**Table 3.**

*CLIP score evaluation system.*

**Figure 2.** *BCLC staging. Galle et al. [5].*

cases, especially in early stages [41]. PIVKA-II is another serum marker still under evaluation in combination with US for screening purposes, even if not enough evidences have been published yet to justify its use [48].

US is useful to evaluate liver status while planning treatment and to identify possible contraindication to surgery, such as portal vein thrombosis [5].

Contrast-enhanced ultrasound (CEUS) uses gas microbubbles as a contrast agent that highlights lesions with well-represented vasculature. Due to pulmonary clearance, it is suitable for patients with reduced renal function or renal failure. It is repeatable, noninvasive and without risks [49].

**81**

**2.4 MRI**

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

known nodules. HCC is characterized by arterial-phase enhancement and low and later wash-out (after at least 60 seconds) on CEUS [50, 51]. It may differentiate HCC from other nodules in cirrhotic liver and distinguish neoplastic portal vein thrombosis from a benignant one [49]. However CEUS does not detect small (<20 mm) and deep-located lesions, and it hardly discriminates between HCC and

CEUS alone is not enough neither for diagnosis nor for staging of HCC, so it shall be considered as a second-line method in patients unfit either for contrast CT (due to chronic kidney disease) or MRI (due to possible vascular metallic devices or

CT is a second-line imaging technique that enables a high diagnostic accuracy, if proper technique and contrast administration are applied. The CT appearance of HCC is extremely variable and depends on growth pattern (solitary, multifocal

Hepatocellular carcinoma (HCC) is most often hypoattenuating on unenhanced

Based on the guidelines, these diagnostic criteria are sufficient for a noninvasive

HCC could also present atypical findings such as hypervascular lesion without wash-out or hypovascular tumor: hypovascular nodules are not uncommon, and they usually represent early stages like dysplastic nodules with focal HCC or well-

Perfusion CT (PCT) allows quantitative evaluation of tumor-related angiogenesis, tissue perfusion and segmental hepatic function. Higher radiation dose and

CT with higher spatial resolution is fundamental in preoperative management: firstly, in detection of vascular or bile ducts anatomical variants and also in calculation of the future remnant liver (FRL) if a major resection is considered [54]. Evaluation of anatomical variation is critic while planning hepatic resections. Hepatic arterial anatomy variations are common (approximately 45%), and different hepatic venous anomalies, such as drainage of segment VIII into the middle hepatic vein, of segments V and VI directly into the inferior vena cava and of accessory middle hepatic vein directly into the inferior vena cava, can impact surgery. Also portal vein variants and biliary anatomy variations should be carefully investigated [55]. The FRL is calculated by dedicated software that analysed the total liver volume, the tumour volume and the liver volume after surgical procedure. The FRL volume of 20–30% is the lowest limit for a safe resection in healthy livers, 40% in elderly, whereas in patients with diffuse liver disease, a volumetric evaluation shall be associated with FRL function assessment (e.g. indocyanine green retention test or

scan. After contrast agent injection, HCC is typically hypervascular during the arterial phase: small lesions show more homogeneous enhancement than larger neoplasms that are heterogeneous. During the portal venous phase, HCC becomes iso- to hypoattenuating to the surrounding liver. On delayed phase the tumors wash

masses of infiltrating neoplasm), size and histologic composition [52].

out more rapidly than the hepatic parenchyma [45].

lower resolution are the main limitations of this method [45].

Differently from US, CEUS is not indicated for screening but for characterizing

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

cholangiocarcinoma (CCC) [5, 45].

claustrophobia) [50].

diagnosis of HCC [5].

differentiated small HCCs [53].

liver maximum capacity test) [54, 56, 57].

MRI is superior to CT for the diagnosis of HCC [53].

**2.3 CT evaluation**

*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*

Differently from US, CEUS is not indicated for screening but for characterizing known nodules. HCC is characterized by arterial-phase enhancement and low and later wash-out (after at least 60 seconds) on CEUS [50, 51]. It may differentiate HCC from other nodules in cirrhotic liver and distinguish neoplastic portal vein thrombosis from a benignant one [49]. However CEUS does not detect small (<20 mm) and deep-located lesions, and it hardly discriminates between HCC and cholangiocarcinoma (CCC) [5, 45].

