Table of Contents  

Croner: Surgery for primary liver malignancies – innovations and limitations

Background

Primary liver malignancies usually arise from hepatocytes or the bile duct system. The incidence of hepatocellular carcinoma (HCC) is continuing to increase. It is the sixth most common cancer and the third most common cause of cancer-related death worldwide.1,2 The risk of HCC depends on the underlying causes and duration of the disease damaging the liver. HCCs can be the result of hepatitis B and C, or nutritive toxic and metabolic causes. Most HCCs develop in cirrhotic livers (95%).3 They grow as single or multifocal tumours, or as a diffuse mass within the liver, and can spread to regional lymph nodes or distant organs (Figure 1). The treatment of HCCs is an interdisciplinary challenge. Interventional therapy such as transvascular embolization of tumour-feeding arteries or ablation of smaller tumours combined with chemotherapy are treatment options after surgery. The sequence of these therapies depends on the size and the growth characteristics of the tumours.

FIGURE 1

(a) Multifocal HCC of a liver that is not a good candidate for liver resection and (b) solitary HCC of the right liver in the absence of cirrhosis, which underwent right hemihepatectomy.

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Cholangiocarcinomas (CCs) arise from the epithelial cells of the bile duct system and are associated with a poor prognosis. CC is the second most common primary hepatic malignancy worldwide.4 Primary sclerosing cholangitis, fibropolycystic liver disease (Caroli syndrome), parasitic infections, intrahepatic gallstones and hepatitis are risk factors for the development of CCs.4 Patients present with various symptoms depending on the localization of the tumour at the time of presentation. CCs can be intrahepatic or extrahepatic, developing as hilar tumours (Klatskin tumours) within the bile duct system. Symptoms such as abdominal pain or jaundice caused by bile duct obstruction are common. Bile duct drainage may be necessary prior to surgery in septic and high-risk patients. CCs can invade adjacent vessels and spread to regional lymph nodes or distant organs.

Criteria are necessary to identify which patients with primary liver malignancies are suitable for surgery. Vascular involvement of the tumours, distant tumour spread and liver parenchyma damage are contraindications to surgery; however, surgical techniques have improved over time. Vessels can be replaced and reconstructed, and liver parenchyma dissections can be performed with blood-sparing tools. Moreover, minimally invasive techniques have been established that reduce patient morbidity. Therefore, suitability for surgery has been extended over time, but the question remains which patients benefit from which procedure.

Liver resection

Various types of liver resection can be performed in patients with primary liver malignancies. The spectrum ranges from solitary segmental resections to hemihepatectomy, and in selected cases to extended hemihepatectomy. Peritoneal carcinomatosis or distant metastases are clear contraindications to resection. Surgery has risk in patients with reduced liver function; the Child–Pugh classification is a widely used clinical scoring system to measure this issue. Usually Child–Pugh class A patients are candidates for liver resection, and only in selected cases can this be extended to other patients. Liver function should be evaluated prior to surgery in other patients considering surgery. Tests such as the indocyanine green clearance, which is mainly used in Korea and Japan, or the LiMAX test can measure the remnant liver function prior to surgery. Furthermore, real-time fluorescence imaging techniques enable the intraoperative visualization of portal perfusion regions and thereby help to define resection areas. This technique can guide the surgeon and increase precision.5

Solitary or smaller HCCs are good candidates for liver resection (see Figure 1). The tumour size and number are predictors of postoperative outcome.6 Patients with HCCs who meet with the Milan criteria should undergo liver transplantation. The criteria for resectable tumours are defined by the Barcelona Clinical Liver Cancer staging system; patients with HCCs and portal hypertension are not good candidates for liver resection. The perioperative mortality in this group of patients is significantly higher (6.1%) than in cohorts without portal hypertension (2.8%). Morbidity is higher in patients with portal hypertension (41.7%) than in those with normal portal vein pressure (34.7%), and liver failure occurs more frequently.7 The 5-year overall survival rate in patients post surgery for HCC is 47.9% and the disease-free survival rate is 38%.8 In patients with elevated bilirubin and portal hypertension (> 10 mmHg) the 5-year survival rate is < 30%. These two indicators are good predictors for patient outcome after surgery.9 Recently, three serum markers [alpha-fetoprotein (AFP), lens culinaris agglutinin-reactive fraction of AFP and des-γ-carboxy prothrombin] have been described as predictive markers for outcome after liver resection in HCCs. Patients in whom all three markers are increased show significantly decreased disease-free survival compared with patients with lower levels.10 Liver cirrhosis, which is present in 80–90% of patients with HCC, is a further predictor of poor outcome in patients undergoing surgery (Table 1). Major resections can be performed more frequently in candidates without liver cirrhosis; this is why 5-year disease-free survival and overall survival are significantly higher in non-cirrhotic patients.8 Adherent extrahepatic structures that may be invaded by the tumour should be removed by en bloc resection to guarantee clear macroscopic and microscopic resection margins (Figure 2).

