Adverse Pregnancy Outcomes Following Cryotherapy, Thermal Ablation and Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia Treatment: A Pilot Study among Zambian Women

Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who according to literature may be at risk of adverse pregnancy outcomes. This pilot study is part of a study investigating adverse pregnancy outcomes among women who received Cryotherapy, Thermal ablation and Loop Electrosurgical Excision Procedure compared to the untreated women in Zambia. Materials and Methods: This descriptive study analyzed records of 886 (n = 443 treated and n = 443 untreated) women aged 15 - 49 years. The women were either screened with Visual Inspection with Acetic Acid or treated for Cervical Intraepithelial neoplasia at the Adult Infectious Disease Centre between January 2010 and December 2020. Women meeting the criteria were identified using the Visual Inspection with Acetic Acid screening records and telephone interviews to obtain the adverse pregnancy outcome experienced. Data were analysed using STATA version 16 to determine the prevalence and obtain frequency distribution of outcomes of interest. Univariate and multivariable binary logistic regression estimated odds of adverse pregnancy outcomes across the three treatments. Results: The respondents were aged 15 to 49 years. Adverse pregnancy outcomes were observed to be more prevalent in the treatment group (18.5%) compared to the untreated group (5.4%). Normal pregnancy outcomes were lower in the treated (46.3%;n = 443) than the untreated (53.7%;n = 443). The treated group accounted for the majority of abortions (85.2%), prolonged labour (85.7%) and low birth weight (80%), whereas, the untreated accounted for the majority of still births (72.7%). Women treated with cryotherapy (aOR = 2.43, 95% CI = 1.32 - 4.49, p = 0.004), thermal ablation (aOR = 6.37, 95% CI = 0.99 - 41.2, p = 0.052) and Loop Electrosurgical Excision Procedure (aOR = 9.67, 95% CI = 2.17 - 43.1, p = 0.003) had two-, six- and ten-times higher odds of adverse pregnancy outcomes respectively, relative to women who required no treatment. Conclusion: Adverse pregnancy outcomes are prevalent among women who have received treatment in Zambia. The findings indicate that treating Cervical Intraepithelial Neoplasia has been linked to higher chances of experiencing abortion, delivering low birth weight babies and enduring prolonged labor that may result in a caesarean section delivery. Cervical neoplasia treatments, particularly Loop Electrosurgical Excision Procedure, are associated with significantly increased odds of adverse pregnancy outcomes. It is essential to include information about prior Cervical Intraepithelial neoplasia treatment outcomes in obstetric care.

Mechanisms and therapeutic strategies to combat the recurrence and progression of hepatocellular carcinoma after thermal ablation

Thermal ablation(TA),including radiofrequency ablation(RFA)and microwave ablation(MWA),has become the main treatment for early-stage hepatocellular carcinoma(HCC)due to advantages such as safety and minimal invasiveness.However,HCC is prone to local recurrence,with more aggressive malignancies after TA closely related to TA-induced changes in epithelial-mesenchymal transition(EMT)and remodeling of the tumor microenvironment(TME).According to many studies,various components of the TME undergo complex changes after TA,such as the recruitment of innate and adaptive immune cells,the release of tumor-associated antigens(TAAs)and various cytokines,the formation of a hypoxic microenvironment,and tumor angiogenesis.Changes in the TME after TA can partly enhance the anti-tumor immune response;however,this response is weak to kill the tumor completely.Certain components of the TME can induce an immunosuppressive microenvironment through complex interactions,leading to tumor recurrence and progression.How the TME is remodeled after TA and the mechanism by which the TME promotes HCC recurrence and progression are unclear.Thus,in this review,we focused on these issues to highlight potentially effective strategies for reducing and preventing the recurrence and progression of HCC after TA.

