is ligated and divided. Middle hepatic vein branches inside the liver are divided.Figure 31-23. Completed left hepatic


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Surgery_Schwartz. hepatic artery, and right bile duct ligated and divided. The right hepatic vein is ligated and divided. Middle hepatic vein branches inside the liver are divided.Figure 31-23. Completed left hepatic lobectomy (left hepatec-tomy) resecting segments II, III, and IV.Brunicardi_Ch31_p1345-p1392.indd 138420/02/19 2:37 PM 1385LIVERCHAPTER 3125% of the time, either the right posterior or right anterior duct would be transected. After the LHD is divided as described ear-lier (Step 17), the liver parenchyma is scored and divided hori-zontally approximately 1 cm above the left hilum; the surgeon thus assumes that an aberrant right anterior or posterior duct is coming off the LHD in the hilum and preserves it. Then as the parenchymal transection reaches the left side of the gallblad-der fossa, the transection plane turns vertical to run parallel to Cantlie’s line (or the left edge of the gallbladder bed). The left lobe of the liver will be well demarcated at this point (after the vascular


Surgery_Schwartz

Surgery_Schwartz. the transection plane turns vertical to run parallel to Cantlie’s line (or the left edge of the gallbladder bed). The left lobe of the liver will be well demarcated at this point (after the vascular inflow has been divided), which guides the transection plane on the anterior surface. In general, the transection plane should be close to the demarcation line to minimize the amount of devascularized liver remaining. When dividing the LHV and MHV, the surgeon should keep in mind that they have a com-mon trunk approximately 90% of the time. If it is not easy to open the window deep to the MHV and LHV, then division of the MHV and LHV can be accomplished after the parenchymal transection.Left Lateral Segmentectomy (Left Lateral Sectionectomy) 8. Widely open the gastrohepatic ligament flush with the undersurface of the left lateral section and the caudate lobe. 9. Doubly ligate and divide a replaced or accessory LHA if present.10. Clamp the round ligament and pull it anteriorly as a handle


Surgery_Schwartz

Surgery_Schwartz. the undersurface of the left lateral section and the caudate lobe. 9. Doubly ligate and divide a replaced or accessory LHA if present.10. Clamp the round ligament and pull it anteriorly as a handle to expose the left hilum.11. Divide any existing parenchymal bridge between segments III and IVB.12. Carry the dissection down from the end of the round liga-ment, and the segment III pedicle will be encountered.13. Incise the peritoneal reflection on the left side of the round ligament as it inserts into the umbilical fissure. This will facilitate encircling the segment III and II pedicles, which can be divided separately. When encircling the segment II pedicle, take care to avoid injury to the caudate inflow ves-sels coming off the LPV.14. Divide the liver parenchyma, staying flush on the left side of the falciform ligament using Bovie electrocautery.15. Divide the LHV as the parenchymal transection is complete.16. A Pringle maneuver usually is not required for a left lateral


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Surgery_Schwartz. on the left side of the falciform ligament using Bovie electrocautery.15. Divide the LHV as the parenchymal transection is complete.16. A Pringle maneuver usually is not required for a left lateral sectionectomy because complete devascularization occurs before transection and little back bleeding is encountered.Comments If the segment III and II LHA branches are large, they can be individually ligated in the left hilum before the pedicles (with portal vein and hepatic duct branches) are taken. If the tumor is more peripheral in the left lateral segment, then the segment III and II pedicles can be divided with a vascular stapler inside the liver during the parenchymal transection.Pringle and Ischemic PreconditioningPringle described clamping of the portal triad a century ago in the landmark paper “Notes on the Arrest of Hepatic Hemorrhage Due to Trauma.”4 Although the Pringle maneuver was initially described for controlling bleeding due to traumatic liver injury, it is commonly used


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Surgery_Schwartz. paper “Notes on the Arrest of Hepatic Hemorrhage Due to Trauma.”4 Although the Pringle maneuver was initially described for controlling bleeding due to traumatic liver injury, it is commonly used during elective hepatic resections.173,174 The goal is to minimize blood loss and hypotension, which add sig-nificant morbidity to the operation. Furthermore, intraoperative blood transfusion has been shown to be an independent risk fac-tor for increased postoperative infection as well as worse patient survival in some studies. Therefore, all efforts should be made to minimize blood loss during hepatic resection.Although the liver has been shown to tolerate up to 1 hour of warm ischemia, some technical variations of the Pringle maneuver include intermittent vascular occlusion with cycles of approximately 15 minutes on and 5 minutes off. Experimental and clinical studies have demonstrated the efficacy of intermit-tent vascular occlusion in decreasing ischemia/reperfusion injury compared with


