Malignant liver tumours

The liver is commonly affected by malignant tumours, both primary and secondary. The majority of liver tumours are diagnosed radiologically, and MRI and CT are accurate at detecting even small tumours. Hepatocellular carcinoma (HCC) is the most common primary tumour and often presents on a background of liver cirrhosis. The curative options for HCC are liver resection and transplantation. However, non-curative management such as radiofrequency ablation and transarterial chemoembolisation (TACE) can prolong survival in patients not suited to curative management. Cholangiocarcinoma is a less common malignancy but unfortunately has poorer outcomes. It affects the bile ducts and treatment relies on resection of the affected liver and biliary tree, requiring reconstruction of the biliary drainage system. Postoperative morbidity is high and long-term survival is often short. Colorectal liver metastases are the most common liver tumours. With improvements in preoperative chemotherapy and surgical techniques such as portal vein embolization (PVE) and two stage resections, curative resection with good long-term outcomes are often achieved.     

Malignant tumours of the liver

Malignant tumours of the liver can either be primary (arising from the liver) or secondary (metastasis from a distant primary tumour). Clinical symptoms are non-specific and tumours are diagnosed incidentally or during surveillance imaging. Contrast-enhanced CT and MRI with hepatobiliary contrast are both excellent imaging modalities used for evaluation of these tumours. Hepatocellular carcinoma (HCC) is the most common primary tumour and often presents on a background of liver cirrhosis. Tumour size, degree of liver cirrhosis and patient performance status dictate management pathways. Surgical resection, ablation and liver transplantation are curative options in selected patients. However, noncurative management such as transarterial chemoembolization (TACE) can prolong survival in patients not suited to curative management. Cholangiocarcinoma is a less common malignancy of the biliary epithelium but unfortunately has poorer outcomes. Extended liver resections with biliary reconstructions are usually required for cure but postoperative morbidity is high and long-term survival is often short. Colorectal liver metastases are the most common liver tumours. Curative resection with good long-term outcomes are often achieved with improvements in preoperative chemotherapy, surgical techniques, newer radiological interventions such as portal vein embolization (PVE) and two-stage resections. The role of liver transplantation in management of malignant liver tumours is promising and under investigation.     

Malignant liver tumours

The liver is commonly affected by both primary and metastatic malignancy. The surgical management of liver tumours must be carefully considered to ensure good oncological outcomes and to avoid serious complications of liver surgery. Primary tumours of the liver include hepatocellular carcinoma and cholangiocarcinoma. The resectability of primary liver tumours is dependent on thorough preoperative staging. Primary liver tumours pose a major global health burden, particularly in Asia and in countries affected by epidemic viral hepatitis. Metastatic disease commonly affects the liver and often hepatic resection in such circumstances provides the best chance of prolonging life and disease free survival. This review discusses recent advances, in addition to the epidemiology, diagnosis and management of both primary and secondary liver tumours.     

Malignant liver tumours

Malignant liver tumours can be primary or secondary. The most common primary malignant liver tumours are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC), while the colorectal and neuroendocrine liver metastases account for the majority of secondary tumours.HCC tends to arise in patients with cirrhosis secondary to hepatitis or alcohol. Diagnosis is usually made on a raised α-fetoprotein and CT and MRI. Treatment options include hepatic resection, transplantation, percutaneous ablation and transarterial chemo-embolization. Treatment is dependent on the Child’s status of the patient, extent of liver disease and the presence of metastatic disease.IHC accounts for 10% of cholangiocarcinomas. Risk factors include primary sclerosing cholangitis and choledochal cysts. Liver resection offers the only chance for cure in these patients.Secondary liver tumours account for 95% of hepatic malignancies, the most common being colorectal liver metastases (CRLM). CRLM are detected during surveillance following surgery for the primary tumour. Liver resection is potentially curative, and more patients are being subjected to liver resection following down-staging of the disease with neoadjuvant chemotherapy.Surgery offers a potential cure for liver tumours. Recent medical advances have made treatment of malignant liver tumours safer and potentially curative.     

