**3.2 Limited hepatectomies**

*Liver Disease and Surgery*

**86**

**Figure 7.**

years [87].

**Figure 6.**

bleeding risk makes the procedure safer.

*NAFLD, surgical sample showing a 11-cm HCC.*

disadvantages of the robot is its cost [88, 89].

of liver impairment in cirrhotic and hepatopathic patients [90].

*(A) Dissection of liver hilum. Elements are indicated by arrows: choledocus (green), portal vein (blue),* 

Minimally invasive liver surgery has strongly progressed during the last 20

*(A) Large HCC In non-cirrhotic live requiring right hepatectomy. (B) Extended right hepatectomy in* 

*Laparoscopic approach* is proven as being safe and presents good outcomes in terms of hospitalization and morbidity. However, the main disadvantage of this approach is the lack of control when a huge bleeding occurs, but the LHM reducing

*Robotic-assisted resection* is the newest technology in hepatobiliary surgery. Compared to laparoscopy, robotic instruments allow wide-angle rotation; therefore, it is easier and faster to perform sutures and ligatures. Four-arm *da Vinci Si* enables the surgeon to perform safer resections, reduced bleeding and major dexterity, particularly in hilar time and in vena cava detachment time. One of the major

HCC is a fast-spreading tumor, particularly in the vascular system; therefore, major resections in large or multinodular tumors allow the most radical removal; however, consistent volume of the functioning liver is also resected, increasing risks

*hepatic artery (black). (B) Caval detachment in bisegmentectomy (VI–VII).*

Limited hepatectomy means resection of two or less segments of Couinaud, like left lobectomy, involving segments II and III, and bisegmentectomy of VI–VII and VI–V, that are the most common (**Figure 8**). Limited hepatectomies are indicated in the case of single or multiple HCC nodules located in one or two adjacent liver segments [69], especially when early diagnosed. Otherwise non-followed up patients are often diagnosed with advanced or multinodular HCC, which are eligible to more extended hepatectomies only.

Limited hepatectomies tend to preserve liver function, so analysis of FRLF and FRLV is often unnecessary in healthy patients, while it is mandatory in compensated cirrhosis due to higher resection risk and distorted liver anatomy [73].

Limited resection is often performed with mini-invasive surgical technique, such as laparoscopic- or robot-assisted surgery. Although expert surgeons are able to resect safely even posterior and subdiaphragmatic lesions, these techniques have some limits. Laparoscopy, in fact, has prolonged surgical times for liver mobilization due to difficulties in parenchyma manipulation, arduous bleeding control and necessity of a major experience of the surgeon.

Robotic liver resection (RLR) allows to go beyond laparoscopic disadvantages, thanks to superior flexibility of its arms. For this reason, RLRs are considered safe, even in deep parenchyma or posterior segment [89]. It is comparable to open approach considering the oncological radicality, but it presents the same advantages of laparoscopy in terms of length of hospital stay and postoperative complications. Conversion rate from robotic to open approach ranges from 0 to 8.8% [87].

Open surgery shall be chosen in the case of contraindications to other approaches such as respiratory impairment that is worsened by pneumoperitoneum or excessive difficulties in liver manipulation; the surgeon's experience remains an important variable in surgical indications, and safety of intervention shall always drive the choice [82, 84].

Nonanatomic liver resection, or wedge resection, is reserved for early HCC (BCLC 0 or A), particularly in the elderly, suffering from advanced cirrhosis or exophytic lesions in hypertrophic segments, where anatomic resection would determine too extensive healthy parenchyma loss [75].

**Figure 8.** *Anatomic resection of segment VI in cirrhotic live. HCC diameter 2.5 cm.*

#### **3.3 Staged hepatectomies**

Staged hepatectomies in HCC treatment are the most recent innovation, first introduced to treat multiple colorectal metastases, now under evaluation for extended hepatectomies in advanced HCC patients [91]. The main issue related to this technique is that most HCC patients are cirrhotic or hepatopathics, and cirrhosis limits parenchyma regeneration in a significant way [91, 92].

Extended resection is feasible when the future remnant liver is ≥40% for cirrhotic patients, ≥30% in patients with severe steatosis or fibrosis without cirrhosis and ≥20% in those with normal liver function [93].