Cystic echinococcosis of the liver and lung treated by radiofrequency thermal ablation:An ex-vivo pilot experimental study in animal models

AIM： To evaluate radiofrequency thermal ablation （RTA） for treatment of cystic echinococcosis in animal models （explanted organs）. METHODS： Infected livers and lungs from slaughtered animals, 10 bovine and two ovine, were collected. Cysts were photographed, and their volume, cyst content, germinal layer adhesion status, wall calcification and presence of daughter or adjacent cysts were evaluated by ultrasound. Some cysts were treated with RTA at 150 W, 80℃, 7 min. Temperature was monitored inside and outside the cyst. A second needle was placed inside the cyst for pressure stabilization. After treatment, all cysts were sectioned and examined by histology. Cysts were defined as alive if a preserved germinal layer at histology was evident, and as successfully treated if the germinal layer was necrotic. RESULTS： The subjects of the study were 17 cysts （nine hepatic and eight pulmonary）, who were treated with RTA. Pathology showed 100% success rate in both hepatic （919） and lung cysts （8/8）; immediate volume reduction of at least 65%; layer of host tissue necrosis outside the cyst, with average extension of 0.64 cm for liver and 1.57 cm for lung; and endocyst attached to the pericystium both in hepatic and lung cysts with small and focal de novo endocyst detachment in just 3/9 hepatic cysts. CONCLUSION： RTA appears to be very effective in killing hydatid cysts of explanted liver and lung. Bile duct and bronchial wall necrosis, persistence of endocyst attached to pericystium, should help avoid or greatly decrease in v/vo post-treatment fistula occurrence and consequent overlapping complications that are common after surgery or percutaneous aspiration, injection and reaspiration. In vivo studies are required to confirm and validate this new therapeutic approach.

A case of biliary gastric fistula following percutaneous radiofrequency thermal ablation of hepatocellular carcinoma

Percutaneous radiofrequency thermal ablation （RFA） is an effective and safe therapeutic modality in the management of liver malignancies, performed with ultrasound guidance. Potential complications of RFA include liver abscess, ascites, pleural effusion, skin burn, hypoxemia, pneumothorax, subcapsular hematoma, hemoperitoneum, liver failure, tumour seeding, biliary lesions. Here we describe for the first time a case of biliary gastric fistula occurred in a 66-year old man with a Child＇s class A alcoholic liver cirrhosis as a complication of RFA of a large hepatocellular carcinoma lesion in the nl segment. In the light of this case, RFA with injection of saline between the liver and adjacent gastrointestinal tract, as well as laparoscopic RFA, ethanol injection （PEI）, or other techniques such as chemoembolization, appear to be more indicated than percutaneous RFA for large lesions close to the gastrointestinal tract.

Thermal ablation in colorectal liver metastases: Lack of evidence or lack of capability to prove the evidence?

Many studies suggest that combined multimodality treatments including ablative therapies may achieve better outcomes than systemic chemotherapy alone in patients with colorectal liver metastases. Nevertheless, ablative therapies are not yet considered as effective options because their efficacy has never been proved by randomized controlled trials (RCT). However, there are in literature no trials that failed in demonstrating the effectiveness of ablative treatments: what are lacking, are the trials. All the attempts to organize phase III studies on this topic failed as a result of non accrual. Just one prospective RCT comparing radiofrequency ablation combined with systemic chemotherapy vs chemotherapy alone has been published. It was designed as a phase III study, but it was closed early because of slow accrual, and was downscaled to phase II study, with the consequent limits in drawing definite conclusions on the benefit of combined treatment. However, the combination treatment met the primary end point of the study and obtained a significantly higher 3-year progression-free survival than systemic chemotherapy alone. It is very unlikely that ultimate efficacy of ablation treatments will ever be tested again, and the best available evidence points toward a benefit for the combination strategy using ablative treatments and chemotherapy.

Thermal ablation for papillary thyroid microcarcinoma: Some clarity amid controversies

The increasing incidence of papillary thyroid microcarcinoma(PTMC)has become a global challenge.Because of its indolent nature,active surveillance(AS)has been proposed as a treatment option in selected PTMC patients to prevent surgery-related complications.However,only a few patients with PTMC receive the AS approach because of the serious psychological burden following the“cancer”diagnosis and the uncertainty of the timing for metastatic dissemination.Ultrasound(US)-guided thermal ablation can bridge the gap in the treatment options of PTMC patients who wish for a minimally invasive management approach.However,it has acquired only marginal attention from the thyroid guideline societies because of concerns regarding incomplete elimination.The recently published guidelines from the European Thyroid Association-Cardiovascular and Interventional Radiological Society of Europe and the American Head Neck Society Endocrine Section-initiated global consensus provide the most definitive evidence and essential foundational experience to address the long-term controversy over USguided thermal ablation for low-risk PTMC patient management and facilitate the responsible global dissemination of minimally invasive strategies.

