The latest research progress on minimally invasive treatments for hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail.Data sourcesThe data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using “minimally invasive” and “hepatocellular carcinoma” or “liver cancer” as the keywords.ResultsPercutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC.ConclusionsA variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.     

肝癌消融技术管理与多元化的肝癌消融治疗团队的构建

消融是肝癌治疗的重要手段之一。规范的消融技术、科学合理的治疗策略以及密切的团队合作是取得良好疗效的重要前提。尽管近年来肝癌消融治疗的效果随着消融技术的不断改进而逐渐提高,但肿瘤复发率仍较高,因此亟需能更好地提高肝癌消融治疗的效果和改善患者预后的治疗策略。多元化的肝癌消融治疗团队的构建是根据肝癌消融治疗的需求,在常规肝癌消融治疗团队的基础上提出的新概念。由于多元化的肝癌消融治疗团队较常规肝癌消融治疗团队具有更多的潜在优势,因此其是一个具有潜力的消融团队构建的新模式。     

介入治疗在中晚期肝癌降期中的作用

介入治疗已成为中晚期肝癌姑息治疗的主力军。与此同时,在肝癌降期领域,介入治疗也发挥着越来越重要的作用,通过局部介入治疗可使中晚期肝癌的瘤灶体积减小、数量减小使之符合肝癌移植或者切除术标准。介入降期技术包括经肝动脉化疗栓塞术、药物缓释微球、经动脉放射性栓塞治疗以及各种消融治疗技术(射频消融、微波消融、冷冻消融、酒精消融)等。最佳的介入降期策略仍未达成共识,但是通过开展高级别循证医学研究,对不同方法的最佳可获益人群进行筛选,评估不同介入降期策略对后续肝移植手术在手术难度、安全性、术后疗效等方面的影响,有望提升介入治疗在中晚期肝癌降期的效果。     

脉冲电场消融治疗房颤的现状

目前,导管消融术（catheter ablation,CA）已成为国内外治疗药物难治性房颤患者的主要方法,尤其是肺静脉隔离术（pulmonary vein isolation,PVI）,已成为CA治疗的基石。无论是导管的阻抗热损伤还是球囊的冷冻消融,两大能源仍存在膈神经损伤、心房食管瘘、心包填塞等不可逆的安全问题。脉冲电场消融（pulsed field ablation,PFA）,作为一种电脉冲能源,是治疗心律失常最新的消融技术热点话题。PFA通过释放短时程、高电压的电脉冲能量对细胞产生不可逆电穿孔,导致细胞凋亡,对心肌造成不可逆的损伤,发挥肺静脉隔离的作用。其优点主要是避免冠状动脉、食管、肺静脉及膈神经等周围组织受到损伤,比常规房颤消融方法更具有效性及安全性。本文对PFA的特点展开综述,详细阐述其治疗房颤的优势。     

Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma

Hepatocellular cancer ranks fifth among cancers and is related to chronic viral hepatitis, alcohol abuse,steatohepatitis and liver autoimmunity. Surgical resection and orthotopic liver transplantation have curative potential, but fewer than 20% of patients are suitable candidates. Interventional treatments are offered to the vast majority of patients. Radiofrequency(RFA) and microwave ablation(MWA) are among the therapeutic modalities, with similar indications which include the presence of up to three lesions, smaller than 3 cm in size, and the absence of extrahepatic disease. The therapeutic effect of both methods relies on thermal injury, but MWA uses an electromagnetic field as opposed to electrical current used in RFA. Unlike MWA, the effect of RFA is partially limited by the heat-sink effect and increased impedance of the ablated tissue. Compared with RFA, MWA attains a more predictable ablation zone, permits simultaneous treatment of multiple lesions, and achieves larger coagulation volumes in a shorter procedural time. Major complications of both methods are comparable and infrequent(approximately 2%-3%), and they include haemorrhage, infection/abscess, visceral organ injury, liver failure, and pneumothorax. RFA may incur the additional complication of skin burns. Nevertheless, there is no compelling evidence for differences in clinical outcomes, including local recurrence rates and survival.     

肝癌局部治疗——消融或切除?

肝癌是我国常见的恶性肿瘤之一,手术切除目前仍然是肝癌患者首选的根治性方法,但大部分患者由于受肿瘤大小及部位、肝功能和整体状况的影响,不能耐受手术切除。近年来,以射频和微波为代表的局部消融技术迅速发展,并在临床中广泛应用,更被誉为堪与外科切除相媲美的肝癌根治性治疗的新技术。就局部消融与外科切除在肝癌治疗中的应用和选择作一简介。     

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 t...     

