Early Stage Hepatocellular Carcinoma Detected during Intraoperative Ultrasonography

Objectives: Recently, it has been recognized that there are increasing incidences of hepatocellular carcinoma (HCC) multicentricity. Thus, intraoperatively detected hepatic lesions that were once thought to be metastatic lesions now need to be carefully reexamined to determine whether they are true metastatic lesions or the multicentric development of HCC. Methods: We investigated the histological characteristics of small nodular lesions detected during intraoperative ultrasonography in 33 consecutive patients with small HCC wbo underwent laparotomy at our institution. Results: Fourteen nodular lesions were found incidentally in 10 of 33 patients (30.3%), and were classified into tbe following three groups: 11 nodules in nine patients (27.3%) were HCC, two nodules in two patients (6.1%) were hemangioma, and one nodule in one patient (3.0%) was a large regenerative nodule. HCC therefore comprised 78.6% of tbe intraoperatively detected nodular lesions. Of the 11 HCCs, six were hyperechoic, four were hypoechoic, and one was isoechoic. Five (83.3%) of six small hyperechoic HCCs and two (50.0%) of four hypoechoic HCCs were well differentiated and retained their preexisting liver structure. Tbese findings closely coincide with the characteristics of early stage HCC. Thus, early stage HCC comprised 63.6% of tbe intraoperatively detected HCC cases. Conclusions: A certain proportion of small satellite HCCs detected during intraoperative ultrasonography in patients with small HCC, which were previously thought to be metastatic lesions from tbe main HCC, may instead he early stage HCCs. Such findings would also support the concept of the multicentric development of HCC. Approximately 60% of all small HCC cases detected intraoperatively may be early stage HCC. As a result, it is predicted that the emergence of HCC is either multicentric or unicentric, with early intrabepatic spread, altbough the former seems to be more common.     

Das hepatozellul?re Karzinom aus der Sicht des Internisten und des Chirurgen

Hepatocellular carcinoma (HCC) is the 5th most common cancer in the world and the 3rd cause of cancer-related death. Despite therapeutic advances, the overall survival of patients with HCC has not significantly improved in the last decades. Because in the majority of patients HCCs develop in a cirrhotic liver, the patient’s prognosis depends not only on the tumor stage but also on the liver function. Patients at an early stage with an asymptomatic single HCC with a maximum diameter of 5 cm or up to three nodules each less than 3 cm may benefit from curative therapies, including resection, liver transplantation, and percutaneous ablation. Patients exceeding these limits, but who are free of cancer-related symptoms and vascular invasion or extrahepatic spread, may benefit from palliation with chemoembolization. The advanced stage is characterized by mild cancer-related symptoms and/or vascular invasion or extrahepatic spread. Patients at this stage are eligible for treatment with sorafenib; however, a variety of other new drugs, including small molecules and antibodies, are being tested in randomized controlled trials. The development and evaluation of novel HCC treatment strategies as well as the implementation of existing measures and the development of new ones to prevent HCCs are of utmost importance. A better understanding of the clinical and molecular pathogenesis of HCCs should lead to improved diagnostic, therapeutic, and preventive strategies, with the aim to reduce the incidence of HCC, one of the most devastating malignancies worldwide.     

Histopathology of liver cancers

Recently, new pathomorphologic information about early-stage small hepatocellular carcinoma (HCC) and the multi-step process of human hepatocarcinogenesis has been obtained, along with advances in the development of diagnostic modalities. The most valuable information is that in the majority of cases HCC arises as a very well differentiated cancer and proliferates with a stepwise process of dedifferentiation. In addition, it has been suggested that many HCCs seem to arise from dysplastic nodules (DNs) on the basis of the following evidence: the presence of DNs containing HCC foci, frequent association of DNs in the vicinity of HCC, and clinical progression from DN to HCC. However, as many HCCs are still detected at an advanced stage, it is also important to understand not only the classical pathologic features of HCC but also unusual features such as scirrhous change, sarcomatous change, fibrolamellar variant, and intra-bile duct or intra-atrial tumor growth.     

