Chapter 17 Laparoscopic Liver Resection

Robert C.G. Martin, II., Charles R. ST. Hill, Russell E. Brown

The videos associated with this chapter are listed in the Video Contents and can be found on the accompanying DVDs and on Expertconsult.com.

Hepatic resection for metastatic disease has been practiced for decades. Lortat-Jacob described right hepatectomy for secondary malignancy in 1952. Initial anecdotal success has been followed by continued improvements in survival. The progressive success of colorectal liver metastasis resection can be attributed to improvements in multimodality therapy, including systemic chemotherapy and targeted therapies, as well as efforts to increase the proportion of patients eligible for resection. Additional improvements in surgical and anesthetic techniques, as well as postoperative care, have made hepatic surgeries safe at specialized centers.

Laparoscopic liver resections have been reported since 1992, with formal anatomic resections described in 1996. In contrast to many intra-abdominal procedures, the laparoscopic approach to hepatic resection has been adopted more cautiously. This is largely a result of concerns regarding difficulty in liver mobilization, parenchymal transaction, the perceived risks for hemorrhage, and the size of the specimen to be exteriorized. Carbon dioxide gas embolism, tumor dissemination, and inferior oncologic results were also among early fears. However, hepatobiliary units are increasingly reporting success with this approach. Their patients have benefited from a reduction in blood loss, reduced postoperative morbidities, and shorter hospital stay with equivalent rates of negative margins. Careful analysis of outcomes and establishment of training paradigms are necessary to benefit the population at large. With this, there is expected growth in the use of laparoscopic liver resection for benign, malignant, and transplantation applications.

This chapter focuses on laparoscopic liver resection from the perspective of metastatic disease because this is the most common indication for the general surgeon. The principles discussed can be applied to resection for other causes. The laparoscopic technique for right hepatectomy is described in detail in this chapter; the same principles, however, apply to other anatomic resections.

Operative indications

The Louisville Statement, based on an international consensus meeting, concluded that laparoscopic liver resection is well accepted for solitary lesions measuring 5 cm or less that are located in segments 2 to 6. Multiple lesions, larger lesions, and those in the more challenging segments 1, 7, and 8 may also be resected; however, this should be limited to specialized centers and surgeons with significant experience in this field.

In considering the types of lesions amenable to resection, there are many, including benign and malignant neoplasms. Hepatic adenomas, when large, symptomatic, or with concerning features on imaging studies, can be resected using laparoscopic techniques. Adenomas larger than 4 cm may have increased risk for hemorrhage and are appropriate for resection. If the tumor is smaller than 4 cm but causing significant symptoms, it can also be resected. Because of the low malignant potential of a small symptomatic lesion, ablation techniques should also be considered in their management.

Several series have reported results equivalent to open resection for both hepatocellular carcinoma and colorectal liver metastasis. Hepatic resection, when feasible, is the only treatment associated with long-term survival. Based on a review of actual 10-year survivors who underwent resection before 1994 (i.e., before the use of “modern” chemotherapy), we can postulate current 10-year survival in at least one out of six patients after resection of colorectal liver metastasis.

Laparoscopic live-donor hepatectomy is becoming more prevalent but remains controversial. This should be performed only by experienced surgeons and under the auspices of a worldwide registry.

Alternative therapies

One of the most widely accepted nonresection techniques for addressing hepatic tumors is local tumor ablation. The rationale underlying the use of local ablative therapies for metastatic colorectal cancer rests largely on the observed survival benefit after resection of colorectal liver metastasis, and three theoretical concepts: (1) tumor consolidation, (2) oligometastases, and (3) the Norton-Simon hypothesis. After highly effective systemic therapy, micrometastases are eradicated, leaving behind stable macrometastatic tumor burden. This concept, known as tumor consolidation, leads to the thought that elimination of this “consolidated” tumor may yield a survival benefit. The oligometastases theory assumes that a subgroup of patients are identified to have a focal area of metastatic disease that is not yet widely disseminated. This subgroup may benefit from complete ablation of this metastatic focus. Finally, the Norton-Simon hypothesis states that effectiveness of chemotherapeutics is proportional to tumor growth rate. Decreasing the overall tumor burden by “debulking” will result in a smaller volume of more rapidly dividing metastatic cells that are more chemosensitive.