CEUS alone is not enough neither for diagnosis nor for staging of HCC, so it shall be considered as a second-line method in patients unfit either for contrast CT (due to chronic kidney disease) or MRI (due to possible vascular metallic devices or claustrophobia) [50].

#### **2.3 CT evaluation**

*Liver Disease and Surgery*

**Figure 2.**

*BCLC staging. Galle et al. [5].*

cases, especially in early stages [41]. PIVKA-II is another serum marker still under evaluation in combination with US for screening purposes, even if not enough

US is useful to evaluate liver status while planning treatment and to identify

Contrast-enhanced ultrasound (CEUS) uses gas microbubbles as a contrast agent that highlights lesions with well-represented vasculature. Due to pulmonary clearance, it is suitable for patients with reduced renal function or renal failure. It is

possible contraindication to surgery, such as portal vein thrombosis [5].

*Modified indications in BCLC staging. Source: Torzilli et al. [35] and Bolondi et al. [37].*

evidences have been published yet to justify its use [48].

repeatable, noninvasive and without risks [49].

**80**

**Figure 3.**

CT is a second-line imaging technique that enables a high diagnostic accuracy, if proper technique and contrast administration are applied. The CT appearance of HCC is extremely variable and depends on growth pattern (solitary, multifocal masses of infiltrating neoplasm), size and histologic composition [52].

Hepatocellular carcinoma (HCC) is most often hypoattenuating on unenhanced scan. After contrast agent injection, HCC is typically hypervascular during the arterial phase: small lesions show more homogeneous enhancement than larger neoplasms that are heterogeneous. During the portal venous phase, HCC becomes iso- to hypoattenuating to the surrounding liver. On delayed phase the tumors wash out more rapidly than the hepatic parenchyma [45].

Based on the guidelines, these diagnostic criteria are sufficient for a noninvasive diagnosis of HCC [5].

HCC could also present atypical findings such as hypervascular lesion without wash-out or hypovascular tumor: hypovascular nodules are not uncommon, and they usually represent early stages like dysplastic nodules with focal HCC or welldifferentiated small HCCs [53].

Perfusion CT (PCT) allows quantitative evaluation of tumor-related angiogenesis, tissue perfusion and segmental hepatic function. Higher radiation dose and lower resolution are the main limitations of this method [45].

CT with higher spatial resolution is fundamental in preoperative management: firstly, in detection of vascular or bile ducts anatomical variants and also in calculation of the future remnant liver (FRL) if a major resection is considered [54].

Evaluation of anatomical variation is critic while planning hepatic resections. Hepatic arterial anatomy variations are common (approximately 45%), and different hepatic venous anomalies, such as drainage of segment VIII into the middle hepatic vein, of segments V and VI directly into the inferior vena cava and of accessory middle hepatic vein directly into the inferior vena cava, can impact surgery. Also portal vein variants and biliary anatomy variations should be carefully investigated [55].

The FRL is calculated by dedicated software that analysed the total liver volume, the tumour volume and the liver volume after surgical procedure. The FRL volume of 20–30% is the lowest limit for a safe resection in healthy livers, 40% in elderly, whereas in patients with diffuse liver disease, a volumetric evaluation shall be associated with FRL function assessment (e.g. indocyanine green retention test or liver maximum capacity test) [54, 56, 57].

#### **2.4 MRI**

MRI is superior to CT for the diagnosis of HCC [53].

At MR imaging small HCCs have variable signal intensity on T1-weighted pre-contrast imaging: they commonly appear hypointense, but high signal intensity has been reported with a frequency ranging between 34 and 61%. On T2-weighted images, HCC is iso- to hyperintense to the surrounding liver parenchyma. Generally, hyperintense lesions on T1 and isointense in T2 are well-differentiated, due to the presence of fat and or glycoprotein; on the contrary lesions hypointense on T1 and hyper on T2 are moderately/poor differentiated. After contrast agent injection, HCC shows the same imaging patterns described on CT examination [45, 58].