TABLE 1

Selection criteria for high- and low-risk cases in patients undergoing liver resection for primary liver malignancies (CC, HCC)

High risk Low risk
Liver cirrhosis No liver cirrhosis
Child–Pugh class B/C Child–Pugh class A
Vascular tumour invasion Portal vein pressure < 10 mmHg
Bile duct tumour thrombosis Normal bilirubin
Portal hypertension > 10 mmHg Solitary tumours
Elevated bilirubin
Multifocal tumours
FIGURE 2

(a) Hepatocellular carcinoma of the right liver with (b) collateral vessels to the superior mesenteric artery and invasion of the right colonic flexure. (c) Multivisceral resection including right colon flexure for tumour invasion and vascular collateralization was necessary.

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The only option for complete cure of CC is liver resection. In most cases hemihepatectomy with or without bile duct reconstruction is preferred. The 5-year survival rate of patients with intrahepatic CC varies between 8% and 47% after surgery.4 Mobilization of tumour-affected bile ducts from liver parenchyma should be avoided because it may lead to tumour cell dissemination and adversely affect patient prognosis; en bloc resection with liver parenchyma is necessary. Patients with Klatskin tumours can undergo liver segment I and IVb resection and partial segmental V resection together with the hilar duct (dumbbell-form resection), which is a parenchyma-sparing procedure. The morbidity of this technique is significantly reduced (26.3%) compared with hemihepatectomy (48.6%). Liver dysfunction is less observed but bile leaks seem to occur more frequently after dumbbell-form resections. The R0 resection rate is similar to dumbbell-form resections and standard procedures, and there is no significant difference in 3- and 5-year survival (32.1% vs. 34.6%; and 21.4% vs. 23.3%).11

Vascular tumour invasion and bile duct thrombosis

Primary liver malignancies can invade neighbouring vessels and bile ducts. In the past, this was a contraindication to surgery; however, resection techniques have improved over time and vascular reconstruction can safely be performed using homo- or xenografts. If partial, tangential vessel removal is necessary and patches can be inserted to maintain the vascular continuity (Figure 3). In the case of complete vascular resection, prostheses can be inserted for vessel replacement. Vascular resection and reconstruction can be classified according to extent. Arteries and veins can be removed and replaced, but it is predominantly veins, such as the vena cava, or the hepatic or portal veins, that are affected. In patients with hilar CCs, portal vein resections are sometimes necessary and the continuity of the vessels can be maintained by the described techniques. The overall morbidity is not increased in patients who undergo liver resection with portal vein resections compared with patients in whom portal vein removal is not necessary.12 The incidence of postoperative bile leakage is not increased during this procedure; liver failure occurs in 11.9% of patients and the mortality rate is 7.3%.12 However, vascular complications such as thrombosis, stenosis and pseudoaneurysms are higher if vessel resection has been performed.13 Although portal vein resection and reconstruction is a safe procedure, the tumour-associated prognosis is poorer in patients with tumour infiltration of the portal vein. Furthermore, patients have a higher risk of perioperative death after arterial resection. However, vascular reconstruction remains a feasible option to increase the rate in patients with advanced tumours.13

FIGURE 3

Cholangiocarcinoma involving the inverior vena cava (IVC). (a) Magnetic resonance image of the liver showing the tumour and (b) intraoperative situs after liver resection and partial resection of the IVC with xenograft patch.

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Bile duct thrombosis is rare in HCC, being reported in 1.2–12.9% of all cases.14 This is a result of direct tumour infiltration into bile ducts or haemobilia. Patients sometimes present with jaundice due to bile duct obstruction. Bile duct thrombosis as a result of vascular invasion is an indicator of advanced stages of poorly differentiated carcinomas. It can be removed by radical surgical procedures, which increase surgery time, but does not improve postoperative morbidity (35%) and mortality (3%). Surgical strategies are not clearly defined for bile duct thrombosis. Anatomical and non-anatomical resections are described.14 When performing surgery it should be considered that non-anatomical resections increase the risk of leaving behind residual tumour. There is no significant difference in survival between patients with or without bile duct thrombosis 1 and 3 years after surgery (1 year: 72% vs. 81%, respectively; 3 years: 40% vs. 55%).14 After a 5-year observation period, overall survival in patients with bile duct thrombosis is significantly lower (16%) than in patients without bile duct thrombosis (45%). However, because perioperative morbidity and mortality are not increased 3 years after surgery, selected patients with bile duct thrombosis should undergo liver resection.14

Lymph node dissection

Primary lymphatic drainage of liver malignancies is via the hepatoduodenal ligament. Further drainage can spread in two compartments: (1) along the common hepatic artery to the coeliac trunk; and (2) in a retroduodenal and retropancreatic direction to the interaortocaval lymph nodes. Lymph node metastases should be expected along these regions and the question remains if extended lymph node dissection of these areas would reduce the risk of a tumour recurrence and increase survival rates. Lymph node dissection is safe and does not increase morbidity in patients undergoing liver resection at the same time. Morbidity rates of 47.4% without and 36.6% with lymph node dissection have been previously reported.15 Lymph node metastases are found mainly along the hepatoduodenal ligament. The presence of lymph node metastases is an indicator of poor survival. In cases where there are lymph node metastases present, the median survival is 28 months, and tumours recur in 82.05% of patients.16 In HCC, 1-, 3- and 5-year overall survival rates without lymph node dissection are 94.7%, 78.9% and 65.8%, respectively, whereas the survival rates with lymph node dissection rates are 87.8%, 78.0% and 70.7%, respectively.15 The 1-, 3- and 5-year disease-free survival rates without lymph node dissection are 81.6%, 68.4%, 63.2%, respectively, and with lymph node dissection are 78.0%, 65.9% and 63.4%, respectively.15