Thermal ablation and immunotherapy for hepatocellular carcinoma:Recent advances and future directions

Hepatocellular carcinoma(HCC)is one of most common cancers that cause death in the world.Thermal ablation(TA)is an important alternative treatment method for HCC patients who are not appropriate for surgery or liver transplantation.Particularly for small and early HCCs,TA can be considered as the first-line curative treatment.However,local and distant recurrence rates are still high even though the TA equipment and technology develop rapidly.Immunotherapy is a novel systemic treatment method to enhance the anti-tumor immune response of HCC patients,which has the potential to reduce the tumor recurrence and metastasis.The combination of local TA and systemic immunotherapy for HCCs may be an ideal treatment for enhancing the efficacy of TA and controlling the recurrence.Herein we summarize the latest progress in TA,immunotherapy,and their combination for the treatment of patients with HCC and discuss the limitations and future research directions of the combined therapy.

Potential application of ultrasound-guided thermal ablation in rare liver tumors

Background: With the advances of imaging techniques, the detection rate of rare liver tumor is increased. However, the therapeutic strategies of the rare liver tumors remain limited. Methods: We analyzed twelve pathologically confirmed rare liver tumors in 8 patients. All of the patients underwent ultrasound(US) guided biopsy and subsequent thermal ablation. The tumors were ablated according to the preoperative plans and monitored by real-time US. CT/MRI fused with contrast enhanced US(CEUS) or three-dimensional(3 D) US-CEUS images were used to guide and assess the ablation zone more accurately during thermal ablation. The rate of technical efficacy was assessed based on the contrast-enhance CT/MRI(CECT/MRI) results one month after ablation. Local tumor progression(LTP), recurrence and complications were followed up and recorded. Results: Among these twelve nodules, nine were subject to US-guided thermal ablation, whereas the other three inconspicuous nodules were subject to CEUS-guided thermal ablation. Intra-procedure CT/MRI-CEUS or 3 D US-CEUS fusion imaging assessments demonstrated that the ablation zone sufficiently covered the original tumor, and no immediate supplementary ablation was required. Additionally, no major complications were observed during the follow-up period. The postoperative CECT/MRI confirmed that the technique success rate was 100%. Within the surveillance period of 13 months, no LTP or recurrence was noted. Conclusions: US-guided thermal ablation was feasible and safe for rare liver tumors. The use of fusion imaging technique might make US-guided thermal ablation as effective as surgical resection, and this technique might serve as a potential therapeutic modality for rare liver tumors in the future.

Thermal ablation for unresectable liver tumours,time to move forward?

Even with the advent of laparoscopic techniques for liver tumours,classic resections still represent a major undertaking for numerous liver lesions.The avoidance of surgery using ablative techniques has been the aim for over 20 years.Large volumes can now be rapidly treated with low morbidity with the many technical developments and modifications of the delivery probes.Despite these advances recurrences rates remain high with all of the presently available techniques.The biological and pathophysiological basis underlying may help explain their limitations and are important in understanding where they may be appropriately applied and ways in which they may be improved in the future.

Residual tumor and central lymph node metastasis after thermal ablation of papillary thyroid carcinoma: A case report and review of literature

BACKGROUND Debate exists regarding the use of thermal ablation(TA)to treat papillary thyroid carcinoma(PTC).Some studies have recommended TA as a new,ef
cient and safe technology for PTC.In this article,we report one case of a residual tumor and central lymph node metastasis(CLNM)after TA for PTC.CASE SUMMARY A 63-year-old female underwent bilateral ultrasound(US)-guided radiofrequency ablation for PTC.Three months later,she was diagnosed as thyroid cancer with suspected CLNM by US and contrast-enhanced computed tomography.The subsequent fine-needle aspiration(FNA)biopsies were negative.Due to her strong personal preference,she underwent total thyroidectomy and central lymph node dissection.Local tissue adhesion and a difficult dissection were noted during the operation.The pathology of the frozen sections during the operation was still negative.The final pathology results of paraffin-embedded sections revealed residual tumor cells at the edge of the PTC and CLNM.CONCLUSION TA may lead to a residual tumor in patients with PTC.Follow-up using US and FNA biopsy may not be adequate to evaluate the residual tumor.TA should be carefully considered in PTC treatment.

