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World Journal of Gastroenterology Oct 2015Hepatocellular carcinoma (HCC), the fifth most common cancer in the world, shows increasing incidence worldwide. Curative treatments such as hepatectomy, liver... (Review)
Review
Hepatocellular carcinoma (HCC), the fifth most common cancer in the world, shows increasing incidence worldwide. Curative treatments such as hepatectomy, liver transplantation, and radiofrequency ablation are applied in only 30%-60% of cases. Most remaining patients receive transarterial chemoembolization (TACE). Patients with intermediate-stage HCCs are regarded as good candidates for TACE. However, the intermediate stage includes non-homogeneous patients. Some movements are underway to stratify patients using prognostic factors to identify patient groups exhibiting greater benefit from TACE than other patient groups. This review describes two substaging systems that subclassify intermediate-stage HCCs and discusses the importance of dividing intermediate-stage patients.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Hepatectomy; Humans; Japan; Liver Neoplasms; Medical Oncology; Neoplasm Staging; Prognosis; Severity of Illness Index; Societies, Medical
PubMed: 26457020
DOI: 10.3748/wjg.v21.i37.10604 -
Alimentary Pharmacology & Therapeutics Jun 2017Intermediate-stage hepatocellular carcinoma (HCC), for which trans-arterial chemoembolization (TACE) constitutes the standard of care, is a patient subgroup with... (Review)
Review
BACKGROUND
Intermediate-stage hepatocellular carcinoma (HCC), for which trans-arterial chemoembolization (TACE) constitutes the standard of care, is a patient subgroup with significant heterogeneity in clinical outcome. Sources of variation relate to differences in tumour burden, hepatic reserve, ethnicity and treatment modalities. Increasing research efforts have been dedicated to minimise the clinical diversity of this patient population and enhance optimal provision of treatment.
AIM
To comprehensively review the diverse prognostic models that have been proposed to refine the prognostic prediction of patients with HCC undergoing TACE.
RESULTS
A number of prognostic algorithms (HAP, ART, ABCR score and many others) have shown potential to address the clinical heterogeneity characterising patients with intermediate-stage HCC and facilitate early identification of patients with poor prognostic features in whom alternative treatments or best supportive care might be more appropriate than TACE.
CONCLUSIONS
While an improved characterisation of intermediate-stage HCC is a highly important clinical aim, current evidence suggests that novel prognostic algorithms in this patient population may offer potential benefits but non-negligible challenges in the provision of TACE. This review summarises the currently available evidence to facilitate the development of precision oncology in intermediate-stage HCC.
Topics: Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Humans; Liver Neoplasms; Medical Oncology; Neoplasm Staging; Precision Medicine; Prognosis; Treatment Outcome
PubMed: 28440552
DOI: 10.1111/apt.14066 -
Medicina (Kaunas, Lithuania) 2010Majority of patients suffering from liver tumors are not candidates for surgery. Currently, minimal invasive techniques have become available for local destruction of... (Comparative Study)
Comparative Study Review
Majority of patients suffering from liver tumors are not candidates for surgery. Currently, minimal invasive techniques have become available for local destruction of hepatic tumors. Radiofrequency ablation is based on biological response to tissue hyperthermia. The aim of this article is to review available biological data on tissue destruction mechanisms. Experimental evidence shows that tissue injury following thermal ablation occurs in two distinct phases. The initial phase is direct injury, which is determined by energy applied, tumor biology, and tumor microenvironment. The temperature varies along the ablation zone and this is reflected by different morphological changes in affected tissues. The local hyperthermia alters metabolism, exacerbates tissue hypoxia, and increases thermosensitivity. The second phase - indirect injury - is observed after the cessation of heat stimulus. This phase represents a balance of several promoting and inhibiting mechanisms, such as induction of apoptosis, heat shock proteins, Kupffer cell activation, stimulation of the immune response, release of cytokines, and ischemia-reperfusion injury. A deeper understanding of the underlying mechanisms may possibly lead to refinements in radiofrequency ablation technology, resulting in advanced local tumor control and prolonged overall survival.