The 1-, 3- and 5-year overall survival rates for intrahepatic CCs are 85.5%, 52.8% and 45.6%, respectively, described for patients with or without lymp node metastases.17 The 5-year survival rate for patients with lymph node metastases is poor and has been reported as 0%, compared with 51% in the case of patients without lymph node metastases; this is a significant difference.20 However, there is no difference in survival between N1, N2 or N3 stages.17 Regional lymph node metastases are described in up to 35% of patients with hilar CCs,18 and the presence of lymph node metastases is significantly associated with poor survival.19 There is no evidence that extended lymph node dissection improves survival of patients with either intrahepatic or extrahepatic CCs.4

Extended lymph node dissection for primary liver tumours is safe and does not significantly increase morbidity; however, it does not improve patients’ survival. It should be performed, when possible, for tumour staging purposes.

Critical liver remnant

Leaving a postoperative liver remnant with adequate function is essential to reduce morbidity and mortality after liver resection. Patients with regular liver function tolerate removal of 70–75% of the liver tissue; however, in the case of primary liver malignancies, liver function is usually impaired as only 5% of tumours occur in non-cirrhotic livers.20 If the predicted liver remnant volume is < 40% in patients with impaired hepatic function and < 60% in those with cirrhotic livers, strategies are needed to guarantee sufficient postoperative liver function.4,20 Several techniques have been described to induce preoperative liver hypertrophy prior to extended liver resection.2123

Ipsilateral portal vein embolization at the site of the tumour in the liver is an intervention that induces contralateral hypertrophy and decreases the risk of postoperative liver failure. Usually the portal vein is punctured percutaneously, a catheter is placed in the vein and embolizing particles are inserted into the vessel. The procedure is safe and can be successfully carried out in about 97% of selected patients.24 In about 24% of patients a post-embolization syndrome may occur, including temporary moderate elevation of liver enzymes, nausea, pain and fever. A median increase in liver volume of 137 ml, measured by computerized tomography, can be expected (Figure 4). Cirrhotic livers increase in volume by 5–10% within 2–3 weeks.25 The function of the remaining liver can be measured by scintigraphic imaging or other functional tests (e.g. indocyanine green clearance, LiMAX) that can predict a patient’s outcome more precisely.21,24,26 After a median interval of 28 days, surgery can be performed. Around 90% of patients can be transferred to surgery after interventional portal vein embolization. Morbidity after surgery in this context is 42% and the mortality rate is 4%.21 It should be noted that, in the case of bilateral tumours, lesions at the non-embolized side grow more rapidly than those at the non-embolized liver side. This is triggered by factors inducing liver hypertrophy. Therefore, portal vein embolization should be considered for cases in which only unilateral tumours are present.

FIGURE 4

(a) Left liver (green) lobe before endovascular embolization of the right portal vein; (b) portal vein before endovascular embolization; (c) left liver (green) lobe 4 weeks after endovascular embolization of the right portal vein; and (d) portal vein after endovascular embolization.

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The portal vein can also ligated by surgery following staged liver resection. This procedure can be performed laparoscopically or by open technique. Morbidity and mortality after portal vein embolization and portal vein ligation are similar. As portal vein ligation may open intrahepatic shunts it was considered to be less effective than portal vein embolization; however, meta-analyses show only borderline differences between the methods.25,27,28 Portal vein ligation is often carried out in patients with bilateral liver tumours in whom staged resection is necessary. During the first operation the surgeon can explore the liver, resect tumours at one side and then perform contralateral portal vein ligation.

A further surgical technique to induce contralateral liver hypertrophy is portal vein ligation with in situ splitting of the liver parenchyma on the right side of the umbilical vein (associated liver partition and portal vein ligation for staged hepatectomy [ALPPS] procedure).29 This procedure enhances liver proliferation and makes it quicker than other techniques. The liver proliferates within a median of 9 days and the left lateral lobes show rapid hypertrophy of up to 75%. However, this procedure is associated with high morbidity and mortality.23 The 90-day mortality rate is 15%, and complications occur in 67% of patients.23 Nevertheless, it can be used as rescue strategy if hypertrophy after portal vein embolization or ligation is insufficient.