Surgical treatment for recurrent hepatocellular carcinoma: Current status and challenges

Primary liver cancer is the sixth most commonly diagnosed cancer and was the third leading cause of cancer deaths worldwide in 2020. It includes hepatocellular carcinoma (HCC) (representing 75%-85% of cases), intrahepatic cholangiocarcinoma (representing 10%-15% of cases), and other rare types. The survival rate of patients with HCC has risen with improved surgical technology and perioperative management in recent years; however, high tumor recurrence rates continue to limit long-term survival, even after radical surgical resection (exceeding 50% recurrence). For resectable recurrent liver cancer, surgical removal [either salvage liver transplantation (SLT) or repeat hepatic resection] remains the most effective therapy that is potentially curative for recurrent HCC. Thus, here, we introduce surgical treatment for recurrent HCC. Areas Covered: A literature search was performed for recurrent HCC using Medline and PubMed up to August 2022. Expert commentary: In general, long-term survival after the re-resection of recurrent liver cancer is usually beneficial. SLT has equivalent outcomes to primary liver transplantation for unresectable recurrent illness in a selected group of patients; however, SLT is constrained by the supply of liver grafts. SLT seems to be inferior to repeat liver resection when considering operative and postoperative results but has the major advantage of disease-free survival. When considering the similar overall survival rate and the current situation of donor shortages, repeat liver resection remains an important option for recurrent HCC.     

Debate: Resection for Early Hepatocellular Carcinoma

The management of patients with cirrhosis and early hepatocellular carcinoma (HCC) meeting the Milan criteria is controversial. Although liver transplantation for early HCC has been shown to have excellent long term survival rates and low recurrence rates, its application is limited by organ availability. Hepatic resection is an alternative therapy for early HCC. Hepatic resection can be performed safely in patients with early HCC and well-compensated cirrhosis. In addition, the reported 5-year survival rates are in the range of 50%. Resection may also allow a better understanding of tumor biology through pathologic examination of the specimen while also providing a potentially curative therapeutic option. The management of patients with early HCC is complex. Resection should not be viewed as opposing transplantation. Rather, hepatic resection should be seen as complementary to transplantation. The best therapeutic strategies for patients with early HCC and well-compensated cirrhosis should be dependent on the individual clinical situation, not adherence to dogmatic universal adoption of either resection or transplantation.     

Repeat Liver Resection for Hepatocellular Carcinoma Complicating Primary Biliary Cirrhosis

The incidence of hepatocellular carcinoma (HCC) complicating primary biliary cirrhosis (PBC) is between 0.7% and 16%. Repeat liver resection for recurrent HCC complicating PBC is not usually performed and not published because this approach is not generally applicable due to liver dysfunction. We applied repeat liver resection for these diseases. Three patients were diagnosed with PBC. The first HCC was noted at a mean of 6 years (4–17 years) after diagnosis of PBC. The second HCC occurred at a mean of 2.5 years (0.4–3 years) after the first surgery. All patients were treated with curative resection on first and second surgery. The mean overall survival time after the first liver resection was 46 months. Repeat liver resection for recurrent HCC complicating PBC is an option and may improve the outcome.     

Liver resection for hepatocellular carcinoma in patients without cirrhosis

Background:

Data on liver resection for hepatocellular carcinoma (HCC) without cirrhosis are sparse. The present study was conducted to evaluate the indications and results of liver resection for HCC with regard to safety and efficacy.

Methods:

Data for patients who had liver resection for HCC without cirrhosis between January 1996 and March 2011 were retrieved retrospectively using a prospective database containing information on all patients who underwent hepatectomy for HCC. Patient and tumour characteristics were analysed for influence on overall and disease‐free survival to identify prognostic factors by univariable and multivariable analysis.

