**Abstract**

Hepatocellular carcinoma (HCC) represents the third most common cause of cancer-related death, showing incremental growth rates throughout the last decades. HCC requires multidisciplinary approach in a group of patients suffering from underlying chronic liver disease, usually in the setting of cirrhosis. The mainstay of treatment in resectable cases is surgery, with anatomic and non-anatomic liver resections widely implemented, as well as liver transplantation in well-selected individuals. Nowadays, there is a variety of liver parenchyma transection devices used by hepatobiliary surgeons in specialized centers, which has significantly improved postoperative outcomes in HCC patients. Therefore, hepatectomy is considered safe and feasible and should be the main therapeutic option for HCC patients, candidates for resection. Liver resection utilizing cavitron ultrasonic aspirator in combination with bipolar radiofrequency ablation is safe and effective for the treatment of HCC with favorable clinical and oncological outcomes.

**Keywords:** Hepatocellular Carcinoma, cirrhosis, surgical treatment, liver resection, technique, outcomes

#### **1. Introduction**

The evolution and development of the surgical techniques utilized during liver resection for Hepatocellular Carcinoma (HCC) are largely an account of the efforts to minimize bleeding during liver parenchymal transection. There is a close relation between blood loss and unfavorable outcomes during liver resection. The modern era liver transection techniques are based on notable advances in solid organ imaging (Computed Tomography, Magnetic Resonance Imaging, Ultrasound), vastly improved anesthetic management, enhanced knowledge of segmental liver anatomy as described by Couinaud [1], refined surgical techniques with notable appreciation of the functional reserve of the liver remnant, as well as the liver regeneration process [2].

Major hepatectomies had been associated with mortality rates of up to 20% during 1990's, and excessive bleeding was an important and common cause of

operative mortality [3]. However, liver resection can now be accomplished with mortality rates of less than 2% in most specialized hepato-pancreato-biliary (HPB) centers [4].

While better patient selection and improved assessment of functional liver remnant are important factors [5], reduced blood loss and the diminishing need for blood transfusion have been additional reasons for improved peri-operative outcome [6]. Other advances in operative technique, including improved delineation of the optimal transection plane with intra-operative ultrasound [7] and the benefit of intermittent inflow occlusion, have also contributed to a reduction in blood loss during major liver resections [8].

The technique of parenchymal transection in hepatic resection has been a topic of great debate for decades worldwide. Finger fraction and clamp-crush techniques have been presented more than fifty years ago and have established as standard approach for liver transection. Significant technological improvements over the past thirty years have led to utilization and adoption of specific surgical instruments and devices for liver transection, such as radiofrequency ablation (RF), ultrasonic cavitron aspirators (Cusa), bipolar sealers (Aquamantis), bipolar energy devices (Ligasure), ultrasonic dissectors (Harmonic), water jet and Tissue link, amongst others [5, 9, 10].

### **2. Prehistory of liver surgery (1886–1950)**

Liver surgery has been a huge chapter in modern surgery and more groundbreaking evolution is still yet to come. Its meaningful to review the beginning of hepatic resections that were reported in the 19th century and follow the journey up to modern times and the techniques that are used today.

The first hepatic operation was done and reported back in 1886 by Lius. He achieved the first partial hepatectomy to a patient with a hepatic adenoma. Reportedly, the use of sharp instruments and Paquelins cautery were utilized for this operation. Unfortunately, post -op hemorrhage was uncontrollable, and the patient died. It is interesting to note that even back in the 19th century, the use of cautery by liquid means was prominent [11].

Following the pioneer of hepatic surgery, Bruns (1888- metastatic liver cancer) and von Eiselberg (1893-hemangioma) attempted hepatectomies. Furthermore, Keen described in 1899 a liver wedge resection in 3 of his patients [12]. In 1891 Lucke achieved the first successful left lobar liver carcinoma excision [13]. In 1908 a very famous physician, whose technique is predominantly used around the world today in hepatic operations, Doctor Pringle, performed abdominal operation in 4 patients with hepatic bleeding of traumatic cause. He managed to control the hemorrhage by clamping the hepatic vein and artery. Only 1 patient survived after this maneuver [14].