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Surgery_Schwartz. 15 minutes on and 5 minutes off. Experimental and clinical studies have demonstrated the efficacy of intermit-tent vascular occlusion in decreasing ischemia/reperfusion injury compared with continuous vascular occlusion, with less eleva-tion of postoperative liver enzyme levels.175 Another variation is selective hemihepatic vascular occlusion, which can reduce the severity of visceral congestion and total liver ischemia. In one prospective trial of total versus selective portal triad clamping, both techniques of inflow clamping were found to be equally effective for patients with normal livers, but greater liver dam-age was observed with total inflow occlusion in patients with cirrhotic livers.176In an attempt to decrease the ischemic damage associated with inflow occlusion, some hepatic surgeons have advocated the use of ischemic preconditioning.177 Ischemic precondition-ing refers to the brief interruption of blood flow to an organ, fol-lowed by a short reperfusion period, and then


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Surgery_Schwartz. surgeons have advocated the use of ischemic preconditioning.177 Ischemic precondition-ing refers to the brief interruption of blood flow to an organ, fol-lowed by a short reperfusion period, and then a more prolonged period of ischemia. In a randomized clinical trial involving 100 patients undergoing major hepatic resection, Clavien and col-leagues reported significantly less liver injury in the group who received ischemic preconditioning with a 10-minute clamp, a 10-minute reperfusion, and then a 30-minute clamp than in those who received a 30-minute clamp alone.178 Patients with steatosis also were especially protected by ischemic preconditioning, and the mechanism was shown to be related in part to preservation of the adenosine triphosphate content of liver tissue.Preoperative Portal Vein EmbolizationThe observation that tumor thrombosis of a major portal vein branch induced ipsilateral lobar atrophy and contralateral lobe hypertrophy led to the concept of intentional preoperative


Surgery_Schwartz

Surgery_Schwartz. EmbolizationThe observation that tumor thrombosis of a major portal vein branch induced ipsilateral lobar atrophy and contralateral lobe hypertrophy led to the concept of intentional preoperative portal vein embolization (PVE) to induce compensatory hypertrophy of the remnant liver. This procedure was first described in the 1980s and is accomplished via a percutaneous, transhepatic route.160,161 Numerous studies have subsequently confirmed that PVE is effective in inducing hypertrophy of nonembolized hepatic segments.86,181 PVE usually is performed in the setting of a planned right trisectionectomy or extended left hepatec-tomy (also referred to as a left trisectionectomy; resection of Couinaud’s segments II, III, IV, V, and VIII of the liver) or extended hepatic lobectomy when it is thought that the patient’s remnant liver will be too small to support liver function. The future liver remnant volume (e.g., the volume of segments II, III, and I) in a patient undergoing a planned right


Surgery_Schwartz

Surgery_Schwartz. that the patient’s remnant liver will be too small to support liver function. The future liver remnant volume (e.g., the volume of segments II, III, and I) in a patient undergoing a planned right trisectionec-tomy can be directly measured by helical CT and then divided by the total estimated liver volume to calculate the percentage of the future liver remnant. If the future liver remnant is thought to be too small, then PVE should be considered to increase the size of the future liver remnant.182 In general, surgery is planned approximately 4 weeks after PVE to allow adequate time for hypertrophy.There is no universal agreement on what constitutes a future liver remnant adequate to avoid postoperative liver fail-ure. It is thought that 25% to 30% of the total liver volume is ade-quate in patients with a normal liver.183 Vauthey and associates reported that major postoperative complications were increased when the estimated future liver remnant was <25%.184 Farges and colleagues


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Surgery_Schwartz. in patients with a normal liver.183 Vauthey and associates reported that major postoperative complications were increased when the estimated future liver remnant was <25%.184 Farges and colleagues conducted a prospective study to assess the benefits of PVE before right hepatectomy. They demonstrated Brunicardi_Ch31_p1345-p1392.indd 138520/02/19 2:37 PM 1386SPECIFIC CONSIDERATIONSPART IIthat PVE had no beneficial effect on the postoperative course in patients with normal livers but significantly reduced postop-erative complications in patients with chronic liver diseases.185 A larger remnant may be necessary even in patients with nor-mal livers when a complex hepatectomy is planned or when the background liver is steatotic.186 This is especially relevant with the increased incidence of fatty liver disease. A larger remnant may also be needed when patients have received pre-operative chemotherapy. Some have suggested that 40% of the total hepatic volume should remain to minimize


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Surgery_Schwartz. of fatty liver disease. A larger remnant may also be needed when patients have received pre-operative chemotherapy. Some have suggested that 40% of the total hepatic volume should remain to minimize postoperative complications in patients who have underlying liver disease or who have received preoperative chemotherapy for colorectal cancer metastases.187,188 In a recent study encompassing 112 patients who underwent PVE, major complications, hepatic insufficiency, length of hospital stay, and 90-day mortality rate were significantly greater in patients with a standardized future liver remnant of ≤20% or a degree of hypertrophy of <5% than in patients with higher values.189 In another study, the authors performed PVE during neoadjuvant chemotherapy for colorec-tal cancer metastases. After a median wait of 30 days after PVE, patients receiving neoadjuvant chemotherapy showed median liver growth of 22% in the contralateral (nonembolized) lobe compared with 26% for those not receiving