Results:

The 1‐, 3‐ and 5‐year overall survival rates after resection with curative intent for HCC without cirrhosis were 84, 66 and 50 per cent respectively. Disease‐free survival rates were 69, 53 and 42 per cent respectively. The 90‐day mortality rate was 4·5 per cent (5 of 110 patients). Surgical radicality and growth pattern of the tumour were independent prognostic factors for overall survival. Disease‐free survival after resection with curative intent was independently affected by growth pattern and by the number and size of tumour nodules.

Conclusion:

Liver resection for HCC without cirrhosis carries a low perioperative risk and excellent long‐term outcome if radical resection is achieved. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Liver transplantation for primary and metastatic liver cancers

Liver transplantation for hepatic malignancies has emerged as a well‐documented and proven treatment modality. However, early unsatisfactory results emphasized that only a highly selected patient population would benefit from transplantation. Currently, 15% of all liver transplants performed are for hepatocellular carcinoma (HCC). There is no controversy about the fact that liver transplantation for HCC in the adult population yields good results for patients whose tumour masses do not exceed the Milan criteria. It remains to be determined whether patients with more extensive tumours can be reliably selected to benefit from the procedure. In patients with small HCC at an early stage and preserved liver function, liver resection provides an alternative to transplant. Liver resection may offer similar survival results to orthotopic liver transplantation (OLT) in the short term, and does not carry the long‐term effects of immunosuppression; however, long‐term and disease‐free survival favours liver transplantation. Very promising results have been obtained for cholangiocarcinoma treated by aggressive combination therapies, including chemo‐ and radiotherapy followed by OLT. Survival rate in these selected patients can approach that of patients with cholestatic liver disease, and the role of transplantation now requires re‐evaluation. Similarly, hepatoblastoma is an excellent indication in paediatric patients with unresectable or recurrent tumours. Epithelioid hemangioendothelioma is also an appropriate indication for liver transplantation, even in the presence of extrahepatic metastases, unlike angiosarcoma which is associated with a very poor survival and considered as a contraindication. And finally for metastatic liver disease from neuroendocrine tumours, liver transplantation can result in long‐term survival and even cure in well selected patients. Conversely, the value of transplantation for colorectal liver metastases (currently a contraindication) requires further evaluation by well‐designed trials.     

Treatment Options and Surveillance Strategies After Therapy for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and the third leading cause of cancer death worldwide. Recurrence rates after curative intent treatment for HCC are high; 5-year disease-free survival ranges from only 19 to 81 %. There is no direct evidence to guide the optimal frequency and method of surveillance for recurrent HCC after curative intent treatment. In contrast, there is strong evidence supporting both primary screening for HCC in patients with chronic liver disease. After resection, HCC tends to recur locally, whereas the pattern after transplantation is more at extrahepatic sites. In theory, if an HCC recurrence is discovered early, more therapeutic options are available for treatment of the recurrent HCC. As such, close surveillance after curative intent therapy may have the potential to prolong survival. We herein review the available literature derived from primary surveillance of patients with cirrhosis, as well as data on postoperative surveillance of HCC patients. In aggregate, although data remain scarce, close surveillance with α-fetoprotein and cross-sectional imaging every 3–4 months for 3 years after curative intent therapy, followed by surveillance every 6–12 months thereafter, seems the most prudent approach to follow-up of patients with HCC in the postsurgical setting.     

Re-evaluation of lipiodolized transarterial chemoembolization therapy for intrahepatic recurrence of hepatocellular carcinoma after curative liver resection

Background/Purpose  While lipiodolized transarterial chemoembolization (lip-TACE) is effective for treating unresectable hepatocellular carcinoma (HCC), its effect for treating recurrent HCC after curative liver resection needs to be clarified. Methods  Of 163 patients who had undergone curative liver resection between 1992 and December 2003, 65 patients (39.8%) had recurrent HCC in the liver without extrahepatic recurrence and were indicated for lip-TACE. The overall survival rate after lip-TACE was calculated, and its correlation with factors such as the histology of the primary HCC and background noncancerous tissue were analyzed. Results  The overall survival rates after lip-TACE after the detection of the first recurrent HCC were 82.6%, 44.5%, and 24.8% at 1, 3, and 5 years, respectively. The factors affecting patient survival after lip-TACE were microscopic portal venous involvement of HCC at liver resection, grade of inflammation in the noncancerous liver parenchyma, and recurrence within 1 year after the initial liver resection. Multivariate analysis showed that the period between the resection and first recurrence had the highest hazard ratio. Conclusions  Lip-TACE is a reasonable procedure for treating recurrent HCC in selected patients who are not eligible for hepatic re-resection. When HCC recurred within 1 year from the primary liver resection, the effect of lip-TACE on patient survival was limited.     

