Chapter 46A. Perspective on Liver Surgery

Interest and experience with surgical treatment of the liver has expanded dramatically over the past two decades. The size of the pool of surgeons who routinely perform liver-directed surgery has also increased. These changes and expansion have been fueled by improved description, understanding, and study of segmental liver anatomy and the numerous potential variations in hepatic arterial, portal venous, hepatic venous, and bile duct anatomy. A key example is the description of segmental hepatic anatomy by Couinaud with an appreciation of the vascular anatomy and associations with the eight segments of the liver (Fig. 46A-1).

As with many other types of potentially complex surgical procedures, operations on the liver now occur more commonly because of enhanced safety. Procedures and techniques have evolved to minimize blood loss which reduces the morbidity related to transfusion of multiple units of blood. Hepatobiliary surgeons can be as idiosyncratic as any other group of surgical specialists; each individual surgeon has his or her own favorite technique or techniques for hepatic transection. The number of possible techniques to perform liver transection safely has grown based on the interest from medical device manufacturers to produce novel equipment to permit liver parenchymal transection while minimizing blood loss. It is not unusual for there to be an array of equipment in the operating room of the modern hepatobiliary surgeon with the goal being to perform the operation with maximum safety and improved patient outcome.

The liver is unusual in the human body as it has a dual blood supply, the portal vein and the hepatic artery. It has been known for almost a 100 years that occlusion of the portal vein and hepatic artery during operation on the liver, be it for a traumatic injury to the liver or for elective resection of a portion of the liver, can reduce blood loss. Advances in our understanding using this technique have led to the realization that inflow occlusion of the hepatic blood supply can be performed safely for carefully controlled periods even in patients with cirrhotic livers. Furthermore, intermittent occlusion followed by brief periods of reperfusion of the liver will increase the total time of inflow occlusion that can be achieved while still successfully limiting blood loss and reducing the risk for ischemic liver injury.

Despite an ever expanding selection of antibiotic agents, pyogenic liver abscess is as common a problem today as it was in the preceding century. If anything, treatment of pyogenic liver abscess with antibiotic therapy is more difficult and has been complicated by the indiscriminate use of antibiotics over the past several decades. Iatrogenic etiologies of liver abscess may have also been increased by the more invasive and aggressive approaches to benign and malignant pancreatic and biliary tract diseases. Endoscopic retrograde cholangiopancreatography, placement of internal stents, or percutaneous placement of external stents in patients with biliary obstruction can increase the likelihood of the development of a pyogenic liver abscess. Furthermore, immunocompromised patients, such as those receiving cytotoxic chemotherapy for malignant disease, are at increased risk to develop hepatic abscess. The primary treatment approach continues to be medical antibiotic therapy and percutaneous interventional radiology aspiration or drainage of abscesses when possible. However, there is still an occasional role for surgical drainage of a complex or multiloculated abscess.

Amebic liver abscess is an extremely common problem worldwide. It should not be forgotten in patients treated in the United States because of the number of people who travel to high-risk areas or who have immigrated to the United States from endemic regions. This is particularly true in the southern, southwestern, and western United States. The diagnosis of amebic liver abscess should be entertained in patients with imaging evidence of a hepatic abscess and an appropriate history and risk group. Treatment is generally medical therapy with occasional need for aspiration or percutaneous drainage.

An echinococcal or hydatid cyst of the liver is an extremely common cause of cystic liver disease worldwide. It is critical to consider this in the differential diagnosis of a patient with a liver cyst because aspiration and spillage of the cyst contents can produce an anaphylactic reaction and spread of the scoleces throughout the peritoneal cavity. This diagnosis should be considered in individuals living in high-risk areas of the world, and once again, may arise in immunocompromised individuals. Management of small cysts involves medical therapy with benzimidazoles. However, this is rarely successful alone, and treatment of larger lesions may also require very careful percutaneous aspiration of all cyst contents followed by installation of the cyst cavity with protoscolecidal agents. Surgical treatment still has a primary role in management of hydatid cysts of the liver and may include resection of the area of the liver bearing the cyst or complete drainage of the cyst while preventing spillage of cyst contents.