Several strategies can be carried out in order to increase future remnant liver volume (FRLV), improve resectability and reduce postoperative risk of liver failure (PLF) in patients with inadequate FRLV. These techniques include preoperative portal vein embolization (PVE) or ligation (PVL), sequential transarterial chemoembolization and PVE, two-stage hepatectomy (TSH), preoperative Yttrium-90 ( 90Y) radioembolization (RE) and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) [93]. Parenchyma hypertrophy shall be assessed using CT volumetry before performing second-stage hepatectomy [94].

ALPPS is indicated in non-cirrhotic patients with insufficient remnant liver or in the case of PVE failure [93, 95, 96]. This procedure allows higher and faster hypertrophy rates compared to other strategies, due to parenchyma transection and collateral portal branches ligation, especially in hepatopathics; such advantages have been seen also in cirrhotic patients [92]. Moreover, it reduces risk of HCC progression thanks to the shorter time interval between operations. On the other hand, it is associated with high risk of PLF (27%) probably due to portal hyperperfusion, major perioperative complications and mortality [97]. Some authors suggest that the use of anterior approach combined with hanging manoeuver allows higher control and safety during ALPPS procedure [92]. Only few case series have been published about staged hepatectomy for HCC, more perspective research is still necessary, even if this technique is proofing effective and beneficial in selected patients [98].

#### **3.4 Complication**

Postoperative complications have higher incidence and severity in cirrhotic patients [99].

Postoperative live failure (PLF) is the most life-threatening complication following hepatic resection, especially in cirrhotics [93]. It is defined as the decrease in liver synthetic, excretory and/or detoxifying functions after resection [100]. It can be associated with insufficient future liver volume, prolonged operative time, prolonged ischemia, massive intra- and postoperative bleeding, hemodynamic instability, bile duct obstruction, drug-induced injury, viral reactivation and sepsis [90]. It occurs after the fifth day in 4–19% of cases, and it is characterized by various symptoms and signs, such as ascites, pleural effusion, prolonged cholestasis, coagulation disorders, elevated serum lactate levels, hyperbilirubinemia, hypoalbuminemia, hypoglycaemia and hepatic encephalopathy [90, 93].

Bile leakage is another severe postoperative complication. It occurs in 4–17% of cases with comparable incidences in laparoscopic and open approaches [101]. It can induce further complications, such as extrahepatic abscess, requiring reoperation; otherwise it is usually managed with interventional radiology [100].

Postoperative ascites is common, and it may be caused by portal flow resistance increase and serum albumin loss. It can be treated with diuretics, sodium restriction or albumin infusion [100]. Persistent ascites is associated to higher risks of spontaneous bacterial peritonitis (SBP) and mortality.

**89**

**Table 4.**

*Wen et al. [70].*

*Risk factors of postoperative recurrence.*

*HCC in Cirrhotic and Non-cirrhotic Liver: Timing to Surgery and Outcome - State of the Art*

Surgical site infection may occurs within 30 days after resection [100]. Postoperative pneumonia and respiratory disturbs (acute lung injury, acute respiratory distress syndrome) rarely occur after liver resection, especially in the

as ascites, pleural effusion and hospital-acquired infections [87, 99, 102].

ered while planning postoperative surveillance (**Table 4**) [70].

Surgical factors Non-anatomical resection

Clinicopathological factors Low tumor differentiation

Resected patients shall be rapidly mobilized postoperatively; feeding shall start early, together with intravenous liquid restriction. Nonadequately selected patients may also suffer from postoperative acute renal failure or hepatorenal

HCC recurrence within 5 years after hepatic resection occurs in 40–70% of patients [70, 103, 104]. Several recurrence risk factors should be carefully consid-

Intrahepatic recurrent HCC can develop from an intrahepatic metastasis (IM type) or arise from de novo multicentric carcinogenesis (MO type) due to the underlying chronic liver disease. These two HCC types can be distinguished according to their clinic-pathological characteristics and recurrence-free interval [70]. Early recurrence occurs within 2 years from primary resection, and they seem associated with intrahepatic metastasis, whereas late recurrences can show up more than 2 years after surgery, and they are linked to multicentric occurrence [105]. Differentiating them is important because MO, compared to IM, is associated

with higher survival rate after repeated resection and better prognosis [106]. RHCCs have the same imaging features of primary HCC, so they shall be detected and diagnosed using the same methods of primary HCC diagnosis. US, CT or MRI and AFP determination should be performed after surgical