Clinical value of gadoxetic acid-enhanced magnetic resonance imaging in surgery for hepatocellular carcinoma - with a special emphasis on early hepatocellular carcinoma

Gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) achieves excellent lesion detection and characterization for both hypervascular hepatocellular carcinoma (HCC) in arterial phase imaging and hypovascular early HCC (small well-differentiated HCC of the vaguely nodular type) in hepatobiliary phase imaging, and has become an indispensable imaging modality in the treatment of HCC. Early HCCs have been detected more frequently since the introduction of EOB-MRI into daily clinical practice. Early HCC is known to progress to conventional hypervascular HCC, and many risk factors have been identified for the hypervascularization of early HCC including the diameter of the tumor, presence of fat, and imaging findings of EOB-MRI. The rate of the development of hypervascular HCC was previously reported to be high in patients with chronic liver disease and early HCC. The presence of early HCC is regarded as a predictor for the recurrence of HCC following hepatic resection. On the other hand, although early HCC itself is currently not regarded as a target lesion for hepatic resection, early HCC at high risk of hypervascularity needs to be treated by local ablation therapy. If concomitant early HCC with progressed HCC is at high risk of hypervascularization and the functional liver reserve of a patient is sufficient, its simultaneous treatment at the time of hepatic resection for progressed HCC is recommended. Further studies on larger numbers of patients are needed before this strategy is adopted.     

Hepatic precancerous lesions and small hepatocellular carcinoma

Precancerous lesions that may be detected in chronically diseased, usually cirrhotic livers, include: clusters of hepatocytes with atypia and increased proliferative rate (dysplastic foci) that usually represent an incidental finding in biopsy or resection specimens; and grossly evident lesions (dysplastic nodules) that may be detected on radiologic examination. There are two types of small hepatocellular carcinoma (HCC) (defined as HCC that measures less than 2 cm): early HCC, which is well-differentiated and has indistinct margins; and distinctly nodular small HCC, which is well- or moderately differentiated, and is usually surrounded by a fibrous capsule. Precise diagnosis of precancerous and early cancerous lesions by imaging methods is often difficult or impossible. Detection of a dysplastic lesion in a biopsy specimen is a marker of increased risk for HCC development, and warrants increased surveillance. High-grade dysplastic nodules and small HCCs should be treated by local ablation, surgical resection, or liver transplantation.     

Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology

Recurrence after successful surgical or nonsurgical treatment of hepatocellular carcinoma (HCC) is caused either by intrahepatic metastasis or by metachronously multicentric occurrence. Intrahepatic metastasis is a major cause of recurrence of advanced HCCs with varying degrees of vascular invasion, and multicentric occurrence is a frequent cause of recurrence in small HCCs with no obvious vascular invasion. It is estimated that at least 20% of small HCCs have a high probability of recurrence due to multicentric occurrence, based on the finding that adenomatous hyperplasia (AH) and/or atypical adenomatous hyperplasia (AAH), which are considered premalignant lesions, are found in the vicinity of resected small HCCs with liver cirrhosis. However, because neither AH nor AAH occur in HCC cases without liver cirrhosis, most recurrence of HCC in noncirrhotic liver is considered to be due to intrahepatic metastasis or to de novo hepatocarcinogenesis. In a survey of autopsy cases of liver cirrhosis with small HCC, smaller HCC nodules were found in other liver slices in 50% of cases, and it is estimated that approximately 50% of HCC is already multicentric in the early stage.     

Clathrin heavy chain (CHC) staining for the diagnosis of small hepatocellular carcinoma

The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs (≤ 2 cm) and nonsmall HCCs by core biopsy with a 20- to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.8%). The panel specificity was analyzed with the adjacent/extranodular cirrhotic liver (n = 30) and low-grade (n = 15) and high-grade dysplastic nodules (n = 16) as a control group. Absolute specificity (100%) for HCC was obtained only when at least two of the markers were positive (which two markers were positive did not matter). The addition of CHC to the panel increased the diagnostic accuracy for small HCCs (from 76.9 to 84.3%), and there was an important gain in sensitivity (from 46.8 to 63.8%). The four-marker panel had lower rates of accuracy (67.4%) and sensitivity (50%) for small G1 HCCs vs. nonsmall G1 HCCs (93.9 and 88.2%, respectively). In seven cases (including six small G1 HCCs), there was no staining with any of the markers. Cirrhotic control livers were stained for CHC in four cases (13.3%) and for GPC3 in one case (3.3%). Conclusion. The addition of CHC to the panel supports the diagnosis of small HCCs in challenging nodules on thin core biopsy samples. Small G1 HCCs include a group of earlier tumors characterized by a more silent phenotype and the progressive acquisition of the markers under study. The search for additional markers for early HCC diagnosis is warranted.