Management of hepatocellular carcinoma recurrence after liver surgery and thermal ablations:state of the art and future perspectives

Despite the improvements in surgical and medical therapy for hepatocellular carcinoma(HCC),recurrence still represents a major issue.Up to 70%of patients can experience HCC recurrence after liver resection(LR),as well as 20%of them even after liver transplantation(LT).The patterns of recurrence are different according to both the time and the location.Similarly,the risk factors and the management can change not only according to these patterns,but also according to the underlying liver condition and to the first treatment performed.Deep knowledge of such correlation is fundamental,since prevention and effective management of recurrence are undoubtedly the most important strategies to improve the outcomes of HCC treatment.Without adjuvant therapy,maintaining very close monitoring during the first 2 years in order to diagnose curable recurrence and continue this monitoring beyond 5 years because late recurrences exist,remains our only possibility today.Surgery represents the cornerstone treatment for HCC,including both LT and LR.However,new interesting therapeutic opportunities are coming from immunotherapy that has shown encouraging results also in the adjuvant setting.In such a complex and evolutionary scenario,the aim of this review is to summarize current strategies for the management of HCC recurrence,focusing on the different possible scenarios,as well as on future perspectives.

Past,present,and future perspectives of ultrasound-guided ablation of liver tumors:Where could artificial intelligence lead interventional oncology?

The first ablation procedures for small hepatocellular carcinomas were percutaneous ethanol injection under ultrasound(US)guidance.Later,radiofrequency ablation was shown to achieve larger coagulation areas than percutaneous ethanol injection and became the most used ablation technique worldwide.In the past decade,microwave ablation systems have achieved larger ablation areas than radiofrequency ablation,suggesting that the 3-cm barrier could be broken in the treatment of liver tumors.Likewise,US techniques to guide percutaneous ablation have seen important progress.Contrast-enhanced US(CEUS)can define and target the tumor better than US and can assess the size of the ablation area after the procedure,which allows immediate retreatment of the residual tumor foci.Furthermore,fusion imaging fuses real-time US images with computed tomography or magnetic resonance imaging with significant improvements in detecting and targeting lesions with low conspicuity on CEUS.Recently,software powered by artificial intelligence has been developed to allow three-dimensional segmentation and reconstruction of the anatomical structures,aiding in procedure planning,assessing ablation completeness,and targeting the residual viable foci with greater precision than CEUS.Hopefully,this could lead to the ablation of tumors up to 5-7 cm in size.

Safety and Efficacy of Physical Thermal Ablation Combined Sorafenib for Hepatocellular Carcinoma:A Meta-analysis

Background and Aims:To compare the efficacy and safety of physical thermal ablation(PTA),including radiofrequency ablation(RFA)and microwave ablation(MWA),combined with sorafenib and physical thermal ablation alone for the control and treatment of hepatocellular carcinoma(HCC)according to the available literature.Methods:Comprehensive searches were performed on PubMed,Embase,CNKI,the Cochrane Library,China Biomedical Literature Database(known as CBM),Weipu Journal,and Wanfang Database.Meta-analysis was performed using Revman 5.3 software.Results:A total of 15 studies,consisting of 2,227 HCC patients,were selected and included in this meta-analysis.Compared with the RFA-alone group,the patients in the RFA+sorafenib group had longer 1-,2-,and 3-year overall survival(all p<0.05),better overall efficacy(p<0.0001),longer radiofrequency interval(p<0.001),and lower 2-year recurrence rate(p=0.02).The 1-year overall survival(p=0.003)and overall efficacy(p=0.002)of the MWA+sorafenib group were also higher than those of the MWA-alone group.The incidences of adverse reactions in the RFA+sorafenib group,such as hand-foot skin reactions(p<0.001),diarrhea and constipation(p=0.0001),hypertension(p=0.009),and alopecia(p<0.001),were significantly higher than those in the RFA-alone group.Conclusions:RFA or MWA combined with sorafenib has produced a better therapeutic effect on HCC than physical thermal ablation alone;however,adverse reactions have been obvious.It is necessary to evaluate the safety of combination therapy,and pay close attention to the adverse reactions that develop in patients.