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Surgery_Schwartz. a median wait of 30 days after PVE, patients receiving neoadjuvant chemotherapy showed median liver growth of 22% in the contralateral (nonembolized) lobe compared with 26% for those not receiving chemotherapy (not a statistically significant difference), which indicated that liver growth occurs after PVE even when cytotoxic chemotherapy is administered.190 PVE-related complications occur at a relatively low rate and include bleeding, hemobilia, liver abscess, incom-plete embolization, and small bowel obstruction. To augment the ability to increase liver function reserve in patients who have undergone PVE, some groups have added ipsilateral hepatic artery embolization and ipsilateral hepatic vein embolization.191Staged Hepatectomy, ALPPS, and Repeat Hepatic Resection for Recurrent Liver CancerA two-stage hepatectomy is a sequential resection strategy to remove all metastatic liver tumors when it is impossible to resect all disease in a single operative procedure. The first-stage


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Surgery_Schwartz. CancerA two-stage hepatectomy is a sequential resection strategy to remove all metastatic liver tumors when it is impossible to resect all disease in a single operative procedure. The first-stage hepatectomy usually consists of clearance of the left hemiliver by nonanatomic resection, followed by right portal vein ligation or embolization to induce left lobe hypertrophy.192,193 This is fol-lowed by a second-stage major right hepatectomy or extended right hepatectomy to resect the right liver metastases. This approach is most commonly used in cases of initially unresect-able colorectal hepatic metastases and has yielded very good results.193Another technique to increase future liver remnant to avoid post-hepatectomy liver failure is known as “Associating Liver Partition and Portal Vein Ligation for Staged Hepatec-tomy (ALPPS)” and was described in 2012. This technique consists of operative portal vein ligation with in situ liver tran-section along the future line of resection leaving


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Surgery_Schwartz. for Staged Hepatec-tomy (ALPPS)” and was described in 2012. This technique consists of operative portal vein ligation with in situ liver tran-section along the future line of resection leaving the arterial and hepatic vein branches intact.194 There have been several techni-cal modifications to the original description, and this remains a hot topic that is actively debated (ALPPS vs. PVE) at the current liver surgery meetings.The majority of patients undergoing hepatic resection for colorectal cancer metastases experience a recurrence. For those with limited disease recurrence confined to the liver, repeat hepatectomy is a reasonable option and can be performed with low morbidity and mortality in experienced hands.195 In one study, 126 patients who underwent a second liver resection for colorectal cancer metastases had 1-, 3-, and 5-year survival rates of 86%, 51%, and 34%, respectively. By multivariate analysis, the presence of more than one lesion and a tumor size of >5 cm were


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Surgery_Schwartz. colorectal cancer metastases had 1-, 3-, and 5-year survival rates of 86%, 51%, and 34%, respectively. By multivariate analysis, the presence of more than one lesion and a tumor size of >5 cm were independent prognostic indicators of reduced survival.196 In another study, 40 patients underwent a second hepatectomy for liver metastases from colorectal cancer and experienced a survival benefit similar to that from the first hepatectomy; how-ever, the results suggested that this approach should be limited to those patients who do not have extrahepatic disease and for whom >1 year has elapsed since the first operation.197 A meta-analysis of 21 studies examining clinical outcomes after first and second liver resections for colorectal cancer metastases showed that repeat hepatectomy was safe and provided a sur-vival benefit equal to that from the first liver resection.198Repeat hepatectomy also has been performed in patients with HCC. Nakajima and colleagues reported on follow-up of 94


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Surgery_Schwartz. and provided a sur-vival benefit equal to that from the first liver resection.198Repeat hepatectomy also has been performed in patients with HCC. Nakajima and colleagues reported on follow-up of 94 patients who underwent curative liver resection for HCC from 1991 to 1996.199 Of these, 57 patients had isolated recur-rent disease in the liver. Twelve of these 57 patients underwent repeat hepatic resection, whereas the other 45 patients received ablation therapy. The overall survival rate in those undergoing a second hepatectomy was 90% at 2 years; however, the disease-free survival rate was only 31% at 2 years, significantly lower than the 62% rate after initial hepatectomy. Likewise, in another group of 84 patients who underwent second hepatectomy for recurrent HCC, the overall 5-year survival rate was 50%, but the recurrence-free survival rate was only 10%.200 In a report of 67 patients undergoing a second resection for HCC, over-all 1-, 3-, and 5-year survival rates were 93%, 70%,