Simple liver cysts are diagnosed frequently in patients who are undergoing upper abdominal ultrasound or axial body imaging for some other diagnostic purpose. It is particularly common in patients with malignant disease during staging to be referred to a hepatobiliary surgeon with a finding of cystic lesions in the liver. The question arises from many oncologists as to whether or not these are worrisome and a concern for metastatic disease is often raised. Asymptomatic simple cysts essentially are a radiographic finding and do not require any therapeutic intervention. In the unusual case of giant cysts that are causing pain or compression on adjacent structures, either an open or laparoscopic unroofing of the cyst can be performed as long as there is no connection to the biliary tract. A laparoscopic approach is my preferred treatment for patients with symptomatic simple cysts of the liver as the recovery time is rapid and the symptom relief rate without recurrence of symptoms exceeds 95%. If a biliary tract connection is recognized, concern must be raised for a possible biliary cystadenoma or cystadenocarcinoma. Most of the cystic neoplasms are benign, but complete resection of both benign and malignant neoplastic cysts of the liver is mandatory to prevent a local recurrence of disease. Cystadenoma or cystadenocarcinoma should be suggested if aspiration of a cyst reveals either bile-stained or mucinous fluid.

Similar to asymptomatic simple cysts of the liver, patients with solid benign tumors of the liver are often referred to hepatobiliary surgeons after either a transcutaneous ultrasound or an axial body imaging technique reveals a single or multiple solid lesions. Cavernous hemangiomas, hepatocellular adenomas, and focal nodular hyperplasia may be found in almost one in five patients undergoing a liver imaging technique. It is not uncommon for an individual patient to have more than one type of benign hepatic tumor. Like asymptomatic simple cysts, hemangiomas and focal nodular hyperplasia of the liver are usually only radiographic findings and not associated with symptoms. In those unusual situations where these lesions are large or symptomatic, surgical resection with either an open or laparoscopic approach is indicated. Parenthetically, a significant proportion of early laparoscopic resections were performed for benign solid tumors of the liver that may have not required any type of resection. A benign solid or cystic neoplasm of the liver in an area that is technically feasible to resect with a laparoscopic approach is not an indication for a resection if the lesion is asymptomatic. Hepatic adenomas can grow in size over time and have been associated with two potentially catastrophic outcomes, rupture of the lesion with intraperitoneal hemorrhage or transformation into malignant hepatocellular carcinoma (HCC). Taking female patients off oral contraceptives or other forms of estrogen replacement therapy may lead to reduction in the size of hepatic adenomas, but most hepatobiliary surgeons agree that lesions larger than 4–5 cm should be treated with surgical resection.

HCC is one of the most common solid tumors worldwide. There are estimates that anywhere between ½ and 1 million new patients are diagnosed annually worldwide with this particularly lethal malignancy. Most cases of HCC are associated with concomitant liver injury or established cirrhosis. The chronic liver injury can arise from a number of environmental or hereditary causes, but the most common etiologic agents are chronic hepatitis B and/or C infection and alcohol abuse. The presence of cirrhosis may limit the role of the hepatobiliary surgeon even in patients with reasonably early-stage disease. Surgical treatment is still considered the gold standard in therapy for HCC but only a small minority of patients are candidates for surgical treatment approaches. These treatments include orthotopic liver transplantation based on defined patient-inclusion criteria, resection in patients with adequate functional hepatic reserve remaining after an anatomic or nonanatomic liver resection, and thermal ablation techniques in patients with small lesions but cirrhosis too severe to permit resection. As pointed out in the chapter by Cho and Fong, the 5-year survival rates after resection for HCC have ranged from approximately 20 to 75%. In orthotopic liver transplant series that accrued patients after proper patient selection criteria were established the 5-year survival rates vary from 45 to 75%.

Unfortunately, in most large treatment centers that see a large volume of HCC patients, less than 10% are candidates for surgical treatment. The reasons for exclusion from surgical treatment may include presentation with advanced-stage or metastatic disease, major vascular invasion by tumor, paucity of organs for transplantation, and severity of cirrhosis too great to permit surgical treatment. There have been numerous types of regional and systemic therapies used to treat HCC in patients who are not candidates for surgical treatment. This is a highly resistant and aggressive disease and sadly very few patients who are not candidates for surgical treatment survive more than 2 years, much less having a chance at 5-year survival. Worldwide, the overall mortality rate for HCC in all patients exceeds 94%, so it is clear that better screening programs to diagnose patients at an earlier stage of disease would be highly desirable. It is not clear if such screening programs would be cost effective but this will become an issue due to the increased incidence of this disease in both modern and less developed regions of the world. Similarly, programs aimed at prevention of disease are crucial. Hepatitis B vaccinations have made an impact on the incidence of this cancer in portions of the world where chronic hepatitis B infection is hyperendemic. There is no vaccine for hepatitis C and this virus is supplanting hepatitis B virus as the most common cause of HCC worldwide. Education and prevention are important factors, but clearly better treatments are also needed for this lethal disease. Currently the oral agent sorafenib, a multiple tyrosine kinase inhibitor, has become a standard therapy for patients with advanced and unresectable HCC. However, use of sorafenib enhances survival by an average of less than 3 months, so more effective therapeutic agents for patients with advanced disease must be sought and developed.