The introduction in clinical practice of liver-specific contrast agents, superparamagnetic as well as paramagnetic, significantly improves the detection and characterization of HCC, in particular for lesions between 1 and 2 cm. With paramagnetic contrast agents, the absence of functional hepatocytes, which is considered a sign of malignancy, is represented as a loss of signal intensity during the hepatobiliary phase. Nevertheless, fewer than 20% of well-differentiated and moderately differentiated HCCs appear iso- or hyperintense on hepatobiliary phase images [45, 58].

HCC can rarely invade biliary ducts, both microscopically and macroscopically [59]. Incidence of biliary duct invasion ranges from 1.2 to 9%. It shall be carefully evaluated while staging patients, in order to choose the best treatment and to assess prognosis. Biliary invasion, in fact, is an independent adverse prognostic factor and is often linked to higher biological aggressiveness and portal vein invasion which make prognosis worse [60].

MR cholangiopancreatography (MRCP) is a noninvasive procedure aimed for evaluating the hepatobiliary and pancreatic systems. This method is helpful in assessing biliary invasion. Biliary duct tumor thrombus appears as an intraluminal soft tissue with arterial-phase enhancement on MRCP, and biliary ducts could be seen dilated because of obstructing tumor fragments [60].

Several studies have shown that biliary ducts invasion in HCC is not a contraindication to surgical resection, even in patients with obstructive jaundice caused by biliary tumor thrombus, as long as R0 resection can be achieved. If jaundice is present, biliary drainage should be performed preoperatively [59, 61–63].

MRI also enables the estimation of fat storage in the liver parenchyma: proton density fat fraction (PDFF) technique is a fast, accurate and easy-to-use MR modality that allows liver fat quantification [52].

#### **2.5 Bioptic evaluation**

Biopsy of hepatic lesions is an invasive procedure. Its use is restricted, as a typical pattern in one second-line imaging technique is enough to make an HCC diagnosis, according to the guidelines [64]. In performing liver biopsy, indeed, there is a high risk of bleeding, even higher if the patient has a bleeding disorder due to cirrhosis, and an established possibility of seeding along the needle tract. However, haemorrhagic risk can be reduced with infusion of fresh frozen plasma and platelets before the procedure [51]. Subcapsular and extended tumor and ascites could compromise safe needle insertion too [46].

The procedure allows histological analysis, so it may be used when HCC has atypical growing pattern, so that there is a high suspicion of cholangiocarcinoma (CCC), considering that in such cases bioptic results will impact on therapeutic choice, changing it completely [51].

Furthermore liver parenchyma biopsy is currently the reference procedure for assessing and staging fibrosis and cirrhosis. Stages are classified according to METAVIR score, a histopathologic grading system. Hepatic biopsy has some important limitations: it allows the evaluation of a sample, and not of the entire liver, and, above all, it is an invasive method that could cause minor (temporary pain in 20%

**83**

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

Intraoperative ultrasonography (IOUS) is fundamental while performing hepatic resections. It can give further information about lesions and parenchyma and can determine modifications both in tumor staging and in surgical manage-

IOUS and contrast-enhanced intraoperative ultrasound (CE-IOUS) have higher sensitivity compared to preoperative US and CEUS and allow better detection and

Without these intraoperative procedures, surgical inspection and palpation can overlook up to 50% of preoperatively undetected lesions, especially those located in

Furthermore, IOUS became a mandatory tool in major hepatic surgery, as it allows

Surgical resection is the first-line treatment in non-cirrhotic and compensated cirrhotic livers [5]. The aim of surgery is to achieve R0 resection while preserving enough future remnant liver, in order to avoid postoperative liver failure [68]. Therefore, the most appropriate surgical technique is chosen according to principles of oncological radicality, safety and the least invasiveness [69], considering that HCC tends to be a recurrent disease (recurrence rate 40–70%), and so re-resection

Large nodules, major intrahepatic vessels invasion, portal branches and hepatic vein thrombosis do not contraindicate to surgery as soon as R0 resection can be achieved [71], keeping in mind that a well-preserved liver function is necessary to perform radical hepatic resections [72]. Surgery can be even performed in case of HCV and HBV hepatitis as long as there is metabolic syndrome-related hepatopathy

Patient performance status is also a factor that has to be considered while planning a surgical resection of the liver. Advanced age is not a contraindication, as long as these patients are carefully selected, according to their general condition,

In some cases, surgery may be a *bridging* treatment to liver transplant in patients with advanced cirrhosis and HCC, when waiting time exceeds 6–8 months [74].