Positive histologic margin (R1 or R2)

Iatrogenic tumor escape or rupture

Adjacent organ invasion satellite lesion High level of AFP before operation Increased AFP level 2 months after operation

Patient's factor Underlying chronic liver disease: active hepatitis infection or cirrhosis

Advanced tumor stage Tumor rupture, damaged capsule Tumor diameter > 5 cm Tumor number ≥ 3 Vascular tumor thrombus Lymph node invasion

Necessity of transfusion due to significant bleeding

Mini-invasive surgical approaches allow lower postoperative complications, such

Clotting disorders are frequent after extended hepatectomies and in cirrhotic patients, who may already have preoperative low platelet count. They can manifest as PT and aPTT prolongation, increase in levels of fibrinogen degradation products

*DOI: http://dx.doi.org/10.5772/intechopen.86638*

and platelet levels reduction [100].

elderly [100].

syndrome [100].

**4. Follow-up**

resection.

*HCC in Cirrhotic and Non-cirrhotic Liver: Timing to Surgery and Outcome - State of the Art DOI: http://dx.doi.org/10.5772/intechopen.86638*

Clotting disorders are frequent after extended hepatectomies and in cirrhotic patients, who may already have preoperative low platelet count. They can manifest as PT and aPTT prolongation, increase in levels of fibrinogen degradation products and platelet levels reduction [100].

Surgical site infection may occurs within 30 days after resection [100].

Postoperative pneumonia and respiratory disturbs (acute lung injury, acute respiratory distress syndrome) rarely occur after liver resection, especially in the elderly [100].

Resected patients shall be rapidly mobilized postoperatively; feeding shall start early, together with intravenous liquid restriction. Nonadequately selected patients may also suffer from postoperative acute renal failure or hepatorenal syndrome [100].

Mini-invasive surgical approaches allow lower postoperative complications, such as ascites, pleural effusion and hospital-acquired infections [87, 99, 102].

#### **4. Follow-up**

*Liver Disease and Surgery*

(

**3.4 Complication**

patients [99].

**3.3 Staged hepatectomies**

Staged hepatectomies in HCC treatment are the most recent innovation, first introduced to treat multiple colorectal metastases, now under evaluation for extended hepatectomies in advanced HCC patients [91]. The main issue related to this technique is that most HCC patients are cirrhotic or hepatopathics, and cirrho-

Extended resection is feasible when the future remnant liver is ≥40% for cirrhotic patients, ≥30% in patients with severe steatosis or fibrosis without cirrhosis

Several strategies can be carried out in order to increase future remnant liver volume (FRLV), improve resectability and reduce postoperative risk of liver failure (PLF) in patients with inadequate FRLV. These techniques include preoperative portal vein embolization (PVE) or ligation (PVL), sequential transarterial chemoembolization and PVE, two-stage hepatectomy (TSH), preoperative Yttrium-90

90Y) radioembolization (RE) and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) [93]. Parenchyma hypertrophy shall be assessed

ALPPS is indicated in non-cirrhotic patients with insufficient remnant liver or in the case of PVE failure [93, 95, 96]. This procedure allows higher and faster hypertrophy rates compared to other strategies, due to parenchyma transection and collateral portal branches ligation, especially in hepatopathics; such advantages have been seen also in cirrhotic patients [92]. Moreover, it reduces risk of HCC progression thanks to the shorter time interval between operations. On the other hand, it is associated with high risk of PLF (27%) probably due to portal hyperperfusion, major perioperative complications and mortality [97]. Some authors suggest that the use of anterior approach combined with hanging manoeuver allows higher control and safety during ALPPS procedure [92]. Only few case series have been published about staged hepatectomy for HCC, more perspective research is still necessary, even if this technique is proofing effective and beneficial in selected patients [98].