Cholangiocarcinomas may arise from the extrahepatic bile ducts, the intrahepatic bile ducts, or the gallbladder. As with HCC, complete surgical resection of cholangiocarcinoma offers the patient the best opportunity for long-term survival. For extrahepatic bile duct cancer and gallbladder cancer, identifying the association of tumors in the bile ducts with key vascular, lymphatic, and hepatic structures is critical to optimize the resection. An excellent example is the importance of caudate resection in patients with hilar cholangiocarcinoma as direct extension of these cancers along small bile ducts directly into the caudate is a common site of failure in patients undergoing a resection that does not include the caudate. Resection of regional lymph nodes is recommended in patients with gallbladder cancer and cholangiocarcinoma and is important for staging. It is not clear that adjuvant therapy significantly improves the long-term outcome of patients but some small studies of systemic chemotherapy or chemoradiation therapy have suggested improved local disease control and possibly an improved median disease-free survival time. Cholangiocarcinomas generally arise in patients with no evidence of cirrhosis or concomitant risk factors for the development of chronic liver injury so major liver resection can be performed more frequently in this patient population. Discussion in the surgical literature has ranged widely regarding the volume of liver that must be resected as part of an operation for cholangiocarcinoma, particularly for gallbladder cancer or hilar cholangiocarcinoma. My general philosophy and data from our experience indicates that major extended hepatectomy should only be performed if this is the procedure that is required to permit complete resection of the tumor with negative resection margins. As previously noted, resection of the caudate is important as a component of the resection of patients with hilar cholangiocarcinoma, but the volume of other liver that must be resected should be based on leaving as much normal, non-malignant liver as possible after the resection.

HCC is the most common reason for hepatic resection or surgical treatment of malignant liver tumors in parts of the world where chronic hepatitis B and C virus infections are common. In most western countries, surgical resection of colorectal cancer liver metastases is a primary focus of many hepatobiliary surgeons. Following the report in the late 1980s of a retrospective analysis of tumor registry data, it was recognized that patients undergoing hepatic resection of colorectal metastases can achieve long-term disease-free and overall survival. While there has not been, and likely never will be a randomized prospective controlled clinical trial comparing resection of colorectal cancer liver metastases with nonsurgical treatment, it is accepted by both the surgical and medical oncology communities that properly selected patients should be considered for surgical treatment of their colorectal cancer liver metastases. Like cholangiocarcinoma, most patients with colorectal cancer liver metastases have relatively normal liver function. This being said, it has been recognized in the last decade that patients with steatohepatitis, caused either by obesity and dietary excesses or iatrogenically by the extensive and prolonged use of neoadjuvant chemotherapy that causes hepatic inflammation, can increase the risk of complications and even mortality related to liver failure after major hepatic resection. Many hepatobiliary surgeons prefer to proceed directly with resection of colorectal cancer liver metastases if the patient has technically resectable disease and an adequate functional hepatic volume remaining after the operation. Others advocate for the use of short courses of neoadjuvant therapy to assess the biological response in the tumors to potentially effective systemic agents. Ultimately, hepatobiliary surgeons will operate on some colorectal cancer patients who have received extensive systemic therapy. It has now been recognized that patients who initially present with clearly unresectable disease but who have a dramatic response to systemic therapy may be considered candidates for resection and can achieve 5-year survival rates in excess of 35% following operation. Ongoing clinical trials internationally will be important to understand the role of neoadjuvant and adjuvant therapy after surgical resection of colorectal cancer liver metastases. Surgeons and patients should be encouraged to enter these trials to provide much needed information on optimal multidisciplinary treatment of stage IV colorectal cancer.

The early retrospective studies indicated that approximately one-third of patients treated with surgical resection achieved a 5-year overall survival. Improved patient selection, routine use of intraoperative ultrasonography to detect small lesions not found on preoperative imaging studies, and improved surgical techniques have produced 5-year survival rates of almost 60% in more recent studies. Additionally, we now know that even a small tumor-free resection margin can be associated with improved patient outcomes, so aggressive surgical approaches should be considered even in tumor that is near major central portal or hepatic venous structures. The routine but selective use of preoperative portal vein embolization (PVE) to induce compensatory hypertrophy in the future liver remnant has also improved the ability to perform major extended hepatectomies safely. The compensatory hypertrophy that occurs after PVE is rapid and most patients can undergo an operation 4–6 weeks after PVE. We, and other surgical groups, have also been aggressive about applying staged hepatic resections in properly selected patients. Performing a two-stage liver resection with or without PVE is associated with long-term survival in over one-third of the treated patients. It is important to recognize that discussing such an aggressive surgical approach is considered reasonable and rational because the 5-year survival rate in patients with unresectable colorectal cancer liver metastases treated with active chemotherapeutic drugs continues to be 5% or less. Furthermore, the surgical mortality rate in high volume centers is less than 3%.