Hepatocellular carcinoma presenting with obstructive jaundice

BACKGROUND: Jaundice occurs in 5-44% of patients with hepatocellular carcinoma (HCC). It is an important clinical presentation as the different aetiological causes of jaundice in HCC determine the therapeutic approach and the prognosis. This article aims to review the classification, management and prognosis of patients with jaundice associated with HCC. METHODS: A Medline search was undertaken to identify articles using the key words 'hepatocellular carcinoma', 'jaundice' and 'tumour thrombus'. Additional articles were identified by a manual search of the references from the key articles. RESULTS: Patients with jaundice due to hepatic parenchymal insufficiency (hepatocellular type) have a very dismal prognosis. For patients with biliary obstruction due to HCC (icteric type), the reported 1-, 3- and 5-year survival rates after curative resection were 57.1-100%, 20-47% and 6.7-45%, respectively. The mean survival after palliative biliary drainage alone was less than 6 months but when biliary drainage was combined with other palliative treatment, the mean survival could be up to 1 year. CONCLUSIONS: It is important to differentiate the hepatocellular type from the icteric type of HCC. For patients with the icteric type of HCC, curative liver resection can achieve a survival comparable to that in patients without jaundice. For patients with unresectable icteric type of HCC, treatment can provide improvement in patient's quality of life and survival.     

The benefit of curative liver resection with a selective bile duct preserving approach for hepatocellular carcinoma with macroscopic bile duct tumor thrombus

BackgroundHepatocellular carcinoma (HCC) presenting with macroscopic bile duct tumor thrombus (BDTT) is an uncommon event. The role of a curative hepatic resection and associated long-term outcomes remain controversial. In addition the necessity for bile duct resection is still unclear. The aim of this study was to evaluate outcomes of hepatectomy with a selective bile duct preservation approach for HCC with BDTT in comparison to outcomes without BDTT.MethodsA total of 22 HCC with BDTT patients who had undergone curative hepatic resection with a selective bile duct preservation approach at our institute were retrospectively reviewed. These were compared to group of 145 HCC without BDTT patients. The impact of curative surgical resection and BDTT on clinical outcomes and survival after surgical resection were analyzed.ResultsAll HCC with BDTT cases underwent major hepatectomy vs. 32.4% in the comparative group. Bile duct preservation rate was 56.5%. The 1-, 3- and 5-year survival rates of HCC with BDTT patients in comparison to the HCC without BDTT group were 81.8%, 52.8% and 52.8% vs. 73.6%, 55.6% and 40.7% (P=0.804) respectively. Positive resection margin, tumor size ≥5 cm and AFP ≥200 IU/mL were significant risk factors regarding overall survival. However, it is unclear whether presence of a bile duct tumor thrombus has an adverse impact on either recurrence free survival or overall survival.ConclusionsBile duct obstruction from tumor thrombus did not necessarily indicate an advanced form of disease. Tumor size and AFP had greater impact on long-term outcomes than bile duct tumor thrombus. Major liver resection with a selective bile duct preserving approach in HCC with BDTT can achieve favorable outcomes comparable to those of HCC without BDTT in selected patients.     