Impaired liver function, insufficient future remnant liver, advanced tumor stage and poor performance status are absolute contraindications to surgical resection [73]. Liver resection could not be performed in the case of Child-Pugh > 8, MELD ≥ 9, bilirubin ≥ 3 mg/dl associated with INR ≥ 1.7 or PT < 50%, platelet count < 50,000/μl, indocyanine green retention at 15 minutes >22% and portal vein pressure gradient >10 mmHg without possible TIPS [72, 73]. Extended portal or vena caval thrombosis and extrahepatic disease reveal an advanced HCC stage and contraindicate surgical resection [73]. Patients not eligible for surgery are those with ECOG performance status 4, ASA index > 3, Charlson's index > 3–4 and older than 70 years with comprehensive geriatric assessment (CGA) = 3 or systemic

visualizing of major vessels, assessing their location in relation to HCC lesion and delimiting resection area. It is also important to identify correct dissection planes and accurately define tumor extension, thus to achieve higher rates of R0 resections [67].

of cases) or major (bleeding, sepsis, pneumothorax and even death in 1.1% of cases)

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

characterization of small nodules [66].

deep parenchyma and in cirrhotic liver [67].

or noninvasive treatments are often needed [70].

or cirrhosis is compensated. (Child-Pugh ≤ 8; MELD ≤ 9) [73].

performance status, life expectancy and treatment tolerability [56].

diseases with severe prognosis (life expectancy < 12 months) [56].

complications [65].

ment as well [66].

**3. Surgical treatment**

**2.6 Intraoperative US**

*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*

of cases) or major (bleeding, sepsis, pneumothorax and even death in 1.1% of cases) complications [65].

#### **2.6 Intraoperative US**

*Liver Disease and Surgery*

make prognosis worse [60].

**2.5 Bioptic evaluation**

At MR imaging small HCCs have variable signal intensity on T1-weighted pre-contrast imaging: they commonly appear hypointense, but high signal intensity has been reported with a frequency ranging between 34 and 61%. On T2-weighted images, HCC is iso- to hyperintense to the surrounding liver parenchyma. Generally, hyperintense lesions on T1 and isointense in T2 are well-differentiated, due to the presence of fat and or glycoprotein; on the contrary lesions hypointense on T1 and hyper on T2 are moderately/poor differentiated. After contrast agent injection, HCC

The introduction in clinical practice of liver-specific contrast agents, superparamagnetic as well as paramagnetic, significantly improves the detection and characterization of HCC, in particular for lesions between 1 and 2 cm. With paramagnetic contrast agents, the absence of functional hepatocytes, which is considered a sign of malignancy, is represented as a loss of signal intensity during the hepatobiliary phase. Nevertheless, fewer than 20% of well-differentiated and moderately differentiated HCCs appear iso- or hyperintense on hepatobiliary phase images [45, 58]. HCC can rarely invade biliary ducts, both microscopically and macroscopically [59]. Incidence of biliary duct invasion ranges from 1.2 to 9%. It shall be carefully evaluated while staging patients, in order to choose the best treatment and to assess prognosis. Biliary invasion, in fact, is an independent adverse prognostic factor and is often linked to higher biological aggressiveness and portal vein invasion which

MR cholangiopancreatography (MRCP) is a noninvasive procedure aimed for evaluating the hepatobiliary and pancreatic systems. This method is helpful in assessing biliary invasion. Biliary duct tumor thrombus appears as an intraluminal soft tissue with arterial-phase enhancement on MRCP, and biliary ducts could be

Several studies have shown that biliary ducts invasion in HCC is not a contraindication to surgical resection, even in patients with obstructive jaundice caused by biliary tumor thrombus, as long as R0 resection can be achieved. If jaundice is

MRI also enables the estimation of fat storage in the liver parenchyma: proton density fat fraction (PDFF) technique is a fast, accurate and easy-to-use MR modal-