Comment

Hepatocellular carcinoma (HCC), the most frequent type of primary liver cancer, is the fifth most common solid tumor and the third most common cause of cancer mortality.¹ The American Association for the Study of Liver Diseases (AASLD) guide-lines¹ suggest that the diagnosis of HCC can be made without a tissue biopsy in patients with chronic liver disease and cirrhosis who have a mass between 1-2 cm in size if a mass shows characteristic radiologic features on at least two dynamic imaging techniques. Lesions showing typical features by both imaging techniques should be treated as HCC.² However, if the results of the two techniques are discordant or if both techniques give atypical results, then a tissue biopsy is required to confirm the diagnosis. If the lesion is larger than 2 cm, only a single dynamic imaging study is necessary to confirm the diagnosis if the findings are typical of HCC. If the findings are not typical, a biopsy should be performed. This recommendation has been supported by a prospective validation.³In addition to morphological examination an immunohistochemistry (IHC) panel of three markers of malignant transformation [Glypican-3 (GPC3), heat shock protein 70 (HSP70) and glutamine synthetase (GS)] has been endorsed by the AASLD² to aid in the detection of malignancy in both surgical and liver biopsy specimens.^4,5 The presence of any two positive IHC markers of malignant transformation displayed a sensitivity of 72% and a specificity of 100% for detecting malignancies in surgical specimens.⁴ In contrast the presence of two positive IHC marker of malignant transformation displayed a sensitivity of 50% in liver biopsies with a specificity of 100%.⁵The present article attempts to improve the sensitivity levels of the above mentioned 3-panel IHC approach for the diagnosis of small HCC in liver biopsies, by the addition of clathrin heavy chain (CHC). CHC, an endothelial marker, appears to be overexpressed in HCC and has already shown promising results in surgical specimens, especially in combination with GPC3.⁶A total of 86 HCCs were evaluated: forty seven small HCCs (< 2 cm) and 39 non-small HCCs (> 2 cm). The authors state that the diagnosis of the 86 cases was conducted based on morphologic features obtained by examination of H&;E sections. However, no morphologic criteria to distinguish low-grade dysplastic from high-grade dysplastic nodules and HCC are provided. Given the difficulty of distinguishing low grade dysplastic nodules from well differentiated HCC in liver biopsies on morphological grounds, failure to include such criteria raises the question on whether the authors consider dysplastic nodules small HCCs.CHC staining was absent in non-malignant lesions, but if positive with another marker of the 3-panel IHC system appeared to increase the sensitivity to detect small HCC lesions by 17%. The accuracy of diagnosis however, was still only within the 70 to 80% range, in contrast to a 100% accurate diagnosis obtained on H&;E examination in this study set. Furthermore, the authors observed a diagnostic accuracy of 73% when four markers were positive, and 90% when only one marker was used in the non small HCC lesions - this is difficult to understand.While the addition of CHC may improve the sensitivity in certain lesions it is doubtful from a practical perspective whether this observation warrants an introduction of CHC into the currently recommended IHC-panel.Aside from the challenges associated with validating and maintaining accurate IHC results, we feel very strongly that IHC can only function as an adjunct to clinical, radiological and morphological observations for the diagnosis of small HCC, especially in the setting of liver biopsies.     