Postoperative complications have higher incidence and severity in cirrhotic

Postoperative live failure (PLF) is the most life-threatening complication following hepatic resection, especially in cirrhotics [93]. It is defined as the decrease in liver synthetic, excretory and/or detoxifying functions after resection [100]. It can be associated with insufficient future liver volume, prolonged operative time, prolonged ischemia, massive intra- and postoperative bleeding, hemodynamic instability, bile duct obstruction, drug-induced injury, viral reactivation and sepsis [90]. It occurs after the fifth day in 4–19% of cases, and it is characterized by various symptoms and signs, such as ascites, pleural effusion, prolonged cholestasis, coagulation disorders, elevated serum lactate levels, hyperbilirubinemia, hypoalbu-

Bile leakage is another severe postoperative complication. It occurs in 4–17% of cases with comparable incidences in laparoscopic and open approaches [101]. It can induce further complications, such as extrahepatic abscess, requiring reoperation;

Postoperative ascites is common, and it may be caused by portal flow resistance increase and serum albumin loss. It can be treated with diuretics, sodium restriction or albumin infusion [100]. Persistent ascites is associated to higher risks of sponta-

minemia, hypoglycaemia and hepatic encephalopathy [90, 93].

neous bacterial peritonitis (SBP) and mortality.

otherwise it is usually managed with interventional radiology [100].

using CT volumetry before performing second-stage hepatectomy [94].

sis limits parenchyma regeneration in a significant way [91, 92].

and ≥20% in those with normal liver function [93].

**88**

HCC recurrence within 5 years after hepatic resection occurs in 40–70% of patients [70, 103, 104]. Several recurrence risk factors should be carefully considered while planning postoperative surveillance (**Table 4**) [70].

Intrahepatic recurrent HCC can develop from an intrahepatic metastasis (IM type) or arise from de novo multicentric carcinogenesis (MO type) due to the underlying chronic liver disease. These two HCC types can be distinguished according to their clinic-pathological characteristics and recurrence-free interval [70].

Early recurrence occurs within 2 years from primary resection, and they seem associated with intrahepatic metastasis, whereas late recurrences can show up more than 2 years after surgery, and they are linked to multicentric occurrence [105].

Differentiating them is important because MO, compared to IM, is associated with higher survival rate after repeated resection and better prognosis [106].

RHCCs have the same imaging features of primary HCC, so they shall be detected and diagnosed using the same methods of primary HCC diagnosis.

US, CT or MRI and AFP determination should be performed after surgical resection.


#### **Table 4.**

*Risk factors of postoperative recurrence.*

#### *Liver Disease and Surgery*

US should be performed every 6 months within the first 5 years after surgical treatment; a second level imaging study is requested at the first year and repeated after 12–18 months according to the underlying liver status [5]. Resected patients for HCC, who received direct-acting antiviral (DAA) therapy for HCV negativization, are commonly kept in a less intensive follow-up with US every 12–18 months, for a persistent recurrence risk is maintained [107].

Once detected, RHCC shall be carefully assessed in order to plan the best therapy. Re-resection is the treatment of choice if nodule is resectable and patient is eligible for surgery; so, disease-free time, performance status, future remnant liver volume and function, cirrhosis, portal hypertension and other aspects should be evaluated again before repeating operation. Only about 20% of patients with recurrent HCC receive surgical treatment [105]. Multiple resections could be performed after major or limited primary hepatectomy [70, 108].

Both open and laparoscopic resections can be carried out, but laparotomy is generally preferred, since intra-abdominal adhesions limit laparoscopic approach [109]. Five-year survival rate higher than 70% can be achieved in well-selected patients, despite repeated treatments [103, 104].

Prognosis after repeated resections is linked to clinic-pathological characteristics of primary HCC and recurrence interval. Particularly a disease-free period longer than 1 year after primary resection, single primary HCC and negative portal invasion are positive prognostic factors after second resection [105, 108].

Other possible locoregional therapies for recurrent illness are RFA, MWA and TACE. Liver transplantation could be taken into account in selected patients with worsened liver function and falling within transplant criteria [70, 103].

Incidence of extrahepatic metastases (EHM) after hepatectomy is low (range 5–20%) [108, 110]. High-serum alpha-fetoprotein levels, after liver resection or transplant, is suspicious for extrahepatic recurrence; thus serial cross-sectional total body imaging is mandatory to identify them, and palliative R0 resection may be performed in fit patients with quality of life and survival benefits [27].
