Lokalablative Therapien zur Behandlung des hepatozellul?ren Karzinoms

Hepatocellular carcinoma (HCC) is the fifth most common tumor worldwide and only 5?C10% of patients can be successfully treated by resection or liver transplantation. All other patients should receive local ablative therapy when possible but an underlying liver cirrhosis is often a limiting factor. Transarterial chemoembolization, radiofrequency (thermal) ablation and selective intra-arterial radiotherapy are the most important local ablative therapies nowadays. The Barcelona clinic liver cancer (BCLC) staging system is the most important guideline for the treatment of HCC in Europe, considering it as a dynamic guideline as the stage of the disease in each patient might change several times.     

Radiofrequency combined with immunomodulation for hepatocellular carcinoma: State of the art and innovations

Hepatocellular carcinoma(HCC) is the most common primary liver tumor and has been considered a very immunogenic tumor. The treatment with radiofrequency ablation(RFA) has been established as the standard ablative therapy for early HCC, and is currently recognized as the main ablative tool for HCC tumors 5 cm in size; however, progression and local recurrence remain the main disadvantages of this approach. To solve this clinical problem, recent efforts were concentrated on multimodal treatment, combining different strategies, including the combination of RFA and immunotherapy. This article reviewed the combination treatment of RFA with immunotherapy and found that this treatment strategy leads to an increased response of anti-tumor T cells,significantly reduces the risk of recurrence and improves survival rates compared to RFA alone. This review highlighted scientific evidence that supports the current recommendations for pre-clinical studies, and discuss the need for further research on this topic.     

Laser ablation for small hepatocellular carcinoma: State of the art and future perspectives

During the last two decades, various local thermal ablative techniques for the treatment of unresectable hepatocellular carcinoma(HCC) have been developed. According to internationally endorsed guidelines, percutaneous thermal ablation is the mainstay of treatment in patients with small HCC who are not candidates for surgical resection or transplantation. Laser ablation(LA) represents one of currently available loco-ablative techniques. In this article, the general principles, technique, image guidance, and patient selection are reported. Primary effectiveness, long-term outcome, and complications are also discussed. A review of published data suggests that LA is equivalent to the more popular and widespread radiofrequency ablation in both local tumor control and long-term outcome in the percutaneous treatment of early HCC. In addition, the LA technique using multiple thin laser fibres allows improved ablative effectiveness in HCCs greater than 3 cm. Reference centres should be equipped with all the available techniques so as to be able to use the best and the most suitable procedure for each type of lesion for each patient.     

Localized hepatocellular carcinoma: Therapeutic options

Hepatocellular carcinoma (HCC) is among the most common malignancies worldwide. Recent surveillance programs have allowed early detection and diagnosis, but overall survival of patients with HCC remains poor. This article provides a definition for localized HCC and summarizes the array of treatments that have emerged and the salient literature and findings for each. Among the treatments reviewed here are surgical resection, orthotopic liver transplantation, and local ablative therapies such as cryosurgery, percutaneous ethanol injection therapy, and transarterial chemoembolization.     

Chemoembolization and bland embolization: a critical appraisal

Hepatocellular carcinoma is a major cause of cancer-related mortality worldwide, and most patients are not candidates for potentially curative treatment. Bland and chemoembolization are palliative options for hepatocellular carcinoma (HCC) that have been evaluated in controlled trials. Chemoembolization and perhaps bland embolization used as primary treatment for HCC in selected patients are effective at prolonging survival. The role of these therapies before surgical resection, liver transplantation, or in combination with local ablative therapy is controversial and yet unproven.     

Hepatocellular carcinoma: new options for image-guided ablation

Image-guided percutaneous ablation is currently accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when transplantation and resection are precluded. Several methods for chemical or thermal tumor destruction have been developed and tested clinically during the past two decades. The seminal technique used for local treatment of HCC has been percutaneous ethanol injection (PEI). Several studies have provided indirect evidence that PEI improves the natural history of nonsurgical patients with early-stage HCC. Its major limitation is the high rate of local recurrence. Radiofrequency (RF) ablation has been the most widely assessed alternative to PEI. Five randomized controlled trials have shown that RF ablation achieves more effective and reproducible tumor destruction than PEI, leading to a better local control of the disease. As a result, RF ablation has been established as the primary ablative modality. The value of newer thermal and non-thermal methods for local tumor treatment, such as microwave ablation, irreversible electroporation (IRE), and light activated drug therapy, should be investigated in the setting of randomized controlled trials.     