Biopsy of hepatic lesions is an invasive procedure. Its use is restricted, as a typical pattern in one second-line imaging technique is enough to make an HCC diagnosis, according to the guidelines [64]. In performing liver biopsy, indeed, there is a high risk of bleeding, even higher if the patient has a bleeding disorder due to cirrhosis, and an established possibility of seeding along the needle tract. However, haemorrhagic risk can be reduced with infusion of fresh frozen plasma and platelets before the procedure [51]. Subcapsular and extended tumor and ascites could

The procedure allows histological analysis, so it may be used when HCC has atypical growing pattern, so that there is a high suspicion of cholangiocarcinoma (CCC), considering that in such cases bioptic results will impact on therapeutic

Furthermore liver parenchyma biopsy is currently the reference procedure for assessing and staging fibrosis and cirrhosis. Stages are classified according to METAVIR score, a histopathologic grading system. Hepatic biopsy has some important limitations: it allows the evaluation of a sample, and not of the entire liver, and, above all, it is an invasive method that could cause minor (temporary pain in 20%

present, biliary drainage should be performed preoperatively [59, 61–63].

seen dilated because of obstructing tumor fragments [60].

ity that allows liver fat quantification [52].

compromise safe needle insertion too [46].

choice, changing it completely [51].

shows the same imaging patterns described on CT examination [45, 58].

**82**

Intraoperative ultrasonography (IOUS) is fundamental while performing hepatic resections. It can give further information about lesions and parenchyma and can determine modifications both in tumor staging and in surgical management as well [66].

IOUS and contrast-enhanced intraoperative ultrasound (CE-IOUS) have higher sensitivity compared to preoperative US and CEUS and allow better detection and characterization of small nodules [66].

Without these intraoperative procedures, surgical inspection and palpation can overlook up to 50% of preoperatively undetected lesions, especially those located in deep parenchyma and in cirrhotic liver [67].

Furthermore, IOUS became a mandatory tool in major hepatic surgery, as it allows visualizing of major vessels, assessing their location in relation to HCC lesion and delimiting resection area. It is also important to identify correct dissection planes and accurately define tumor extension, thus to achieve higher rates of R0 resections [67].

#### **3. Surgical treatment**

Surgical resection is the first-line treatment in non-cirrhotic and compensated cirrhotic livers [5]. The aim of surgery is to achieve R0 resection while preserving enough future remnant liver, in order to avoid postoperative liver failure [68]. Therefore, the most appropriate surgical technique is chosen according to principles of oncological radicality, safety and the least invasiveness [69], considering that HCC tends to be a recurrent disease (recurrence rate 40–70%), and so re-resection or noninvasive treatments are often needed [70].

Large nodules, major intrahepatic vessels invasion, portal branches and hepatic vein thrombosis do not contraindicate to surgery as soon as R0 resection can be achieved [71], keeping in mind that a well-preserved liver function is necessary to perform radical hepatic resections [72]. Surgery can be even performed in case of HCV and HBV hepatitis as long as there is metabolic syndrome-related hepatopathy or cirrhosis is compensated. (Child-Pugh ≤ 8; MELD ≤ 9) [73].

Patient performance status is also a factor that has to be considered while planning a surgical resection of the liver. Advanced age is not a contraindication, as long as these patients are carefully selected, according to their general condition, performance status, life expectancy and treatment tolerability [56].

In some cases, surgery may be a *bridging* treatment to liver transplant in patients with advanced cirrhosis and HCC, when waiting time exceeds 6–8 months [74].

Impaired liver function, insufficient future remnant liver, advanced tumor stage and poor performance status are absolute contraindications to surgical resection [73]. Liver resection could not be performed in the case of Child-Pugh > 8, MELD ≥ 9, bilirubin ≥ 3 mg/dl associated with INR ≥ 1.7 or PT < 50%, platelet count < 50,000/μl, indocyanine green retention at 15 minutes >22% and portal vein pressure gradient >10 mmHg without possible TIPS [72, 73]. Extended portal or vena caval thrombosis and extrahepatic disease reveal an advanced HCC stage and contraindicate surgical resection [73]. Patients not eligible for surgery are those with ECOG performance status 4, ASA index > 3, Charlson's index > 3–4 and older than 70 years with comprehensive geriatric assessment (CGA) = 3 or systemic diseases with severe prognosis (life expectancy < 12 months) [56].