Intrahepatic Cholangiocarcinoma and Thermal Ablation:Long-term Results of An Italian Retrospective Multicenter Study

Background and Aims: Despite resection being considered the treatment of choice for intrahepatic cholangiocarcinoma(ICC),percutaneous thermal ablation can be an alter-native treatment for patients unfit for surgery.Our aim was to compare long-term results of percutaneous sonographi-cally-guided radiofrequency ablation(RFA)with high-powered microwave ablation(MWSA)in treatment of ICC.Methods: Results of 71 ICC patients with 98 nodules treated with RFA(36 patients)or MWSA(35 patients)between January 2008 and June 2018 in 5 Interventional Ultrasound centers of Southern Italy were retrospectively reviewed.Cu-mulative overall survival curves were calculated with the Ka-plan-Meyer method and differences with the log-rank test.Eleven possible factors affecting survival were analyzed.Results: Overall survival of the entire series was 88%,65%,45%and 34%at 12,36,60 and 80 months,respec-tively.Patients treated with MWSA survived longer than pa-tients treated with RFA(p < 0.005).The MWSA group with ICC nodules ≤3 cm or nodules up to 4 cm survived longer than the RFA group(p < 0.0005).In patients with nodules>4 cm,no significant difference was found.Disease-free sur-vival and progression-free survival were better in the MWSA group compared to the RFA group(p < 0.005).Diameter of nodules and MWSA were independent factors predicting a better survival.No major complications were observed.Conclusions: MWSA is superior to RFA in treating ICC unfit for surgery,achieving better long-term survival in small(≤3 cm)ICC nodules as well as nodules up to 4 cm of neo-plastic tumors and should replace RFA.

Ultrasound-guided microwave ablation for abdominal wall metastatic tumors: A preliminary study

AIM: To evaluate the feasibility, safety and efficacy of ultrasound-guided microwave (MW) ablation for abdominal wall metastatic tumors. METHODS: From August 2007 to December 2010, a total of 11 patients with 23 abdominal wall nodules (diameter 2.59 cm ± 1.11 cm, range 1.3 cm to 5.0 cm) were treated with MW ablation. One antenna was inserted into the center of tumors less than 1.7 cm, and multiple antennae were inserted simultaneously into tumors 1.7 cm or larger. A 21 gauge thermocouple was inserted near important organs which required protection (such as bowel or gallbladder) for real-time temperature monitoring during MW ablation. Treatment outcome was observed by contrast-enhanced ultrasound and magnetic resonance imaging (MRI) [or computed tomography (CT)] during follow-up. RESULTS: MW ablation was well tolerated by all patients. Six patients with 11 nodules had 1 thermocouple inserted near important organs for real-time temperature monitoring and the maximum temperature was 56 ℃. Major complications included mild pain (54.5%), post-ablation fever (100%) and abdominal wall edema (25%). All 23 tumors (100%) in this group were completely ablated, and no residual tumor or local recurrence was observed at a median follow-up of 13 mo (range 1 to 32 mo). The ablation zone was well defined on contrast-enhanced imaging (contrast-enhanced CT, MRI and/or contrast-enhanced ultrasound) and gradually shrank with time. CONCLUSION: Ultrasound-guided MW ablation may be a feasible, safe and effective treatment for abdominal wall metastatic tumors in selected patients.

A case of gouty arthritis following percutaneous radiofrequency ablation for hepatocellular carcinoma

Percutaneous radiofrequency thermal ablation(RFA) is considered an effective technique for providing local control in the majority of Hepatocellular carcinoma(HCC) patients.Although RFA is generally well tolerated,recent studies have reported complications associated with RFA.We describe a case of acute gouty arthritis in a 71-year-old man with chronic renal failure who was treated with RFA for a HCC lesion and who had hepatitis B-associated cirrhosis and mild renal insufficiency.Regular surveillance of the patient detected a 3.5 cm HCC lesion.Because the patient had declined surgery,RFA was chosen for therapy.On the third post-procedural day,the laboratory results showed increases in his uric acid and potassium levels,which were compatible with a tumor lysis syndrome. On the 6th post-procedural day,the patient complained of new right knee pain.Subsequent joint aspiration revealed monosodium urate monohydrate crystals.We made the diagnosis of acute gouty arthritis arising from tumor lysis and liver infarction caused by HCC ablation,which was aggravated by acute renal insufficiency. After adequate hydration and administration of oral colchicines,the patient's right knee pain subsided andthe uric acid serum level returned to normal.This is the first described case of acute gouty arthritis after RFA for a HCC lesion in a patient with underlying chronic renal insufficiency.To avoid hyperuricemia and an acute attack of gout after RFA therapy for HCC,early identification of patients at risk is warranted,such as those with a large tumor,rapid tumor growth,and renal insufficiency,and preventative measures should be considered.