Alcoholic liver cirrhosis. Treatment of hepatocellular carcinoma

TRANSPLANTATION AND RESECTION: Surgery is still the only curative treatment of hepatocellular carcinoma (HCC). For patients with cirrhosis, liver transplantation for HCC with one nodule less than 5 cm in diameter, or no more than three nodules each less than 3 cm, gives the best results with a 5-year survival rate of 70%. Resection of a single tumor for patients with good liver function may also be performed with curative intent but the rate of recurrence is high. OTHER TECHNIQUES: Cryotherapy and radiofrequency are in-situ destruction methods used for small tumors. In the future, these procedures may compete with hepatic resection. When used alone, intra-arterial treatments, such as chemoembolisation, have only a palliative intent, but they also may be combined with other procedures. The treatment of advanced HCC is still limited and there is no standard approach for its management. HCC WITHOUT CIRRHOSIS: For those with HCC without cirrhosis, the same treatments are available but resection is more often performed because of the ability of the liver to regenerate. The management of patients with HCC with or without cirrhosis may combine several treatment modalities and needs a multi-disciplinary approach.     

Current status of surgical management of patients with gastroenteropancreatic neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) of the gastroenteropancreatic system are rare and heterogeneous tumours, yet with increasing prevalence. The most frequent primary sites are the small intestine, rectum, pancreas, and stomach. For a localized disease, surgical resection with local lymph nodes is usually curative with good overall and disease free survival. More complex situation is the treatment of locally advanced lesions, liver metastases, and, surprisingly, small asymptomatic tumours of the rectum and pancreas. In this review, we focus on the current role of surgical management of gastroenteropancreatic NENs. We present surgical approach for the most frequent primary sites. We highlight the role of endoscopic surgery and the watch-and-wait strategy for selected cases. As liver metastases pose an important clinical challenge, we present current indications and contraindications for liver resection and a role of liver transplantation for metastatic NENs.     

Long-term survival outcome of laparoscopic liver resection for hepatocellular carcinoma

Long-term survival is the most important outcome measurement of a curative oncological treatment. For hepatocellular carcinoma (HCC), the long-term disease-free and overall survival of laparoscopic liver resection (LLR) is shown to be non-inferior to the current standard of open liver resection (OLR). Some studies have reported a superior long-term oncological outcome in LLR when compared to OLR. It has been argued that improvement of visualization and instrumentation and reduced operative blood loss and perioperative blood transfusion may contribute to reduced risk of postoperative tumor recurrence. On the other hand, since most of the comparative studies of the oncological outcomes of LLR and OLR for HCC are non-randomized, it remained inconclusive as to whether LLR confers additional survival benefit compared to OLR. Despite the paucity of level 1 evidence, the practice of LLR for HCC has gained wide-spread acceptance due to the reproducible improvements in the perioperative outcomes and non-inferior oncological outcomes demonstrated by large-scaled, matched comparative studies. Meta-analyses of the outcomes of these studies by multiple systematic reviews have also returned noncontradictory conclusions. On the basis of a theoretical advantage of LLR over OLR in preventing tumor recurrence, the current review aims to dissect from the current meta-analyses and comparative studies any evidence of such superiority.     

Chinese experience with hepatectomy for huge hepatocellular carcinoma

BACKGROUND: The risks and outcome of hepatic resection for huge hepatocellular carcinoma (HCC) are controversial. METHODS: The clinical records of 525 patients who underwent resection of HCC greater than 10 cm in diameter were studied retrospectively. Prognostic factors for long-term survival were evaluated by univariate and multivariate analyses. RESULTS: Postoperative complications were common (26.8 per cent) and five patients (0.9 per cent) required relaparotomy. The 30-day mortality rate was 2.7 per cent. The main causes of postoperative death were liver failure (nine patients) and bleeding (four). The 3-, 5- and 10-year crude survival rates after liver resection were 34.3, 16.8 and 2.9 per cent respectively. CONCLUSION: Prognostic factors for long-term survival mainly reflected the biological behaviour of the tumour. They can be used only as a guide in balancing the risks of operation against the potential benefits of resection in a patient in poor general condition or with poor liver function. They cannot be used alone to exclude patients from liver resection with curative intent. Liver resection for huge HCC was safe and efficacious. It should be used to treat patients with acceptable surgical risks and resectable tumours.     