As noted previously, intraoperative ultrasonography is critical for the hepatobiliary surgery performing resection for colorectal cancer, or for other solid tumor liver metastases. Despite improvements in axial body imaging, I still find additional small tumors not seen on preoperative imaging studies in up to 10% of patients undergoing resection. These lesions may be in area of the liver that is planned to be resected or may be on the contralateral side of the liver requiring wedge resection, staged resection, or concomitant thermal ablation of the additional small tumors. I routinely map the location of major intrahepatic portal and hepatic venous structures. This allows the safe application of linear vascular staplers in patients with nonsteatotic or noncirrhotic livers. I also use ultrasonic dissection devices combined with saline-enhanced cautery devices to perform a safe and relatively bloodless liver transection. Inflow occlusion can be applied judiciously, but many patients require no inflow occlusion when using vascular stapling and other liver transection techniques. I am not an advocate for any specific technique as being superior, I am a firm believer that all surgeons should be well versed in use of equipment available for safe hepatic transection and should use techniques with which they are comfortable and confident in their results.

Prior to 2000, there were a paucity of active systemic chemotherapeutic agents in the United States to treat stage IV colorectal cancer. In the 1980s and 1990s, surgical placement of hepatic artery infusion (HAI) pumps was a treatment that was often considered in patients with stage IV colorectal cancer confined to the liver that was not resectable. Unfortunately, regional chemotherapy, while associated with increased rates of measurable partial response, was not associated with an improved long-term survival rate. Additionally, there were toxicities peculiar to HAI chemotherapy, including chemical hepatitis and biliary sclerosis. There have been trials published supporting the use of adjuvant HAI chemotherapy which may reduce the likelihood of recurrence of disease in the liver after liver resection, but this approach has not gained general acceptance. Currently, HAI therapy is performed at few centers in the country and should be considered only as part of a clinical trial.

Tumor ablation techniques continue to evolve. Radiofrequency ablation (RFA) has been applied to treat unresectable HCC as well as unresectable liver metastases from colon and other types of solid malignancies. In my mind it would not be appropriate to consider a trial that would randomize patients with resectable colorectal cancer to resection versus thermal tumor ablation. Well-trained hepatobiliary surgeons can perform resection with low-morbidity and mortality rates and even the most meticulous application of thermal tumor destruction techniques such as RFA, laser tumor ablation, or microwave tumor ablation are associated with incomplete tumor destruction in as few as 5% and as many as 20% of patients. Nonetheless, thermal ablation has permitted treatment of patients with otherwise unresectable disease and we have learned how to apply to it appropriately in patients. The risk of incomplete tumor destruction is much higher in tumors larger than 4 cm in diameter or in lesions that abut major vascular structures. Tumors that are near major hilar structures should not be treated with thermal ablation techniques unless some special circumstance allows installation and infusion of cooled solutions into the biliary system to prevent bile duct injury. This is somewhat extreme and while technically feasible, should not be considered routinely and should be performed only as part of clinical trials in the hands of experienced practitioners. I do commonly perform concomitant RFA of small contralateral tumors in patients undergoing right or left hepatectomy or extended right or left hepatectomy. This must be applied judiciously as a surrounding zone of normal hepatic parenchyma will be destroyed by the ablation technique and consideration must always be given to the amount of liver volume that will remain following a combined resection and ablation procedure.

Surgeons should understand the role and timing of application of surgical treatment for localized hepatic infections. Similarly, patients are often referred after a benign tumor of the liver is encountered during some type of imaging study. These generally do not require surgical treatment but certain lesions, particularly hepatic adenomas, do require close follow-up evaluation and symptomatic or large lesions can be treated by either laparoscopic or open surgical resection. The surgical treatment of primary and metastatic solid tumors that are confined to the liver will continue to have an important role. This remains the gold standard for treatment for these patients and offers the best opportunity for long-term disease-free and overall survival. We must continue to take the lead in investigation of neoadjuvant and adjuvant multidisciplinary approaches in both primary and metastatic hepatic malignancies in an attempt to improve further the outcomes for our patients.