Liver transplantation

In patients with HCC, prognosis is determined by tumour growth and the severity of the underlying chronic liver disease. In patients with good liver function, tumour resection is recommended and can be curative. In the presence of liver cirrhosis, resection should be considered carefully. Currently there are no clear international treatment guidelines to indicate whether liver resection or transplantation is preferred in cirrhotic livers.9 Liver transplantation can cure both the tumour disease and the cirrhosis. In patients with HCCs meeting the Milan criteria, liver transplantation is recommended. Liver transplantation has also shown good success in patients who do not meet these criteria although tumour recurrence rates are higher and patient outcome poorer in the latter group.30 The 1- and 5-year overall survival rate of patients meeting the Milan criteria is 84.4% and 59.3%, respectively.31 Similar patient cohorts that undergo liver resection have a 1- and 5-year overall survival of 84.5% and 47.9%, respectively.31 Patients after liver transplantation show a significantly lower 3-year tumour recurrence rate and higher disease-free survival than patients undergoing liver resection (disease-free survival rates of 62% vs. 45.9%).32 Recently, AFP levels > 321 ng/ml and specific cytokeratin 19 and glypican-3 expression patterns in HCCs have been identified as predictors for early tumour recurrence after liver transplantation.33 The feasibility of liver transplantation is limited in some regions because of a shortage of organ donors; to overcome this problem, living donor programmes can be initiated. The 5-year overall and disease-free survival rate of patients receiving organs from living donors is 81.5% and 75.5%, respectively34 but high-risk groups exist. AFP levels > 200 ng/ml and tumours that can be viewed using positron emission tomography have been identified as indicators predicting poor outcome.35 These patients have a 5-year disease-free survival rate of 60% if their tumours meet the Milan criteria and 9.1% if they do not. The outcome after liver transplantation for HCC depends on the selection criteria, and patients should be assessed for suitability individually.

Liver transplantation for CCs should be carried out in selected patients within clinical trials only. The 5-year disease-free survival rate is 45.4% and the 5-year overall survival rate is 41.8%.36 Mean disease-free survival is 7.97 months and mean overall survival 11.7 months.36 Patients with well-differentiated tumours without vascular invasion show a better outcome.37 The Mayo Clinic protocol, which was established in 1993, combines careful patient selection with neoadjuvant tumour treatment following transplantation for early-stage unresectable hilar CCs.35 The maximum size of tumour that can be considered is 3 cm, and no intra- or extrahepatic metastases or gallbladder involvement is permitted. Neoadjuvant therapy includes 4000–4500 cGy external beam radiation followed by 2000–3000 cGy transcatheter irradiation with iridium. Patients receive fluorouracil during the radiation process and later receive capecitabine until liver transplantation. Before transplantation, surgical abdominal exploration is performed, including inspection of the lymph nodes and peritoneum. Patients with tumour deposits in these regions are excluded from transplantation. The 5-year overall survival rate after transplantation of patients completing this protocol is 59–71%.38,39 Transplantation for CCs is controversial and needs responsible selection of suitable patients.

Minimally invasive liver surgery

Minimally invasive techniques have been developed for liver surgery and are an essential part of operative procedures today. Previously, left lateral (segments II and III) and anterior liver segments (segments IVb, V, VI) have been described as being particularly accessible for minimally invasive liver resections; however, techniques have now improved and all liver segments can be removed, isolated or combined by minimally invasive techniques4042 – even a hemihepatectomy, in situ splitting and portal vein ligation or living donor resection for liver transplantation can be performed by a minimally invasive procedure.27 These procedures need highly experienced specialists in liver surgery with a strong knowledge of minimally invasive operations. Patients benefit from all advantages of minimally invasive surgery: they need less pain medication, have smaller incisions and stay in hospital for a shorter period than patients undergoing open procedures.43 Resected specimens can be removed by Pfannenstiel incisions or in case of prior surgery, which is not a contraindication to minimally invasive liver surgery, by opening pre-existing scars (Figure 5).

FIGURE 5

Laparoscopic liver resection. (a) Port placement; (b) parenchyma dissection with Harmonic® scalpel (Ethicon, USA); and (c) postoperative abdomen – the specimen was removed via a Pfannenstiel incision.

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Laparoscopic liver surgery can be carried out by full laparoscopy or using a hand-assisted hybrid technique. Both techniques are safe with reported morbidity of 11% and mortality of 0.3% in selected cases.44 The advantages of the hand-assisted technique are the tactile feedback, facilitation of the liver mobilization, manual control of bleeding and the absence of a separate extraction side incision. The disadvantages are interference of the hand port with the laparoscopy trocars and risk of hernia on the hand port incision side. Nevertheless, the port-assisted technique is a useful method for initiating a minimally invasive liver procedure because of the good liver control during the laparoscopic operation. In comparison with open surgery, patients after laparoscopic surgery perioperatively benefit from less blood loss, less blood transfusion, decreased morbidity and decreased hospital stay, whereas oncological outcomes for 1-, 3- and 5-year survival do not differ between the procedures (Table 2).44 Because of its safety and because patient survival is similar to that achieved by open surgery, laparoscopic liver resection has been recommended as standard care in patients undergoing left lateral segmentectomy.45,46

TABLE 2

Comparison between open and minimally invasive minor liver resections for primary liver malignancies43,44

Perioperative parameters Open surgery Laparoscopic surgery Robotic surgery
Morbidity (%) 32 16 10
Mortality (%) 0 0.3 0
R0 margins (%) 94 100 100
Operative time (minutes) 186 242 321
Estimated blood loss (ml) 903 356 306
Hospital stay (days) 10 8 7