Development and preclinical evaluation of multifunctional hydrogel for precise thermal protection during thermal ablation

Image-guided thermal ablation(TA),which is less invasive,has been widely applied for treating various kinds of tumors.However,TA still poses the potential risk of thermal damage to sensitive tissue nearby.Therefore,an adjunctive thermoprotective hydrodissection technique with constant injection of 5%glucose(5%Glu)has currently been adopted for clinical application,but this may be hazardous to humans.In this study,a multifunctional hyaluronic acid-based hydrogel(HA-Dc)was developed for hydrodissection.Compared with 5%Glu(the most clinically used solution)and the previously reported F127 hydrogel,the HA-Dc hydrogel was studied in vitro in a porcine liver model and in vivo in a rabbit model and showed good injectability and better tissue retention,stability,and thermoprotective properties throughout the TA procedure.Furthermore,in the preclinical evaluation in a Macaca fascicularis(M.fascicularis)model,HA-Dc showed excellent performance in terms of stricter neuroprotection compared with 5%Glu.In addition,the HA-Dc hydrogel with good biocompatibility and controllable degradation behavior in vivo could be a promising platform for thermal protection during clinical TA procedures.

Predictors of early and late hepatocellular carcinoma recurrence

Hepatocellular carcinoma(HCC)is the most frequent liver neoplasm,and its incidence rates are constantly increasing.Despite the availability of potentially curative treatments(liver transplantation,surgical resection,thermal ablation),long-term outcomes are affected by a high recurrence rate(up to 70%of cases 5 years after treatment).HCC recurrence within 2 years of treatment is defined as“early”and is generally caused by the occult intrahepatic spread of the primary neoplasm and related to the tumor burden.A recurrence that occurs after 2 years of treatment is defined as“late”and is related to de novo HCC,independent of the primary neoplasm.Early HCC recurrence has a significantly poorer prognosis and outcome than late recurrence.Different pathogenesis corresponds to different predictors of the risk of early or late recurrence.An adequate knowledge of predictive factors and recurrence risk stratification guides the therapeutic strategy and post-treatment surveillance.Patients at high risk of HCC recurrence should be referred to treatments with the lowest recurrence rate and when standardized to combined or adjuvant therapy regimens.This review aimed to expose the recurrence predictors and examine the differences between predictors of early and late recurrence.

Ablative strategies for recurrent hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the most common primary liver cancer and is the fifth leading cause of cancer death worldwide and the third leading cause of all diseases worldwide.Liver transplantation,surgical resection and ablation are the three main curative treatments for HCC.Liver transplantation is the optimal treatment option for HCC,but its usage is limited by the shortage of liver sources.Surgical resection is considered the first choice for early-stage HCC,but it does not apply to patients with poor liver function.Therefore,more and more doctors choose ablation for HCC.However,intrahepatic recurrence occurs in up to 70%patients within 5 years after initial treatment.For patients with oligo recurrence after primary treatment,repeated resection and local ablation are both alternative.Only 20%patients with recurrent HCC(rHCC)indicate repeated surgical resection because of limitations in liver function,tumor location and intraperitoneal adhesions.Local ablation has become an option for the waiting period when liver transplantation is unavailable.For patients with intrahepatic recurrence after liver transplantation,local ablation can reduce the tumor burden and prepare them for liver transplantation.This review systematically describes the various ablation treatments for rHCC,including radiofrequency ablation,microwave ablation,laser ablation,high-intensity focused ultrasound ablation,cryablation,irreversible electroporation,percutaneous ethanol injection,and the combination of ablation and other treatment modalities.

Hepatocellular carcinoma: Therapy and prevention

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, ＜5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further elucidate the molecular events underlying HCC development and to identify novel diagnostic markers as well as therapeutic and preventive targets.