Intrahepatic recurrence after surgical treatment is often linked to portal venous invasion, both macroscopic (MPVI) and microscopic (mPVI). MPVI can be preoperatively detected by CT, MRI and US, whereas mPVI is very difficult to diagnose preoperatively. In order to reduce recurrence rates due to mPVI, in young and fit patients, anatomic liver resection (ALR) should be preferred to nonanatomic liver resection (NALR) [75]. ALR should be taken into account especially in patients who have solitary PVI (in a single portal vein branch) or a higher risk of mPVI linked to α-fetoprotein ≥ 20 ng/ml, PIVKA-II ≥ 100 mAU/ml, tumor size ≥ 5 cm and a confluent lesion morphology [76, 77]. Some authors suggest that during anatomic resection, it is better to avoid excessive rotation of the liver, perform an early extrahepatic ligation of the portal pedicle of the resected segment(s) before parenchymal transection and obtain an adequate surgical margin to decrease the risk of recurrences [71].

On the other hand, NALR allows *parenchyma-sparing* surgery that, though associated to higher recurrence rates, is indicated in elderly and cirrhotic patients suffering from early HCC, where an anatomic resection would sacrifice an excessive amount of the parenchyma (**Figure 4**) [75].

Surgery is proved to be superior to RF in terms of local recurrences for nodules >2 cm [19, 78], but in the case of multinodular HCC, in selected patients, they can be combined together to achieve a better outcome, compared to TACE or TARE, whose role remains palliative (**Figure 5**) [35, 64, 78].

#### **3.1 Major hepatectomies**

All liver resections involving three or more liver segments of Couinaud are considered major hepatectomies. Most commonly performed resections are right hepatectomy, left hepatectomy, right-extended hepatectomy, left-extended hepatectomy and median hepatectomy [69]. Major hepatectomy is frequently required to achieve a complete tumor removal (**Figure 6**) [79].

Healthy livers may be resected as much as 70% without major complications; cirrhotic or hepatopathic patients shall be cautiously submitted to resection after precise FRL analysis in terms of future remnant liver function (FRLF) and volume [54]. Liver resections for HCC related to NAFLD and metabolic syndrome are encumbered by important rates of complications (13–20%) and mortality (2%); procedure risk profile in this condition is closer to that burdening cirrhotic livers rather than non-cirrhotic ones [5].

Age is not a contraindication to major hepatectomy, because elderly patients' liver, when healthy, have comparable regeneration rates to younger ones, while patients' performance status and liver residual function are more important [80].

Major hepatectomies can be performed safely in either open or mini-invasive approaches [81].

*Open approach* is more invasive, but it offers great advantages in a better view on the operative field, allowing a complete administration in organ mobilization and a prompt control of bleeding (**Figure 7**). Open approach is indicated in the case of upper abdominal adhesions, respiratory impairment and advanced liver fibrosis. In severe respiratory disease, pneumoperitoneum worsens gas exchange; therefore, laparoscopic- and robot-assisted resection are contraindicated [82]. In the case of upper abdominal adhesions, it is hard to induce an adequate pneumoperitoneum to insert trocars and instrument safely, and open approach is the one indicated [83]. Advanced liver fibrosis makes the organ stiffer and difficult to mobilize with laparoscopic graspers [84]. The *liver hanging manoeuver* (*LHM*), which is a technique of passing a tape along the retrohepatic avascular space and suspending the liver during parenchymal transection, facilitates anterior approach of major hepatectomy and minimizes bleeding by elevation of the liver along its deeper parenchymal plane [85, 86].

**85**

**Figure 5.**

*Intraoperative RF in HCC nodule of II segment.*

**Figure 4.**

*Wedge resection (NALR) in the NAFLD liver. HHC located in V/VIII segment.*

*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*

*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*

**Figure 4.** *Wedge resection (NALR) in the NAFLD liver. HHC located in V/VIII segment.*

**Figure 5.** *Intraoperative RF in HCC nodule of II segment.*

*Liver Disease and Surgery*

amount of the parenchyma (**Figure 4**) [75].

**3.1 Major hepatectomies**

rather than non-cirrhotic ones [5].

approaches [81].

whose role remains palliative (**Figure 5**) [35, 64, 78].

achieve a complete tumor removal (**Figure 6**) [79].