Several studies propose that minimally invasive liver surgery is superior to open techniques because it enables a better visualization of the operating field, has a magnifying effect and is associated with reduced bleeding as a result of vein compression due to pressure exerted by the pneumoperitoneum. Furthermore it has been reported that patients can receive adjuvant chemotherapy sooner than those undergoing open liver resections.45,47 HCC has been reported to be associated with a morbidity of 20%, mortality of 0% and 1- and 5-year survival of 50% and 36%, respectively.48 The R0 resection rate varies between 90% and 100%.43,48 Laparoscopic liver surgeons need the ability to interpret sonograms as it is essential to identify vessels and bile ducts prior to surgery to determine the best dissection line. Furthermore, the resection margins of the intrahepatic lesions have to be defined to enable R0 situation. Parenchymal dissection can be carried out by different techniques using a Harmonic scalpel, LigaSure™ (Medtronic, USA), Cavitron Ultrasonic Surgical Aspirator CUSA® (Valleylab, Boulder, CO, USA) or hydrojet (Figure 5); it depends on the surgeon’s preference which instrument is used. When using the stapler during laparoscopic liver resection, higher morbidity was described.49 Operation time and blood loss is decreased when using the stapler, but the risk of bile leaks increases significantly, up to 3.4% compared with 2.2% in other dissection techniques.49

Robot-assisted liver surgery is the most innovative development in minimally invasive procedures and provides a technical add-on to conventional laparoscopy (Figure 6). Its provides more precise visualization because of its 3D view and higher magnification. The instruments have an EndoWrist (Intuitive Surgery, Sunnyvale, CO, USA), which provides more mobility at the instrument’s tip; this makes it a useful tool for vessel dissection and stitching. The surgeon can handle three instruments and a further instrument is provided via an assistant trocar. Therefore, more tools can be used simultaneously during surgery, bringing more control and safety to the operation.50 However, a comparison of laparoscopy and robot-assisted liver resection failed to identify any objective benefits of robotic techniques.43,51 Nevertheless, robot-assisted liver surgery is safe and can be used for minor and major liver resections, and is also a valuable tool for living donor hepatectomy.52 In patients with liver cirrhosis and HCC, robotic-assisted liver surgery has been described as the optimal approach as a bridge to liver transplantation53 as the liver can be handled very gently, leading to less liver trauma. This is reflected in fact that release of hepatic enzymes (aspartate transaminase and alanine transaminase) into the blood is reduced compared with open procedures.43 Another advantage is that venous shunts are respected and there is little impact on the abdominal wall. The risk of postoperative liver failure may be reduced, which should be evaluated in detail in the future.

FIGURE 6

Robot-assisted liver resection. (a) The robot is docked over the right shoulder after port placement. (b) View from the console into the operative sites; parenchyma dissection is carried out with a Harmonic scalpel. (c) Postoperative abdomen; the specimen was removed via a Pfannenstiel incision.

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Discussion

The prognosis of patients with primary liver malignancies is poor and remains an interdisciplinary challenge. Surgery plays a central role in this scenario, and for many patients an operation is the only chance of cure. This likelihood of cure can be increased by neoadjuvant or adjuvant treatment. Surgical techniques have improved dramatically over time, and more patients are suitable for tumour resection. Vessel invasion and bile duct thrombosis are no longer contraindications to surgery.12,13 Vessel reconstruction can be performed with various types of patches or biological and synthetic grafts with acceptable morbidity and mortality rates. Furthermore, bile duct reconstructions and hepaticojejunostomy to multiple bile duct ostiums are possible; however, tumours that invade vessels or bile ducts are usually progressed carcinomas, and only selected patients benefit from aggressive surgery.

One critical issue in liver surgery is the remaining liver remnant. Neoadjuvant therapies with differentiated agents damage the liver parenchyma, and most primary liver malignancies occur in pre-damaged livers with fibrosis or cirrhosis. It is essential to assess liver function of the remaining liver after surgery to prevent postoperative liver failure. Modern tests based on nuclear medicine methods or the LiMAX assay combined with imaging techniques are valuable tools to measure the functional liver capacity and to increase patient safety during surgery.26 If the liver remnant is critical, interventional techniques such as portal vein embolization or surgical methods such as ALPPS can be used to induce hypertrophy of the remaining liver.22,23 The function of these procedures has been proved and there is currently sufficient experience to implement these techniques in preoperative considerations.2123

Patients with HCCs meeting the Milan criteria and selected patients with CCs can be evaluated for liver transplantation. Molecular markers may be a tool in the future to categorize more or less aggressive tumours and to select patients for transplantation.54 The replacement of the whole liver not only removes the tumour but can reverse pre-existing liver disease. Liver transplantation is safe in experienced hands, but the lack of donor organs is an ongoing problem preventing treatment of patients within a reasonable time;31 therefore, living donor programmes should be extended in the future.