Puncture injection of para-toluenesulfonamide combined with chemoembolization for advanced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is difficult to eradicate due to its resilient nature. Portal vein is often involved in tumors of large size, which exclude the patient from surgical resection and local ablative therapy, such as percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) because they were considered neither effective nor safe. Currently, there is almost no effective treatment for HCC of such condition. As a unique antitumor agent in form of lipophilic fluid for local injection, para-toluenesulfonamide (PTS) produces mild side effects while necrotizing the tumor tissues quickly and efficiently. Being largely different from both PEI and RFA therapies, PTS can disseminate itself in tumors more easily than other caustic agents, such as alcohol. So PTS may offer additional benefit to HCCs with vascular involvement. We herein describe a 70-year-old HCC patient who was treated with the combination of PTS injection and transcatheter arterial chemoembolization, resulting in a significantly improved clinical prognosis.     

Interventional treatments for hepatocellular carcinoma

Introduction Hepatocellular carcinoma (HCC) ranks thefifth in overall frequency (the fifth in men and the eighth in women) and fourth inannual mortality. About 372 000 new cases of HCC are diagnosed each year, constituting 4.6% of all new human cancers (6.3% in men and 2.7% in women).[1] Surgical treatments including hepatic resection and liver transplantation are considered the most effective treatments of HCC. However, less than 20% of HCC can be treated surgically because of multi- foc…     

Practical management of hepatocellular carcinoma.

Primary hepatocellular carcinoma (HCC) is one of the ten commonest tumours in the world and occurs mainly in patients with cirrhosis. To date, in Western countries, curative treatment options include partial liver resection or liver transplantation in selected patients with small tumours. Unfortunately, most patients are detected with non-resectable or non-transplantable HCC due to disease extension, hepatic dysfunction or comorbid factors. These patients may benefit from local ablative therapy, such as percutaneous ethanol injection or radiofrequency ablation, with curative intent in patients with small tumours. In advanced HCC chemoembolization has a high response rate, but there is no clear evidence of a survival benefit. In this review we discuss practical considerations in the treatment of HCC and propose an algorithm for the selection of different treatment modalities.     

Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan (2009 Revised Version)

The World Health Organization (WHO) criteria and Response Evaluation Criteria in Solid Tumors (RECIST) are inappropriate to assess the direct effects of treatment on the hepatocellular carcinoma (HCC) by locoreginal therapies such as radiofrequency ablation (RFA) and transcatheter arterial chemoembolization (TACE). Therefore, establishment of response evaluation criteria solely devoted for HCC is needed urgently in the clinical practice as well as in the clinical trials of HCC treatment, such as molecular targeted therapies, which cause necrosis of the tumor. Response Evaluation Criteria in Cancer of the Liver (RECICL) was revised in 2009 by Liver Cancer Study Group of Japan based on the 2004 version of RECICL, which was commonly used in Japan. Major revised points of the RECICL 2009 is to provide TE4a (Complete response with enough ablative margin) and TE4b (complete response without enough ablative margin) for local ablation therapy. Second revised point is that setting the timing at which the overall treatment effects are assessed. Third point is that emergence of new lesion in the liver is regarded as progressive disease, different from 2004 version. Finally, 3 tumor markers including alpha‐fetoprotein (AFP) and AFP‐L3 and des‐gamma‐carboxy protein (DCP) were also added for the overall treatment response. We hope this new treatment response criteria, RECICL, proposed by Liver Cancer Study Group of Japan will benefit the HCC treatment response evaluation in the setting of the daily clinical practice and clinical trials as well not only in Japan, but also internationally.     