Nonresectional liver-directed therapies can be broadly categorized as catheter based (e.g. transarterial chemoembolization, drug-eluting bead therapy, and radioembolization) or intraparenchymal ablative techniques. The two most widely used intraparenchymal ablative modalities for colorectal liver metastasis by surgeons are radiofrequency ablation (RFA) and microwave ablation (MWA). A discussion of cryoablation and of emerging ablative technologies (e.g., laser interstitial thermal therapy, irreversible electroporation, and high-intensity focused ultrasound) is also included.

Hyperthermic Ablative Technologies

Modern hyperthermic ablative technologies rely on exposure of tumors to supranormal temperatures to ablate intrahepatic tumors. This takes advantage of the tumor’s inability to dissipate heat by augmenting blood flow that is found in healthy tissues. In contrast to cryotherapy, which is used for tumors that are more resistant to freezing than normal cells, malignant cells are more sensitive to hyperthermic damage than normal cells.

For most tumors, exposure to temperatures above 42° C results in low-level thermal injury, with more effectiveness noted with increased exposure time and temperature. At progressively higher temperatures, there is an exponential and inverse relationship between treatment temperature and the exposure time needed to achieve cell death; thus, higher treatment temperatures require less exposure time for successful ablation. Temperatures above 60° C lead to cell death through complex interactions involving apoptosis, microvascular damage, ischemia-reperfusion injury, Kupffer cell activation, altered cytokine expression, alterations in the immune response, RNA and DNA destruction, dissolution of lipid bilayers, and protein denaturation. Thermal coagulation begins in the range of 70° C, and tissue desiccation occurs at about 100° C.

Radiofrequency Ablation

RFA achieves local hyperthermia using high-frequency alternating electric current in the radiofrequency range (100 to 500 kHz). Local hyperthermia results from ionic vibration and frictional heating of surrounding tissues. RFA gained popularity in the 1990s and serves as the prototypical ablation platform for most clinicians today.

Radiofrequency current is applied through an electrode that is deployed within the tumor, using ultrasound, computed tomography (CT), or magnetic resonance imaging (MRI) guidance. RFA probes were initially developed as single-needle electrodes but have evolved to multiprobe and internally cooled arrays with attendant increases in treatment volumes and more reliable geometric ablation zones. Several devices are marketed worldwide, and none has emerged as superior with regard to ablation size, reproducibility, or local tumor control.

Percutaneous, laparoscopic, and open surgical approaches have been successfully used for RFA treatment, each with inherent advantages and disadvantages. The choice of approach should be individualized based on tumor anatomy, extent of disease, and patient comorbidities. An open surgical approach to RFA is preferable for patients with large tumors, multiple tumors, and tumors near large blood vessels that may otherwise be inadequately ablated because of heat-sink effects. Hepatic inflow occlusion (Pringle maneuver) diminishes the heat-sink effect from large intrahepatic vessels and is easier with open surgery compared with laparoscopic surgery. An open approach also allows for extremely accurate intraoperative ultrasound, which facilitates ablation of large tumors near blood vessels or in difficult anatomic regions of the liver. Peripherally situated tumors may be safely ablated by packing adjacent organs away from the liver, thus providing a layer of protection difficult to achieve with other approaches. Thoracic transdiaphragmatic approach to tumors near the dome of the liver has also been described, and this technique may be useful for patients in whom multiple prior surgical procedures have resulted in prohibitive perihepatic scar tissue.

Laparoscopic RFA is an option for patients with tumors for which percutaneous RFA is not feasible or safe, such as peripherally situated tumors near adjacent organs like the stomach or colon. Patients may benefit from the decreased incisional morbidities and faster recovery times afforded by a laparoscopic approach. However, prudent surgical judgment must be exercised in selecting patients for whom the laparoscopic approach is appropriate, and oncologic principles should not be compromised intraoperatively. Modern endoscopic optics and laparoscopic ultrasound probes permit excellent visualization, making this approach increasingly attractive.