Robot-assisted liver surgery is a new tool that can be used for living donor hepatectomies.55 This provides advantages for the donors and may increase the proportion of possible living liver donors in the future. Minimally invasive procedures in liver surgery have risen dramatically and bring many benefits for patients with comparable oncological outcomes to open procedures. Gentle manipulation of the liver during these operations is of value for livers with a pre-existing impairment, which benefits from less liver damage. All types of liver resections currently described as minimally invasive procedures require surgeons with specific skills in liver surgery and specifically in minimally invasive techniques.41 However, this is the right way to improve surgical treatment for patients. Therefore, efforts and more teaching programmes in this field are necessary to train surgeons. Based on the differentiated multiple technical innovations, the surgical treatment of primary liver malignancies will become more individually tailored in the future.

References

1. 

El-Serag HB. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology 2012; 142:1264–73.e1. https://doi.org/10.1053/j.gastro.2011.12.061

2. 

Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet 2012; 379:1245–55. https://doi.org/10.1016/S0140-6736(11)61347-0

3. 

Nault JC. Pathogenesis of hepatocellular carcinoma according to aetiology. Best Pract Res Clin Gastroenterol 2014; 28:937–47. https://doi.org/10.1016/j.bpg.2014.08.006

4. 

Khan SA, Thomas HC, Davidson BR, Taylor-Robinson SD. Cholangiocarcinoma. Lancet 2005; 366:1303–14. https://doi.org/10.1016/S0140-6736(05)67530-7

5. 

Sakamoto Y, Kokudo N, Kawaguchi Y, Akita K. Clinical anatomy of the liver: review of the 19th Meeting of the Japanese Research Society of Clinical Anatomy. Liver Cancer 2017; 6:146–60. https://doi.org/10.1159/000449490

6. 

Mizuguchi T, Kawamoto M, Meguro M, et al. Prognosis and predictors of surgical complications in hepatocellular carcinoma patients with or without cirrhosis after hepatectomy. World J Surg 2013; 37:1379–87. https://doi.org/10.1007/s00268-013-1989-6

7. 

Choi SB, Kim HJ, Song TJ, et al. Influence of clinically significant portal hypertension on surgical outcomes and survival following hepatectomy for hepatocellular carcinoma: a systematic review and meta-analysis. J Hepatobiliary Pancreat Sci 2014; 21:639–47. https://doi.org/10.1002/jhbp.124

8. 

Zhou Y, Lei X, Wu L, Wu X, Xu D, Li B. Outcomes of hepatectomy for noncirrhotic hepatocellular carcinoma: a systematic review. Surg Oncol 2014; 23:236–42. https://doi.org/10.1016/j.suronc.2014.11.001

9. 

Manzini G, Henne-Bruns D, Porzsolt F, Kremer M. Is there a standard for surgical therapy of hepatocellular carcinoma in healthy and cirrhotic liver? A comparison of eight guidelines. BMJ Open Gastroenterol 2017; 4:e000129. https://doi.org/10.1136/bmjgast-2016-000129

10. 

Ryu T, Takami Y, Wada Y, et al. Double- and triple-positive tumor markers predict early recurrence and poor survival in patients with hepatocellular carcinoma within the Milan criteria and Child–Pugh class A [published online ahead of print March 15 2017]. J Gastrointest Surg 2017. https://doi.org/10.1007/s11605-017-3394-1

11. 

Wang S, Tian F, Zhao X, et al. A new surgical procedure ‘dumbbell-form resection’ for selected hilar cholangiocarcinomas with severe jaundice: comparison with hemihepatectomy. Medicine 2016; 95:e2456. https://doi.org/10.1097/MD.0000000000002456

12. 

Chen W, Ke K, Chen YL. Combined portal vein resection in the treatment of hilar cholangiocarcinoma: a systematic review and meta-analysis. Eur J Surg Oncol 2014; 40:489–95. https://doi.org/10.1016/j.ejso.2014.02.231

13. 

Groeschl RT, Nagorney DM. Portal vein reconstruction during surgery for cholangiocarcinoma. Curr Opin Gastroenterol 2016; 32:216–24. https://doi.org/10.1097/MOG.0000000000000259

14. 

Navadgi S, Chang CC, Bartlett A, McCall J, Pandanaboyana S. Systematic review and meta-analysis of outcomes after liver resection in patients with hepatocellular carcinoma (HCC) with and without bile duct thrombus. HPB 2016; 18:312–16. https://doi.org/10.1016/j.hpb.2015.12.003

15. 

Wu X, Li B, Qiu J, et al. Hepatectomy versus hepatectomy with lymphadenectomy in hepatocellular carcinoma: a prospective, randomized controlled clinical trial. J Clin Gastroenterol 2015; 49:520–8. https://doi.org/10.1097/mcg.0000000000000277

16. 

Xiaohong S, Huikai L, Feng W, Ti Z, Yunlong C, Qiang L. Clinical significance of lymph node metastasis in patients undergoing partial hepatectomy for hepatocellular carcinoma. World J Surg 2010; 34:1028–33. https://doi.org/10.1007/s00268-010-0400-0

17. 

Yamamoto M, Takasaki K, Yoshikawa T. Lymph node metastasis in intrahepatic cholangiocarcinoma. Jpn J Clin Oncol 1999; 29:147–50. https://doi.org/10.1093/jjco/29.3.147

18. 