Topics: Apoptosis; Catheter Ablation; Colorectal Neoplasms; DNA Fragmentation; Heat-Shock Proteins; Humans; Kupffer Cells; Liver; Liver Neoplasms; Necrosis; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm, Residual; Postoperative Complications; Temperature; Time Factors
PubMed: 20234157
DOI: No ID Found -
Experimental and Clinical... Mar 2017The use of orthotopic liver transplant for hepatocellular carcinoma was a major advance, pioneered by Thomas E. Starzl as a way to circumvent the limitations imposed on... (Review)
Review
The use of orthotopic liver transplant for hepatocellular carcinoma was a major advance, pioneered by Thomas E. Starzl as a way to circumvent the limitations imposed on the liver surgeon by the presence of cirrhosis and liver failure. Patients with a few small tumors, whatever their degree of liver damage, may expect prolonged survival (70% at 5 years). Patients with more advanced tumors have high recurrence rates and more limited survival, possibly due to immune suppression or pretransplant understaging of their tumors. Another possibility is that patients with micrometastases have a longer survival time, during which the metastases eventually become evident. Recent advances include the identification of patients using levels of tumor markers to allow more careful patient selection with better outcomes. The contributions of molecular signatures and the new, effective antiviral agents are possibly significant.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Hepatocellular; Combined Modality Therapy; Humans; Liver Neoplasms; Liver Transplantation; Molecular Diagnostic Techniques; Neoplasm Micrometastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Patient Selection; Risk Factors; Treatment Outcome; Tumor Burden
PubMed: 28301991
DOI: 10.6002/ect.TOND16.L2 -
The Keio Journal of Medicine Dec 1991With the increasing availability of curative surgical techniques for primary and secondary hepatic neoplasms, the tasks for clinical imaging of liver cancer suspects... (Review)
Review
With the increasing availability of curative surgical techniques for primary and secondary hepatic neoplasms, the tasks for clinical imaging of liver cancer suspects have become more exacting. Detection of tumor, differential diagnosis of individual nodules, and mapping the anatomic extensions of malignant disease are now routinely required. Related and unrelated liver substrate abnormalities such as cavernous hemangioma and focal fatty deposits are often discovered in liver cancer suspects and must be differentiated from metastatic deposits. Moreover, modern imaging methods frequently display tiny subcentimeter nodules which often prove difficult to adequately characterize (micrometastases vs other). The most sensitive imaging techniques are CT after arterial portography and intraoperative ultrasound, but because of their invasiveness, these are reserved exclusively for staging. For primary screening MR imaging is increasingly preferred over CT because of its superiority in discriminating hemangiomas and cysts from metastases without the need for iodinated contrast material.
Topics: Carcinoma, Hepatocellular; Forecasting; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Neoplasm Staging; Tomography, X-Ray Computed
PubMed: 1666423
DOI: 10.2302/kjm.40.194 -
Cancer Imaging : the Official... Oct 2008Our eventual aim is to predict, using non-invasive imaging techniques, the biological behaviour of individual cirrhotic nodules. We are some distance away from this, so... (Review)
Review
Our eventual aim is to predict, using non-invasive imaging techniques, the biological behaviour of individual cirrhotic nodules. We are some distance away from this, so our current objective is to define imaging features which predict the histologic findings. This short review summarises the current capabilities and limitations of non-invasive imaging in detecting small hepatocellular carcinomas (HCCs) in cirrhosis. Extracellular contrast media used with ultrasound (US), computed tomography (CT) or magnetic resonance imaging (MRI) can characterise nodules according to the predominance of arterial or portal inflow, and most HCCs will be recognised by their arterial hypervascularity. Adding intracellular (liver-specific) MRI contrast agents provides a significant improvement in early detection and in specificity for HCC. Nodules can be classified on dual contrast MRI as clearly malignant, clearly benign, or borderline (needing careful surveillance). Future imaging research needs to establish the histology of small hypervascular nodules, the evolution of hypervascular nodules and of dysplastic nodules, and to seek imaging features which predict microvascular invasion. Currently, cirrhotic patients with either suspicious nodules on screening US or rising AFP should have cross-sectional imaging with multi-phase CT or preferably MRI. Dual-contrast MRI with liver-specific agents should be used to improve diagnostic specificity for small lesions. Borderline nodules should be followed at agreed intervals using the same imaging technique each time. Pre-operative staging in surgical candidates should include CT of thorax, abdomen and pelvis and bone scintigraphy.
Topics: Carcinoma, Hepatocellular; Early Diagnosis; Humans; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Neoplasm Staging; Tomography, X-Ray Computed
PubMed: 18852086
DOI: 10.1102/1470-7330.2008.9019 -
The Oncologist 2010For patients with early-stage hepatocellular carcinoma (HCC), potentially curative treatment options exist, including liver transplantation, surgical resection, and... (Review)
Review
For patients with early-stage hepatocellular carcinoma (HCC), potentially curative treatment options exist, including liver transplantation, surgical resection, and ablation therapy. These treatments are associated with survival benefits, and outcomes are optimized by identification of appropriate patients. However, further studies are needed to definitively confirm optimal treatment approaches for all patients. Treatment patterns vary in different parts of the world as a result of geographic differences in the incidence and presentation of the disease. In particular, because of successful screening programs, a high proportion of tumors that are identified in Japan are amenable to curative treatments, which are appropriate in a smaller proportion of patients in the west, although screening is now widely carried out in industrialized countries. Differences in the applicability of transplantation are also evident between the west and Asia. Although existing treatments for early-stage HCC are supported by considerable evidence, there remain significant data gaps. For example, further data, ideally from randomized controlled trials, are needed regarding: the use of neoadjuvant and adjuvant therapy to decrease the rate of recurrence after resection or ablation, further investigation of the role of chemoprevention following resection, and prospective analysis of outcomes of living donor compared with deceased donor liver transplantation.