Percutaneous RFA is well suited for patients with colorectal liver metastasis who are not good candidates for more invasive procedures because of comorbid conditions. In general, percutaneous RFA requires tumor sizes and locations that can be accessed without damaging adjacent organs or vascular structures. Although CT-guided RFA is relatively easy for small tumors in the lower segments of the liver, tumors along the periphery of the liver can pose a challenge for safe access. Artificially induced ascites or pleural effusions by injection of dextrose solution has been reported as a means of “separating” vulnerable nearby organs, thus potentially expanding the application of this modality. Cirrhotic patients and those with limited intrahepatic recurrences after hepatectomy are examples of patients who may be best served by a percutaneous approach.

Regardless of the device or approach used, attention to RFA probe placement is critical to successful tumor ablation. Careful assessment of preablation imaging studies (CT or MRI) and thorough ultrasound examination of both the tumor and surrounding hepatic anatomy during treatment assist with successful probe placement. Ultrasonography can monitor the progression of the ablation during RFA. Gas bubbles generated by an ablation may interfere with accurate ultrasonography of tissues deep to the electrode, which can hinder repositioning of the electrode for overlapping ablation zones when treating larger tumors. Initial ablation of the deepest portions of the tumor, followed by serial redeployment as the electrode is withdrawn, may mitigate this effect. Imaging-related difficulties may be more pronounced with the percutaneous approach; however, an immediate post-RFA CT can be readily performed to assist with the assessment of the ablation zone.

Complication rates associated with RFA are low, ranging from 2.4% to 27%, depending on the threshold for defining complications. By compiling more than 1300 patients from 18 different studies, Scaife and Curley reported an overall mortality rate of 0.5%, a major complication rate of 2%, and a minor complication rate of 6% after hepatic RFA. The risk for hepatic failure is quite low following RFA, even in patients with abnormal hepatic parenchyma. For this reason, RFA seems particularly attractive for cirrhotic patients. Monopolar RFA requires careful placement of grounding pads before ablation because inadequate electrical grounding has been implicated in full-thickness skin burns. Other potential complications following RFA include wound infections, intra-abdominal abscess, renal failure, hepatic abscess, biliary tract injury, pleural effusion, fever, pain, and minor hemorrhage. A “postablation syndrome” has also been described and is characterized by low-grade fever, malaise, chills, myalgia, delayed pain, and nausea and vomiting. This syndrome is usually self-limited and resolves within 10 days but must be differentiated from more serious postoperative complications. Both RFA and MWA can be safely performed in patients with implanted cardiac devices but require coordination with cardiologists and perioperative device interrogation.

Because there are no published randomized controlled trials comparing RFA and resection, the effectiveness of RFA in colorectal liver metastasis is largely based on several single-arm, retrospective, or prospective studies. These studies have inherent flaws related to selection bias, differing end points, and varying definitions of eligibility for RFA or resection. However, available data suggest that RFA is an effective treatment modality in improving survival in colorectal liver metastasis. In a clinical evidence review, Wong and associates noted the wide variability in reported 5-year survival rates (14% to 55%) and local recurrence rates (3.6% to 60%) following RFA, which are indicative of variability in selection criteria, treatment experience or technique, and end points across multiple institutions.

Despite the variability in study designs, the preponderance of evidence supports the superiority of resection over RFA and the benefit of RFA over systemic chemotherapy alone. Abdalla and associates compared 368 patients who underwent potentially curative procedures (resection only, resection with RFA, and RFA only) with 70 patients with liver-only disease who received only regional or systemic chemotherapy. Importantly, this series used patients with unresectable disease confirmed at laparotomy as the control group, rather than historical controls. They noted significant differences in both overall recurrence rates of 52% (resection only), compared with 64% (resection + RFA) and 84% (RFA only), and 4-year survival rates of 65%, 36%, and 22% for resection, resection + RFA, and RFA only, respectively.