Chang ME, Lei HJ, Chen MH, et al. Evaluation of prognostic factors and implication of lymph node dissection in intrahepatic cholangiocarcinoma: 10-year experience at a tertiary referral center. J Chin Med Assoc 2017; 80:140–6. https://doi.org/10.1016/j.jcma.2016.09.010

19. 

Choi SB, Kim KS, Choi JY, et al. The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival. Ann Surg Oncol 2009; 16:3048–56. https://doi.org/10.1245/s10434-009-0631-1

20. 

Delis SG, Dervenis C. Selection criteria for liver resection in patients with hepatocellular carcinoma and chronic liver disease. World J Gastroenterol 2008; 14:3452–60. https://doi.org/10.3748/wjg.14.3452

21. 

Glantzounis GK, Tokidis E, Basourakos SP, Ntzani EE, Lianos GD, Pentheroudakis G. The role of portal vein embolization in the surgical management of primary hepatobiliary cancers. A systematic review. Eur J Surg Oncol 2017; 43:32–41. https://doi.org/10.1016/j.ejso.2016.05.026

22. 

Malinowski M, Geisel D, Stary V, et al. Portal vein embolization with plug/coils improves hepatectomy outcome. J Surg Res 2015; 194:202–11. https://doi.org/10.1016/j.jss.2014.10.028

23. 

Vivarelli M, Vincenzi P, Montalti R, et al. ALPPS procedure for extended liver resections: a single centre experience and a systematic review. PLOS ONE 2015; 10:e0144019. https://doi.org/10.1371/journal.pone.0144019

24. 

Cieslak KP, et al. Future remnant liver function as predictive factor for the hypertrophy response after portal vein embolization [published online ahead of print March 29 2017]. Surgery 2017. https://doi.org/10.1016/j.surg.2016.12.031

25. 

Aoki T, Kubota K. Preoperative portal vein embolization for hepatocellular carcinoma: consensus and controversy. World J Hepatol 2016; 8:439–45. https://doi.org/10.4254/wjh.v8.i9.439

26. 

Stockmann M, Lock JF, Malinowski M, Niehues SM, Seehofer D, Neuhaus P. The LiMAx test: a new liver function test for predicting postoperative outcome in liver surgery. HPB 2010; 12:139–46. https://doi.org/10.1111/j.1477-2574.2009.00151.x

27. 

Conrad C, Shivathirthan N, Camerlo A, Strauss C, Gayet B. Laparoscopic portal vein ligation with in situ liver split for failed portal vein embolization. Ann Surg 2012; 256:e14–15. https://doi.org/10.1097/SLA.0b013e318265ff44

28. 

Pandanaboyana S, Bell R, Hidalgo E, et al. A systematic review and meta-analysis of portal vein ligation versus portal vein embolization for elective liver resection. Surgery 2015; 157:690–8. https://doi.org/10.1016/j.surg.2014.12.009

29. 

Schadde E, Schnitzbauer AA, Tschuor C, Raptis DA, Bechstein WO, Clavien PA. Systematic review and meta-analysis of feasibility, safety, and efficacy of a novel procedure: associating liver partition and portal vein ligation for staged hepatectomy. Ann Surg Oncol 2015; 22:3109–20. https://doi.org/10.1245/s10434-014-4213-5

30. 

Parikh ND, Yopp A, Singal AG. Controversies in criteria for liver transplantation in hepatocellular carcinoma. Curr Opin Gastroenterol 2016; 32:182–8. https://doi.org/10.1097/MOG.0000000000000264

31. 

Menahem B, Lubrano J, Duvoux C, et al. Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: attempt to perform an ideal meta-analysis [published online ahead of print March 14 2017]. Liver Transpl 2017. https://doi.org/10.1002/lt.24758

32. 

Proneth A, Zeman F, Schlitt HJ, Schnitzbauer AA. Is resection or transplantation the ideal treatment in patients with hepatocellular carcinoma in cirrhosis if both are possible? A systematic review and metaanalysis. Ann Surg Oncol 2014; 21:3096–107. https://doi.org/10.1245/s10434-014-3808-1

33. 

Feng J, Zhu R, Chang C, et al. CK19 and Glypican 3 expression profiling in the prognostic indication for patients with HCC after surgical resection. PLOS ONE 2016; 11:e0151501. https://doi.org/10.1371/journal.pone.0151501

34. 

Hong SK, Lee KW, Kim HS, Yoon KC, Yi NJ, Suh KS. Living donor liver transplantation for hepatocellular carcinoma in Seoul National University. Hepatobiliary Surg Nutr 2016; 5:453–60. https://doi.org/10.21037/hbsn.2016.08.07

35. 

Hong G, Suh KS, Suh SW, Yoo T, Kim H, Park MS. Alpha-fetoprotein and 18F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation. J Hepatol 2016; 64:852–9. https://doi.org/10.1016/j.jhep.2015.11.033

36. 

Magistri P, Tarantino G, Serra V, Guidetti C, Ballarin R, Di Benedetto F. Liver transplantation and combined hepatocellular-cholangiocarcinoma: feasibility and outcomes. Dig Liver Dis 2017. https://doi.org/10.1016/j.dld.2017.01.166

37. 