Multicentric occurrence of hepatocellular carcinoma: In terms of pathology study

The remarkable advances in diagnostic techniques and in the pathomorphologic study of minute hepatocellular carcinomas (HCCs) in the early stage indicate that many HCCs are multicentric in origin. Morphologically, combinations of HCC nodules and other nodules, such as adenomatous hyperplasia containing cancerous foci, well-differentiated HCC, or well-differentiated HCC containing moderate or poorly differentiated cancerous tissue are considered to originate and proliferate in situ. These combinations are considered to be HCC of synchronous multicentric origin. We found that, in HCC associated with liver cirrhosis, 6 of 74 consecutively resected HCCs (8.3%) and 4 of 8 autopsy cases (50%) satisfied the above criteria for multicentric origin. This discrepancy between surgical and autopsy cases can be explained thus: In surgical cases, morphologic examination is limited to only the vicinity of the main tumor and patients with multiple minute tumors HCC tend not to be sent to the operation table. Thus, the frequency seen in autopsy cases may reflect the true figures for multicentric origin. In 94 HCCs associated with chronic hepatitis, we found none showing coexistence of the above nodules that are suggestive of synchronous multicentric origin.     

Magnetic resonance imaging of the cirrhotic liver: An update

Noninvasive imaging has become the standard for hepatocellular carcinoma(HCC) diagnosis in cirrhotic livers. In this review paper, we go over the basics of MR imaging in cirrhotic livers and describe the imaging appearance of a spectrum of hepatic nodules marking the progression from regenerative nodules to low- and high-grade dysplastic nodules, and ultimately to HCCs. We detail and illustrate the typical imaging appearancesof different types of HCC including focal, multifocal, massive, diffuse/infiltrative, and intra-hepatic metastases; with emphasis on the diagnostic value of MR in imaging these lesions. We also shed some light on liver imaging reporting and data system, and the role of different magnetic resonance imaging(MRI) contrast agents and future MRI techniques including the use of advanced MR pulse sequences and utilization of hepatocyte-specific MRI contrast agents, and how they might contribute to improving the diagnostic performance of MRI in early stage HCC diagnosis.     

Diagnostic challenges and recent advances in the early management of invasive fungal infections

During the past 20 yr, the population of immunocompromized patients at risk of developing invasive fungal infections (IFIs) has increased, and there has been a shift in fungal epidemiology, with more infections caused by non‐Aspergillus molds and yeasts, which are often resistant to one or more antifungal drugs. Traditional diagnostic methods, such as culture and the histopathology of infected tissue, often fail to detect IFIs until the later stages. Furthermore, invasive diagnostic methods to obtain tissue may be contraindicated in severely ill patients; even when tissue is available, the morphology of several filamentous fungi is identical, or the cultures may fail to grow the pathogen. Recently developed non‐invasive diagnostic techniques, such as tests for serum markers and polymerase chain reaction assays, may allow for earlier and more accurate diagnoses – crucial in the effort to reduce morbidity and the risk of mortality. This article reviews current approaches to diagnosis and treatment, focusing on how an early and accurate diagnosis can guide treatment and improve outcomes. Strategies for improving the management of IFIs also are discussed.     

Selection criteria for liver resection in patients with hepatocellular carcinoma and chronic liver disease

Hepatocellular carcinoma （HCC） is one of the most common malignancies worldwide with an annual occurrence of one million new cases. An etiologic association between HBV infection and the development of HCC has been established with a relative risk 200-fold greater than in non-infected individuals. Hepatitis C virus is also proving an important predisposing factor for this malignancy with an incidence rate of 7% at 5 years and 14% at 10 years. The prognosis depends on tumor stage and degree of liver function, which affect the tolerance to invasive treatments. Although surgical resection is generally accepted as the treatment of choice for HCC, new treatment strategies, such as local ablative therapies, transarterial embolization and liver transplantation, have been developed nowadays. With increasing detection of small HCCs from screening programs for cirrhotic patients, it is foreseen that locoregional therapy will play an important role in the near future.     