Abdalla and associates noted a survival advantage for patients undergoing either resection with RFA or RFA alone compared with chemotherapy only (P = .0017). Also, in a series by Berber and colleagues, 135 unresectable patients were treated with laparoscopic RFA. Their median survival of 28.9 months was compared with the historical survival of 11 to 14 months using chemotherapy alone, showing significant improvement with RFA. These data suggest that RFA, although not superior to resection, does expand the armamentarium of surgeons. It allows for treatment options beyond chemotherapy alone for patients not amenable to resection, with the potential for improved survival.

Tumor number has been shown to affect both survival and recurrence rates; patients with solitary colorectal liver metastasis have a better outcome than those with multiple metastases. Tumor size is an important factor affecting the rate of local recurrence following RFA, with multiple groups associating colorectal liver metastasis tumor diameter of 4 cm or greater with increased rates of local recurrence. Whether this is a function of unfavorable tumor biology or a limitation of current ablative technologies is a matter of ongoing debate. The relationship between increasing tumor size (or number) and increasing risk for local recurrence highlights the need for early detection and intervention for low-volume colorectal liver metastasis.

Choice of treatment approach (open, laparoscopic, or percutaneous) may also influence local recurrence risk. Eisele and Kuvshinoff and their colleagues showed lower rates of local recurrence for open and laparoscopic RFA compared with a percutaneous approach. Improvements in hepatic exposure and the increased sensitivity of intraoperative ultrasound allowed by an open or laparoscopic RFA approach likely contribute to the lower local recurrence rates after operative compared with percutaneous RFA. Additionally, open and laparoscopic approaches allow for visual inspection of the liver surface for occult lesions and of the peritoneal cavity for extrahepatic disease. The apparent superiority of operative RFA is most likely due to better visualization, better control of surrounding structures, and more sensitive inspection of the peritoneal cavity.

Microwave Ablation of Colorectal Liver Metastasis

MWA, like RFA, is a hyperthermic ablative modality used in the treatment of colorectal liver metastasis. MWA uses microwave frequencies (≥900 MHz) to stimulate water molecules in target tissues, with resultant heat generation and thermal ablation. Although RFA uses ionic agitation to produce heat, MWA induces rotation of water molecules with resultant rapid increases in temperature. MWA was first developed as a hemostatic adjunct to parenchymal transection during hepatectomy. It gained in popularity (largely in the Eastern hemisphere) for the treatment of hepatocellular carcinoma, and later for liver metastases. Recent approval for MWA devices has led to increased use within the United States.

In clinical practice, MWA is similar to RFA in many respects, namely in selection of candidates, the device safety profile, and the approach to probe placement. Advantages of MWA include speed (median ablation times of 10 minutes), the ability to simultaneously ablate with multiple antennae, and lack of grounding-pad complications. Other advantages have been suggested with regard to larger active (as opposed to conductive) heating zones and avoiding the limitations of increased impedance around RFA probes. Probes for MWA include single- and multiple-antenna arrays as well as loop antennae for expanded ablation zones. As with RFA, MWA can be performed through percutaneous, laparoscopic, or open surgical approaches. The reasons for choosing one approach over another parallel the rationale for RFA discussed previously.

Although data are limited, survival and local recurrence rates after MWA appear to be comparable to those associated with RFA. The authors have reported on 50 patients with unresectable colorectal liver metastasis treated by MWA. At a median follow-up of 3 years, recurrences at the ablation site were noted in 6% of patients, with a median disease-free survival of 12 months and a median overall survival of 36 months. As with RFA, MWA has also been employed in combination with hepatic resection for patients with colorectal liver metastasis not amenable to one-stage resection. Tanaka and coworkers reviewed 53 patients with five or more bilobar metastases who underwent either resection or resection plus MWA. At a median follow-up of 21 months, they noted no significant difference between the two groups with respect to overall, disease-free, or hepatic recurrence-free survival. The 3-year overall survival was similar for patients who required combined resection-ablation and those who underwent hepatectomy alone.

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