Gupta R, Togashi J, Akamatsu N, Sakamoto Y, Kokudo N. Impact of incidental/misdiagnosed intrahepatic cholangiocarcinoma and combined hepatocellular cholangiocarcinoma on the outcomes of liver transplantation: an institutional case series and literature review [published online ahead of print January 25 2017]. Surg Today 2017. https://doi.org/10.1007/s00595-017-1472-3

38. 

Mantel HT, Westerkamp AC, Adam R, et al. Strict selection alone of patients undergoing liver transplantation for hilar cholangiocarcinoma is associated with improved survival. PLOS ONE 2016; 11:e0156127. https://doi.org/10.1371/journal.pone.0156127

39. 

Rosen CB, Heimbach JK, Gores GJ. Surgery for cholangiocarcinoma: the role of liver transplantation. HPB 2008; 10:186–9. https://doi.org/10.1080/13651820801992542

40. 

Conrad C, Ogiso S, Inoue Y, Shivathirthan N, Gayet B. Laparoscopic parenchymal-sparing liver resection of lesions in the central segments: feasible, safe, and effective. Surg Endosc 2015; 29:2410–17. https://doi.org/10.1007/s00464-014-3924-9

41. 

Ishizawa T, Gumbs AA, Kokudo N, Gayet B. Laparoscopic segmentectomy of the liver: from segment I to VIII. Ann Surg 2012; 256:959–64. https://doi.org/10.1097/SLA.0b013e31825ffed3

42. 

Lainas P, Camerlo A, Conrad C, Shivathirthan N, Fuks D, Gayet B. Laparoscopic right hepatectomy combined with partial diaphragmatic resection for colorectal liver metastases: Is it feasible and reasonable? Surgery 2015; 158:128–34. https://doi.org/10.1016/j.surg.2015.02.003

43. 

Croner RS, Perrakis A, Hohenberger W, Brunner M. Robotic liver surgery for minor hepatic resections: a comparison with laparoscopic and open standard procedures. Langenbecks Arch Surg 2016; 401:707–14. https://doi.org/10.1007/s00423-016-1440-1

44. 

Nguyen KT, Gamblin TC, Geller DA. World review of laparoscopic liver resection-2,804 patients. Ann Surg 2009; 250:831–41. https://doi.org/10.1097/SLA.0b013e3181b0c4df

45. 

Wakabayashi G, Cherqui D, Geller DA, et al. Recommendations for laparoscopic liver resection: a report from the second international consensus conference held in Morioka. Ann Surg 2015; 261:619–29. https://doi.org/10.1097/SLA.0000000000001184

46. 

Wakabayashi G, Cherqui D, Geller DA, et al. Laparoscopic hepatectomy is theoretically better than open hepatectomy: preparing for the 2nd International Consensus Conference on Laparoscopic Liver Resection. J Hepatobiliary Pancreat Sci 2014; 21:723–31. https://doi.org/10.1002/jhbp.139

47. 

Yan Y, Cai X, Geller DA. Laparoscopic liver resection: a review of current status [published online ahead of print May 21 2017]. J Laparoendosc Adv Surg Tech A 2017. https://doi.org/10.1089/lap.2016.0620

48. 

Geller DA, Tsung A. Long-term outcomes and safety of laparoscopic liver resection surgery for hepatocellular carcinoma and metastatic colorectal cancer. J Hepatobiliary Pancreat Sci 2015; 22:728–30. https://doi.org/10.1002/jhbp.278

49. 

Buell JF, Gayet B, Han HS, et al. Evaluation of stapler hepatectomy during a laparoscopic liver resection. HPB 2013; 15:845–50. https://doi.org/10.1111/hpb.12043

50. 

Croner R, Perrakis A, Grützmann R, Hohenberger W, Brunner M. [Robotic-assisted liver surgery.] Zentralbl Chir 2016; 141:154–9. https://doi.org/10.1055/s-0042-104067

51. 

Packiam V, Bartlett DL, Tohme S, et al. Minimally invasive liver resection: robotic versus laparoscopic left lateral sectionectomy. J Gastrointest Surg 2012; 16:2233–8. https://doi.org/10.1007/s11605-012-2040-1

52. 

Chen PD, Wu YM. Re: Living donor liver transplantation: are we ready for full robotic harvesting? [published online ahead of print April 13 2017]. Liver Transpl 2017. https://doi.org/10.1002/lt.24771

53. 

Magistri P, Tarantino G, Ballarin R, Coratti A, Di Benedetto F. Robotic liver surgery is the optimal approach as bridge to transplantation. World J Hepatol 2017; 9:224–6. https://doi.org/10.4254/wjh.v9.i4.224

54. 

Forner A, Bruix J. Biomarkers for early diagnosis of hepatocellular carcinoma. Lancet Oncol 2012; 13:750–1. https://doi.org/10.1016/S1470-2045(12)70271-1

55. 

Magistri P, Tarantino G, Ballarin R, et al. Living donor liver transplantation: are we ready for full robotic harvesting? [published online ahead of print April 13 2017]. Liver Transpl 2017. https://doi.org/10.1002/lt.24767


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