Laser ablation of hepatocellular carcinoma-A review

A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma（HCC） in the last decade.Laser ablation（LA） and radiofrequency ablation（RFA） are the two most widely used of these.This article provides an up to date overview of the role of laser ablation in the local treatment of HCC.General principles,technique,image guidance and patient selection are discussed.A review of published data on treatment efficacy,long term outcome and complication rates of laser ablation is included and comparison with RFA made.The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed.     

Nonoperative therapies for combined modality treatment of hepatocellular cancer: expert consensus statement

Although surgical resection and liver transplantation are the only treatment modalities that enable prolonged survival in patients with hepatocellular carcinoma (HCC), the majority of HCC patients presents with advanced disease and do not undergo resective or ablative therapy. Transarterial chemoembolization (TACE) is indicated in intermediate/advanced stage unresectable HCC even in the setting of portal vein involvement (excluding main portal vein). Sorafenib has been shown to improve survival of patients with advanced HCC in two controlled randomized trials. Yttrium 90 is a safe microembolization treatment that can be used as an alternative to TACE in patients with advanced liver only disease or in case of portal vein thrombosis. External beam radiation can be helpful to provide local control in selected unresectable HCC. These different treatment modalities may be combined in the treatment strategy of HCC and also used as a bridge to resection or liver transplantation. Patients should undergo formal multidisciplinary evaluation prior to initiating any such treatment in order to individualize the best available options.     

Hepatocellular carcinoma locoregional therapies: Outcomes and future horizons

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver and has an overall five-year survival rate of less than twenty percent. For patients with unresectable disease, evolving liver-directed locoregional therapies provide efficacious treatment across the spectrum of disease stages and via a variety of catheter-directed and percutaneous techniques. Goals of locoregional therapies in HCC may include curative intent in early-stage disease, bridging or downstaging to surgical resection or transplantation for early or intermediate-stage disease, and local disease control and palliation in advanced-stage disease. This review explores the outcomes of chemoembolization, bland embolization, radioembolization, and percutaneous ablative therapies. Attention is also given to prognostic factors related to each of the respective techniques, as well as future directions of locoregional therapies for HCC.     

Percutaneous radiofrequency ablation with artificial ascites for hepatocellular carcinoma adjacent to the diaphragm

Surgical resection is the first-line curative treatment of hepatocellular carcinoma (HCC). However most patients are unable to undergo surgical resection because of advanced tumoral stage, severe liver dysfunction or poor clinical status. Therefore, image-guided tumor ablation techniques have been introduced for the treatment of unresectable HCC. Among them, radiofrequency ablation (RFA) has been demonstrated to be an effective alternative curative therapy. However, local ablative therapy for tumors located close to structures such as the diaphragm or gastrointestinal tract is technically challenging because of the risk of collateral thermal damage to nearby structures or incomplete treatment of the HCC resulting from poor visibility on sonography. The introduction of artificial ascites can separate adjacent organs from the tumor and improve the sonic window. The aim of this study was to evaluate the feasibility, safety and efficacy of RFA with artificial ascites for HCC adjacent to the diaphragm.     

Intrahepatic distant recurrence after radiofrequency ablation for a single small hepatocellular carcinoma: Risk factors and patterns

Background. The pathogenesis of frequent intrahepatic recurrence of hepatocellular carcinoma (HCC) after surgical resection or local ablation therapy remains uncertain. Risks and patterns of intrahepatic distant recurrence (IDR) of a single, primary HCC lesion after radiofrequency (RF) ablation were examined. Methods. Ninety patients with a single primary HCC lesion of less than 3 cm who had complete RF ablation were enrolled in the study. Risk factors for IDR and the patterns of IDR after RF ablation were analyzed. Results. The median follow-up was 37.4 months. IDR was observed in 44 (48.9%) patients. The cumulative rate of IDR was 10.4%, 52.5%, and 77.0% at 1, 3, and 5 years, respectively. Univariate analysis revealed that a pretreatment serum α-fetoprotein (AFP) level of ≥50 ng/ml (P = 0.0324), a des-γ-carboxy prothrombin (DCP) level of ≥40 mAu/ml (P = 0.006), an ablative margin of <5 mm of the ablation zone (P = 0.0306), and a prothrombin time of <70% (P = 0.0188) were related to IDR. A multivariate stepwise Cox proportional hazards regression model revealed that pretreatment serum AFP and DCP level and the ablative margin were independent risk factors for IDR pretreatment. Serum DCP level ≥ 40 mAu/ml (P = 0.025), local tumor progression (P = 0.011), and ablative margin < 5 mm (P = 0.024) were related to multiple IDR. Conclusions. HCC patients with high serum AFP or DCP before RF ablation should be carefully followed up to monitor any IDR. A suffi cient ablative margin in RF ablation for HCC is required to prevent IDR.     