In 1911 Wendel reported the first successful right hepatectomy in a 44-year-old woman. He followed the instructions of Cantlie's functional anatomy in detail. Primarily hilar dissection and ligation of right hepatic artery and right hepatic duct was achieved, and furthermore dissection through the quite avascular plane described by Cantlie was performed. Only a year later, Lin applied a new technique. The goal was to resect and destroy liver parenchyma with minimal damage to vessels. This concept will be followed over the years up to present times. The use of the "finger fracture method" served such purpose by resecting parenchyma and leaving vessels undamaged and ready for ligation [15].

As years passed by, it is more evident that 5 historic factors from 1950 and onwards played a role and shaped liver surgery, especially for hepatocellular

*Surgical Therapy of Hepatocellular Carcinoma: State of the Art Liver Resection DOI: http://dx.doi.org/10.5772/intechopen.100231*

carcinoma, as we know it today. Primarily the ability of bleeding control in liver trauma gave confidence to surgeons to proceed in large resections. Secondly, the control of blood supply and drainage of the liver to a more specific level rather than gross ligation of large vessels. The advance in supportive medicine such in fluid balance, adequate anesthesia, respiratory support, and hemodynamics played a key role in a successful operation. Following these, the advancement of imaging modalities and the multimodality team approach in treatment algorithm of HCC.

#### **3. Multi-modality treatment of HCC**

HCC remains the leading cause of cancer related mortality worldwide [16]. Hepatitis C is the most frequent risk factor for HCC in the Western world. On the other hand, chronic hepatitis B infection is the main risk factor in East Asia and sub-Saharan Africa, where incidence rates of HCC are the highest [17]. The MDT can establish patient access to well-established, as well as new multimodality therapies, consulting with all the involved specialists. These emerging therapeutic algorithms have led to review and updates of the treatment management in primary hepatobiliary cancers. Surgery remains the most-effective curative option for all primary hepatobiliary cancers; however, not all patients are good surgical candidates at the diagnosis, due to advanced disease. The Hepatobiliary MDT is crucial for ensuring that other treatment modalities are considered (palliation – best supportive care). This approach can optimize patient care, both on curative and palliative ways. HCC screening has undoubtedly helped earlier detection of tumors, allowing prompt commencement of treatment, positively impact on patients' outcomes [18].

#### **4. Evolution of imaging modalities**

Although current management guidelines for HCC do not require biopsy to prove the diagnosis, lesions greater than 2 cm on MRI or Computed Tomograph Angiography (CTA) scans, with elevated AFP (more than 400 ng/mL) or AFP incrising within sequential measurements, do not require pathologic confirmation according to the guidelines of the European Association for the Study of the Liver (EASL) [19].

According to American Assosiation of Liver Diseases (AASLD) guidelines, liver nodules detected on abdominal US, measuring less than 1 cm should be re-examined twice a year. If no radiological alteration of the hepatic lesion has occurred during a period of up to 2 consecutive years, routine surveillance should be considered.

Every suspicious lesion in high-risk population, with suggestive US-findings for HCC, should be further studied with additional imaging modalities. This radiology workup should include a 4-phase multidetector CT scan or dynamic contrast enhanced MRI. If the tumor has all the typical characteristics of HCC, it should be treated as HCC. If a liver nodule compatible with HCC is greater 2 cm at the initial diagnosis after one dynamic imaging study, biopsy is not mandatory. However, if the vascular profile of the lession on imaging studies of a non-cirrhotic patient is not compatible with HCC, a second imaging study or biopsy of the lesion should be performed to secure the correct diagnosis. If the biopsy is negative for HCC, patients should be further surveilled *via* an abdominal US every 3–6 months, until the lession presents enlarged or with altered imaging characteristics. According to the guidelines of the Asia-Pacific Association for the Study of the Liver 2010 [20],

every liver lesion with non-typical vascular features should be further investigated with other modalities, such as endoscopic ultrasound (EUS).