Intrahepatic recurrence after surgical treatment is often linked to portal venous invasion, both macroscopic (MPVI) and microscopic (mPVI). MPVI can be preoperatively detected by CT, MRI and US, whereas mPVI is very difficult to diagnose preoperatively. In order to reduce recurrence rates due to mPVI, in young and fit patients, anatomic liver resection (ALR) should be preferred to nonanatomic liver resection (NALR) [75]. ALR should be taken into account especially in patients who have solitary PVI (in a single portal vein branch) or a higher risk of mPVI linked to α-fetoprotein ≥ 20 ng/ml, PIVKA-II ≥ 100 mAU/ml, tumor size ≥ 5 cm and a confluent lesion morphology [76, 77]. Some authors suggest that during anatomic resection, it is better to avoid excessive rotation of the liver, perform an early extrahepatic ligation of the portal pedicle of the resected segment(s) before parenchymal transection and obtain an adequate surgical margin to decrease the risk of recurrences [71]. On the other hand, NALR allows *parenchyma-sparing* surgery that, though associated to higher recurrence rates, is indicated in elderly and cirrhotic patients suffering from early HCC, where an anatomic resection would sacrifice an excessive

Surgery is proved to be superior to RF in terms of local recurrences for nodules >2 cm [19, 78], but in the case of multinodular HCC, in selected patients, they can be combined together to achieve a better outcome, compared to TACE or TARE,

All liver resections involving three or more liver segments of Couinaud are considered major hepatectomies. Most commonly performed resections are right hepatectomy, left hepatectomy, right-extended hepatectomy, left-extended hepatectomy and median hepatectomy [69]. Major hepatectomy is frequently required to

Healthy livers may be resected as much as 70% without major complications; cirrhotic or hepatopathic patients shall be cautiously submitted to resection after precise FRL analysis in terms of future remnant liver function (FRLF) and volume [54]. Liver resections for HCC related to NAFLD and metabolic syndrome are encumbered by important rates of complications (13–20%) and mortality (2%); procedure risk profile in this condition is closer to that burdening cirrhotic livers

Age is not a contraindication to major hepatectomy, because elderly patients' liver, when healthy, have comparable regeneration rates to younger ones, while patients' performance status and liver residual function are more important [80]. Major hepatectomies can be performed safely in either open or mini-invasive

*Open approach* is more invasive, but it offers great advantages in a better view on the operative field, allowing a complete administration in organ mobilization and a prompt control of bleeding (**Figure 7**). Open approach is indicated in the case of upper abdominal adhesions, respiratory impairment and advanced liver fibrosis. In severe respiratory disease, pneumoperitoneum worsens gas exchange; therefore, laparoscopic- and robot-assisted resection are contraindicated [82]. In the case of upper abdominal adhesions, it is hard to induce an adequate pneumoperitoneum to insert trocars and instrument safely, and open approach is the one indicated [83]. Advanced liver fibrosis makes the organ stiffer and difficult to mobilize with laparoscopic graspers [84]. The *liver hanging manoeuver* (*LHM*), which is a technique of passing a tape along the retrohepatic avascular space and suspending the liver during parenchymal transection, facilitates anterior approach of major hepatectomy and minimizes bleed-

ing by elevation of the liver along its deeper parenchymal plane [85, 86].

**84**

#### **Figure 6.**

*(A) Large HCC In non-cirrhotic live requiring right hepatectomy. (B) Extended right hepatectomy in NAFLD, surgical sample showing a 11-cm HCC.*

Minimally invasive liver surgery has strongly progressed during the last 20 years [87].

*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 bleeding risk makes the procedure safer.

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

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

#### **Figure 7.**

*(A) Dissection of liver hilum. Elements are indicated by arrows: choledocus (green), portal vein (blue), hepatic artery (black). (B) Caval detachment in bisegmentectomy (VI–VII).*

**87**

**Figure 8.**

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

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

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

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

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

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

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

necessity of a major experience of the surgeon.

determine too extensive healthy parenchyma loss [75].

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

**3.2 Limited hepatectomies**

extended hepatectomies only.

8.8% [87].

drive the choice [82, 84].

*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*