血清microRNA检测在肝细胞癌诊断中的研究进展

随着肝细胞癌(HCC)患病率和病死率的逐渐上升,寻找精确、简便易行而无创的早期诊断标志物越来越重要。小分子RNA(microRNAs,miRNAs)是一类内源性非编码的小RNA,广泛存在于动物、植物和病毒中,并且在血清和组织中均稳定表达。介绍了miRNAs作为促癌基因和抑癌基因在肿瘤发生和发展中的作用,总结了多种血清miRNAs在肝细胞癌中的异常表达情况。分析表明可以利用这些稳定表达的miRNAs作为早期诊断肿瘤的无创性标志物。     

Diagnostic sensitivity of hepatocellular carcinoma imaging and its application to non-cirrhotic patients

Background and Aims: The American Association for the Study of Liver Disease issued guidelines that proposed that hepatocellular carcinoma (HCC) can be diagnosed if a mass is larger than 2 cm in a cirrhotic liver and shows typical features of HCC at triphasic liver computed tomography (CT) or dynamic magnetic resonance imaging (MRI). In non‐cirrhotic livers, the criteria were not applicable. The aim of the present study was to retrospectively analyze the sensitivity of imaging by samples of definite HCC postoperatively and test their application to diagnose HCC in non‐cirrhotic livers. Methods: From January 2006 to November 2008, a total of 343 pathologically‐diagnosed HCC patients via surgical resection were reviewed. Among the 343 patients, 204 patients had undergone liver CT examination, and 80 patients underwent MRI examination; serum α‐fetoprotein had been checked for all 343 patients prior to operation. The diagnostic sensitivity of HCC by imaging was evaluated and compared in patients with/without cirrhosis by ultrasound and histology. Results: The diagnostic sensitivity of HCC by single imaging was approximately 65–80% (liver CT or MRI). A higher sensitivity of HCC diagnosis was found in patients with ultrasound‐diagnosed cirrhosis than non‐cirrhosis, but the difference in sensitivity disappeared after histologically‐cirrhotic validation. The results indicated that regardless of the presence or absence of cirrhosis (histology), a typical vascular pattern could diagnose HCC with equally high sensitivity. Conclusions: We provide evidence that the sensitivity of HCC diagnosis by imaging is not influenced by the cirrhotic background. Further study is needed to validate the specificity and accuracy.     

Früherkennung des hepatozellulären Karzinoms

Screening for hepatocellular carcinoma (HCC) in risk groups increases the percentage of small HCCs which are potentially eligible for curative treatment options. The present method of choice is 6 monthly ultrasound examinations of the liver. All suspect lesions greater than 1 cm in diameter should undergo further investigation by contrast-enhanced imaging techniques including ultrasound, CT and MRI, if the patient potentially qualifies for a (curative) treatment. In lesions greater than 2 cm one contrast-enhanced technique is sufficient to make the diagnosis of HCC. Lesions 1–2 cm in diameter should be diagnosed by two techniques showing a HCC-specific vascular profile. Any atypical imaging pattern should trigger a diagnostic evaluation by (guided) biopsy of the suspect lesion. If imaging and biopsy remain inconclusive the follow-up may be intensified and early re-biopsy can be considered. Very small lesions <1 cm require a close 3-monthly ultrasound examination for up to 2 years if stable or regressive, in the case of a progressive disease course further specific HCC diagnosis should be initiated as outlined.     

Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma

The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs (≤2 cm) and nonsmall HCCs by core biopsy with a 20- to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.8%). The panel specificity was analyzed with the adjacent/extranodular cirrhotic liver (n = 30) and low-grade (n = 15) and high-grade dysplastic nodules (n = 16) as a control group. Absolute specificity (100%) for HCC was obtained only when at least two of the markers were positive (which two markers were positive did not matter). The addition of CHC to the panel increased the diagnostic accuracy for small HCCs (from 76.9% to 84.3%), and there was an important gain in sensitivity (from 46.8% to 63.8%). The four-marker panel had lower rates of accuracy (67.4%) and sensitivity (50%) for small G1 HCCs versus nonsmall G1 HCCs (93.9% and 88.2%, respectively). In seven cases (including six small G1 HCCs), there was no staining with any of the markers. Cirrhotic control livers were stained for CHC in four cases (13.3%) and for GPC3 in one case (3.3%). CONCLUSION: The addition of CHC to the panel supports the diagnosis of small HCCs in challenging nodules on thin core biopsy samples. Small G1 HCCs include a group of earlier tumors characterized by a more silent phenotype and the progressive acquisition of the markers under study. The search for additional markers for early HCC diagnosis is warranted.     