It is well established that contrast-enhanced CT scans and MRI scans can be performed to examine, differentiate, and investigate a liver lesion. HCC has commonly a unique imaging array [21]. High arterial-phase contrast uptake followed by rapid washout in late phase are common in contrast-enhanced CT and MRI scans; these characteristics may not be present in earlier stages or in not well-differentiated tumors. Triphasic CTA can identify more lesions; however, in patients with nodular cirrhosis, contrast-enhanced MRI should be performed. Tumors sizing between 1 and 2 cm in cirrhotic patients, should be further studied with triphasic CTA and MRI to exclude HCC [22].

#### **5. Anesthesiology management**

During the last century, huge technological and medical advance aid surgeons to easier define their objective rather carefully and to overcome the shrieks and wails of their awake patients as in past times. Anesthesia of modern times came of age, so that the operating rooms became well-orchestrated exhibitions of joint expertise and support. We can now safely say that all matters are now a concern of the anesthetists; they furnished the hemodynamic support for complex operations, as liver surgery. Consequently, surgeons were allowed to focus on their meticulous procedures.

Matters of special interest are conditions that can cause an elevation of right-side cardiac and central venous pressure (CVP), which can significantly increase the risk of intra-operative bleeding. Invasive arterial and CVP monitoring allows for better hemodynamic control and regular blood sampling. All patients may benefit from cardiac output monitoring, enabling greater stability during the cardiovascular changes associated with vascular occlusion during hepatic resection. Core temperature should be monitored and normothermia maintained using warmed-fluids and forced warm-air blankets. Intra-operative coagulation profile should be monitored and corrected with fresh frozen plasma or/and coagulation factors, as indicated from laboratory results. Neuromuscular block should be also monitored [23].

#### **6. Surgical approach**

It well established that in patients without impaired underlying liver status (cirrhosis), an anatomical resection should be accomplished. Major hepatectomies can include up to two-thirds of the functional parenchyma. For cirrhotic patients, due to impaired liver regeneration process, resection is generally minimized to smaller hepatectomies, to maintain adequate liver function. Hypertrophy of the future liver remnant can be achieved with the use of pre-operative portal vein embolization (PVE).

One of the most important key factors during liver resection of HCC is the utilization of intra-operative ultrasound (IOUS), to identify tumor location, margins and its relation to the inflow and outflow vascular structures. The definition of a proper surgical strategy is important not only for achieving an adequate tumor-free margin, but also for avoiding inadvertent injuries to major intrahepatic vessels or bile duct pedicles during dissection or resection.

Management of hepatic inflow through the portal vein and/or vena cava, and hepatic outflow through the hepatic veins, can be routinely performed with control *Surgical Therapy of Hepatocellular Carcinoma: State of the Art Liver Resection DOI: http://dx.doi.org/10.5772/intechopen.100231*

of this vessels. Controlling of the vascular inflow (Pringle maneuver) as an alternative to total vascular occlusion, has decrease deleterious effects of liver ischemia. Ischemic preconditioning of the liver has recently been proposed as a hepatoprotective measure, consisting of application of a brief period of ischemia (10 min) and reperfusion (10 min) after which, a prolonged-period of the liver inflow occlusion can be safely supported. In a prospective series, comparing major liver resections using the Pringle maneuver lasting 30–60 min, an advantage was found of ischemic preconditioning in young patients (<60 years), as well as in patients with steatosis or cirrhosis. Intermittent Pringle occlusion can be well tolerated by cirrhotic patients for up to 60 minutes, and is better tolerated than continuous clamping. The use of low CVP (less than 5 mm Hg) is also of great importance.