Topics: Ablation Techniques; Carcinoma, Hepatocellular; Humans; Japan; Liver; Liver Neoplasms; Liver Transplantation; Living Donors; Neoadjuvant Therapy; Neoplasm Staging; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome
PubMed: 21115579
DOI: 10.1634/theoncologist.2010-S4-34 -
World Journal of Gastroenterology Nov 2011Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver disease. Liver transplantation (LT)...
Hepatocellular carcinoma (HCC) is one of the most frequent neoplasms worldwide and in most cases it is associated with chronic liver disease. Liver transplantation (LT) is potentially the optimal treatment for those patients with HCC who have a poor functional hepatic reserve due to their underlying chronic liver disease. However, due to the limited availability of donors, only those patients whose oncologic profile is favorable can be considered for LT. Despite the careful selection of candidates based on strict rules, 10 to 20% of liver transplant recipients who have HCC in the native cirrhotic liver develop tumor recurrence after transplantation. The selection criteria presently employed to minimize the risk of recurrence are based on gross tumor characteristics defined by imaging techniques; unfortunately, the accuracy of imaging is far from being optimal. Furthermore, microscopic tumor features that are strictly linked with prognosis can not be assessed prior to transplantation. Pre-transplantation tumor downstaging may allow transplantation in patients initially outside the selection criteria and seems to improve the prognosis; it also provides information on tumor biology. The main peculiarity of the transplantation setting, when this is compared with other modalities of treatment, is the need for pharmacological immunosuppression: this is based on drugs that have been demonstrated to increase the risk of tumor development. As HCC is an aggressive malignancy, immunosuppression has to be handled carefully in patients who have HCC at the time of transplantation and new categories of immunosuppressive agents should be considered. Adjuvant chemotherapy following transplantation has failed to show any significant advantage. The aim of the present study is to review the possible strategies to avoid recurrence of HCC after liver transplantation based on the current clinical evidence and the more recent developments and to discuss possible future directions.
Topics: Antineoplastic Agents; Carcinoma, Hepatocellular; Humans; Immunosuppressive Agents; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Patient Selection
PubMed: 22147974
DOI: 10.3748/wjg.v17.i43.4741 -
World Journal of Gastroenterology Dec 2018A large number of liver transplants have been performed for hepatocellular carcinoma (HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver... (Review)
Review
A large number of liver transplants have been performed for hepatocellular carcinoma (HCC), and recurrence is increasingly encountered. The recurrence of HCC after liver transplantation is notoriously difficult to manage. We hereby propose multi-disciplinary management with a systematic approach. The patient is jointly managed by the transplant surgeon, physician, oncologist and radiologist. Immunosuppressants should be tapered to the lowest effective dose to protect against rejection. The combination of a mammalian target of rapamycin inhibitor with a reduced calcineurin inhibitor could be considered with close monitoring of graft function and toxicity. Comprehensive staging can be performed by dual-tracer positron emission tomography-computed tomography or the combination of contrast computed tomography and a bone scan. In patients with disseminated recurrence, sorafenib confers survival benefits but is associated with significant drug toxicity. Oligo-recurrence encompasses recurrent disease that is limited in number and location so that loco-regional treatments convey disease control and survival benefits. Intra-hepatic recurrence can be managed with graft resection, but significant operative morbidity is expected. Radiofrequency ablation and stereotactic body radiation therapy (SBRT) are effective alternative strategies. In patients with more advanced hepatic disease, regional treatment with trans-arterial chemoembolization or intra-arterial Yttrium-90 can be considered. For patients with extra-hepatic oligo-recurrence, loco-regional treatment can be considered if practical. Patients with more than one site of recurrence are not always contraindicated for curative treatments. Surgical resection is effective for patients with pulmonary oligo-recurrence, but adequate lung function is a pre-requisite. SBRT is a non-invasive and effective modality that conveys local control to pulmonary and skeletal oligo-recurrences.
Topics: Carcinoma, Hepatocellular; Clinical Protocols; Combined Modality Therapy; Humans; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local; Patient Care Team; Survival Rate; Treatment Outcome
PubMed: 30568386
DOI: 10.3748/wjg.v24.i45.5081 -
Clinical and Molecular Hepatology Oct 2021
Topics: Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Neoplasm Recurrence, Local
PubMed: 34551504
DOI: 10.3350/cmh.2021.0276