肝癌的综合治疗

Hepatocellular carcinoma(HCC)is nowadays one of the leading common causes of cancer death and mostly occurs in hepatitis B endemic areas.Typically,HCC patients presented late and only about 20% of the patients are amendable to surgical interventions.Surgical resection is the main curative treatment option.Nevertheless,the recurrence rate after potential curative liver resection is still very high.On the other hand,liver transplantation is the treatment of choice for early small HCC but its application is limited by the availability of liver grafts.Radiofrequency ablation is more commonly used in cirrhotic patients with small tumours who are not surgical candidates.Nowadays,transarterial chemoembolisation,drugeluting bead transarterial chemoembolisation and radioembolisation are the mainstay of treatments for the patients with intermediate HCC.Other systemic approaches,such as hormonal therapy,immunotherapy and chemotherapy have disappointing results.In particular,HCC is highly refractory to cytotoxic chemotherapy.This is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients.Recently,encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients.Similar to sorafenib,other anti-angiogenic multi-targeted tyrosine kinase inhibitors,such as pazopanib,brivanib and axitinib also show promising activity in various stages of clinical trials.There is an urgent need to identify biomarkers that may guide the rational use of sorafenib and other targeted agents in the era of personalised medicine.More importantly,the multidisciplinary model in managing HCC patients is the important key to the future success.     

Interstitial laser thermotherapy for liver tumours

BACKGROUND: Primary hepatocellular carcinoma (HCC) and metastases from colorectal cancer are the most common malignant liver tumours. Surgical resection is the optimum treatment in suitable patients. Interstitial laser thermotherapy (ILT) is gaining acceptance for the treatment of irresectable liver tumours and as a potential alternative to surgery. An understanding of the principles of therapy and review of clinical outcomes may allow better use of this technology. METHOD: An electronic search using the Medline database was performed for studies on the treatment of hepatic malignancy published between January 1983 and February 2003. RESULTS: Current information on the efficacy of ILT is based on prospective studies. ILT appears to be a safe and minimally invasive technique that consistently achieves tumour destruction. The extent of destruction depends on the fibre design, delivery system, tumour size and tumour biology. Real-time magnetic resonance imaging provides the most accurate assessment of laser-induced tumour necrosis. In selected patients with HCC and colorectal cancer liver metastases, ILT achieves complete tumour necrosis, provides long-term local control, and improves survival, compared with the natural history of the disease. In addition, ILT has survival benefits for patients with other tumour types, especially those with isolated liver metastases from a breast cancer primary. CONCLUSION: ILT improves overall survival in specific patients with liver tumours. Advances in laser technology and refinements in technique, and a better understanding of the processes involved in laser-induced tissue injury, may allow ILT to replace surgery as the procedure of choice in selected patients with liver malignancies.     

Perihilar cholangiocarcinoma: What the radiologist needs to know

Perihilar cholangiocarcinoma (PHC) is a common and highly intractable malignancy of the main biliary tree confluence. PHC is associated with a poor prognosis because of its insidious local spread that makes it challenging to diagnose and assess. Surgical resection remains the standard curative treatment (up to 50% 5-year overall survival after negative-margin resection). More aggressive surgical approaches have recently emerged, pushing the boundaries of PHC resectability at the cost of a higher morbidity. As such, adequate preoperative preparation (i.e., biliary drainage, venous embolization) is now regarded as a critical issue to increase the number of patients amenable to extended liver resection. Thorough imaging plays a pivotal role in the preoperative setting in both PHC resectability assessment and patient preparation to surgery. Despite recent improvement in PHC imaging, its assessment remains challenging and only 50–60% of patients who are scheduled to undergo surgery are ultimately amenable to curative resection. Therefore, a knowledge of available diagnostic and interventional imaging techniques is important to improve PHC management. Herein, we review the various imaging techniques and preoperative radiological interventions such as biliary drainage, portal vein embolization and liver venous deprivation that are available in PHC management focusing on the anatomical and oncological considerations that are crucial to prepare and guide curative surgical resection.