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.     

重视肝癌的立体定向放射消融治疗

肝细胞癌(HCC)是最常见的原发性肝脏恶性肿瘤,手术切除及肝移植被认为是目前HCC可能的治愈方法,但仅30%～40%的患者能够受益。体部立体定向放射消融治疗(SABR)是近几年应用于体部恶性肿瘤治疗的一种新的精确放疗技术,以"少分次、大剂量"改变了传统的剂量分割模式,因其提高了体部恶性肿瘤的局部控制率、延长了总生存时间而受到重视。射波刀(CK)完成的SABR放疗技术具有高精度、无创伤的优点,可完成实时追踪照射(很好地解决了肿瘤的呼吸移动对治疗的影响),获得了理想的治疗有效率和局部无进展生存率、总生存率,同时3级以上放疗毒性反应发生率很低,是一种理想的治疗技术,为进一步提高HCC的临床疗效带来了新的希望。     

Management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all malignancies and causes 1 million deaths annually. The management of HCC begins with diagnostic confirmation by radiologic imaging or histology. Staging is essential, as the choice of therapy depends on the functional state of the liver and the extent of tumor growth. Surgery, in the form of either hepatic resection or orthotopic liver transplantation, is the only potentially curative treatment. Transarterial chemoembolization is commonly used as either palliative treatment or adjunctive therapy to surgery, and a survival benefit with this therapy has just recently been demonstrated in a randomized, controlled trial. Patients with inoperable HCC may benefit from local ablative therapy that may still have curative potential in those with sufficiently small lesions and adequate liver function. For patients with advanced HCC, systemic chemotherapy has been widely employed, despite low efficacy and significant complication rate. Tamoxifen did not improve survival in large clinical trials. Gene therapy is an exciting approach to treating HCC but is still largely confined to preclinical and experimental settings.     

Stereotactic Ablative Radiotherapy (SABR/SBRT) for Hepatocellular Carcinoma

Purpose of Review

Liver-directed SABR (stereotactic ablative body radiotherapy) is emerging as an effective local therapy option for HCC (hepatocellular carcinoma). This review summarizes recent clinical progresses and proposes future directions.

Recent Findings

SABR is an effective and safe, non-invasive local therapy option for HCC in the primary and salvage treatment settings, as well as a bridge to liver transplantation in selected patients. Randomized trials comparing SABR with other locoregional modalities are currently ongoing.

Summary

Research efforts are being made toward better predicting normal tissue toxicity and tumor radiosensitivity for a tailored maximal safe treatment in HCC SABR. More recently, potential synergy with immunotherapies is of increasing interest in HCC.

     

Complete response to sorafenib in a patient with recurrent hepatocellular carcinoma

Partial hepatectomy is still the treatment of choice aiming at a cure for patients with hepatocellular carcinoma (HCC), provided that the patient can tolerate the treatment. For patients with multiple recurrent HCC after partial hepatectomy which cannot be treated by re-hepatectomy or local ablative therapy, the prognosis is extremely poor. Sorafenib is a molecular-targeted agent which has been demonstrated in two global phase III randomized controlled trials to show survival benefit for advanced HCC. Here, we present a 56-year-old patient with HCC who showed complete clinical response after sorafenib was used for tumor recurrence which developed 3 mo after partial hepatectomy. There was no evidence of progression of disease for 60 mo till now after continuous treatment with sorafenib.