Recent advances in medical management of hepatocellular carcinoma

Transcatheter arterial therapies for hepatocellular carcinoma (HCC) have developed during the last decade. A fine powder formulation of cisplatin and the new platinum agent miriplatin became standard medicines in addition to anthracyclines in transcatheter arterial chemoembolization (TACE) in Japan. Recent prospective and retrospective studies supported the usefulness of platinum agents as a chemotherapeutic at the time of varied TACE therapy. Although balloon‐occluded TACE is an effective therapy for localized HCC and drug‐eluting microspheres seemed to show a higher response rate in certain HCCs, the definite advantages of those procedures still remain uncertain. Intermediate stage HCC, or Barcelona Clinic Liver Cancer stage B, is regarded as a heterogeneous category with a wide spectrum of tumors and patients, and several subclassifications of the stage have been proposed to show different prognoses; there are also different recommended therapies in each subgroup. Authors have subclassified patients based on combinations of tumor size, tumor number, and liver function, with or without performance status. Because of differences of available medical resources and techniques in treatment procedures between countries, the most ideal and useful subgrouping remains inconclusive at present. Recently, a few systemic chemotherapies proved to be effective for advanced stage HCC in phase III studies: lenvatinib as the first line of therapy, and regorafenib, cabozantinib, and ramucirumab as second‐line therapy. Other molecular‐targeted and immune‐oncological medicines are expected to follow in the near future. Some studies have suggested an advantage of early introduction of molecular‐targeted therapy for TACE‐resistant HCC in the intermediate stage.     

Early hepatocellular carcinoma and dysplastic nodules

It has been established that small, equivocal nodular lesions such as dysplastic nodules (DNs) and small well-differentiated hepatocellular carcinomas (early HCCs) are frequently observed in noncancerous liver tissues resected along with HCCs and in explant cirrhotic livers. DNs are classified into low-grade DNs or high-grade DNs on the basis of cytological and architectural atypia; high-grade DNs show varying degrees of cytological or architectural atypia, or both. Early HCCs are indistinctly nodular and highly differentiated and are frequently difficult to differentiate from high-grade DNs. Although the pathological diagnosis of high-grade DNs and early HCCs is controversial, the presence of tumor cell invasion into the intratumoral portal tracts (stromal invasion) is a helpful clue for differentiating early HCC from high-grade DNs. It is highly suggested that many HCCs occurring in cirrhotic liver arise in DNs and develop to classical HCC in a multistep fashion.     

Histopathology of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide.Its etiology is usually linked to environmental,dietary or lifestyle factors.HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed.Although this process is yet to be completely understood,this changing scenario also has impact on the material seen by pathologists,presenting them with new diagnostic dilemmas.Histopathologic criteria for diagnosing classical,progressed HCC are well established and known,but with an increase in detection of small and early HCCs due to routine screening programs,the diagnosis of these small lesions in core needle biopsies poses a difficult challenge.These lesions can be far more difficult to distinguish from one another than progressed HCC,which is usually a clear cut hematoxylin and eosin diagnosis.Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO.This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification.Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.     

Local injection therapy for hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world and ranks the third most common cause of cancer-related death. Surgical resection, liver transplantation and percutaneous ablation are generally considered the only curative treatment for early stage HCC. Besides the limitations of insufficient organ donors and a long waiting time for liver transplantation, however, resection is applied only to patients with good hepatic reserve and localized tumors, with a resectability of 30%. DATA SOURCES: Local ablation therapy, which is minimally invasive but contributes to the significant improvement of survival in patients with unresectable tumor, hasbeen widely used in treating small HCC. Among the techniques of local therapy, percutaneous ethanol injection (PEI) with a complete response in 80% of HCCs less than 3 cm has been accepted as an alternative to surgery in patients with small HCC. Moreover, percutaneous hepatic quantified ethanol injection (PHQEI) or PEI according to the standard criteria has been confirmed to benefit patients with HCC, especially when quantified ethanol is given at a short interval (QESI, the interval was 2-3 days). RESULT: Several limitations related to local percutaneous methods may result in incomplete therapeutic effect in case of larger HCC nodules (>3 cm). CONCLUSION: The combined use of different methods according to the clinical status of patients or tumors may be essential to the effective treatment of HCC.