The clinical effects of ultrasound-guided microwave ablation in the treatment of primary hepatic carcinoma: Protocol for a retrospective clinical observation

Instruction:Despite the continuous advancement of liver cancer diagnosis technology and level, there are still nearly two-thirds of patients with primary liver cancer that are already advanced at the time of diagnosis. Ultrasound-guided microwave ablation, as a palliative treatment for intermediate and advanced liver cancer, is currently recognized internationally Standard treatment for patients with unresectable hepatocellular carcinoma. However, recently, some scholars hold that ultrasound-guided microwave ablation does not guarantee complete inactivation of tumor lesions.Methods/design:This study will evaluate the safety and effectiveness of ultrasound-guided microwave ablation in patients with advanced hepatocellular carcinoma through retrospective analysis. This study will follow a clinical research method with consecutive enrollment. The overall survival rate, objective tumor remission rate, serum indices and incidence of adverse effects after treatment will be counted for patients.Discussion:At present, there are no good treatment options for intermediate and advanced hepatocellular carcinoma. Therefore, there is a strong demand to explore the individualized multidisciplinary combined treatment model based on ultrasound-guided microwave ablation.Trial registration:ClinicalTrials.gov, ChiCTR2100052107, Registered on 17 October 2021.     

Radiofrequency ablation of liver tumors: Actual limitations and potential solutions in the future

Over the past decade,radiofrequency ablation(RFA) has evolved into an important therapeutical tool for the treatment of non resectable primary and secondary liver tumors.The clinical benefit of RFA is represented in several clinical studies.They underline the safety and feasibility of this new and modern concept in treating liver tumors.RFA has proven its clinical impact not only in hepatocellular carcinoma(HCC) but also in metastatic disease such as colorectal cancer(CRC).Due to the increasing number of HCC and CRC,RFA might play an even more important role in the future.Therefore,the refinement of RFA technology is as important as the evaluation of data of prospective randomized trials that will help define guidelines for good clinical practice in RFA application in the future.The combination of hepatic resection and RFA extends the feasibility of open surgical procedures in patients with extensive tumors.Adverse effects of RFA such as biliary tract damage,liver failure and local recurrence remain an important task today but overall the long term results of RFA application in treating liver tumors are promising.Incomplete ablation of liver tumors due to insufficient technology of ablation needles,tissue cooling by the neighbouring blood vessels,large tumor masses and ablation of tumors in close vicinity to heat sensitive organs remain difficult tasks for RFA.Future solutions to overcome these limitations of RFA will include refinement of ultrasonographic guidance(accuracy of probe placement),improvements in needle technology(e.g.needles preventing charring)and intraductal cooling techniques.     

免疫治疗时代下的肝癌肝移植

我国大部分肝癌患者在就诊时不能获得根治性手术治疗,近年来肝癌免疫治疗的突破性进展为这些中晚期肝癌患者带来了曙光。在肝癌肝移植领域,免疫治疗更是因为在肿瘤免疫和移植免疫中扮演的双重角色而备受关注。在术前降期治疗和移植术后肿瘤复发的治疗中均有创新性的应用。在免疫治疗的时代下如何应用移植肿瘤学思维使肝癌肝移植患者获益是一个崭新的课题,这需要在临床实践中进行多学科团队协作,探讨最佳的肝癌肝移植患者治疗策略,最终改善中晚期肝癌患者的预后。     

microRNAs调控肝再生的研究现状

原发性肝癌是世界上第五大常见的肿瘤,在我国发病率极高,发病率已达十万分之二十至三十,男女比例8∶1。有研究认为主要原因是大量饮酒及肝硬化。目前治疗的方法很多,如介入法、射频消融、手术切除部分肝叶、肝移植等。随着肝移植开展的不断深入,肝再生的调控机制研究也成为热点,大多关注其启动阶段的研究,对其终止阶段研究较少,研究发现microRNAs家族成员参与了肝再生的负调控过程,这一发现为肝再生的研究提供了新的方向。     

结直肠癌肝转移的治疗进展

结直肠癌的发病率和死亡率逐年上升,肝转移是主要死因。本文阐述了目前临床上使用较多的治疗方式及进展。分为系统性治疗,包括了新辅助化疗、转化治疗和分子靶向治疗;及局部治疗,包括手术切除、放射治疗、射频消融及介入治疗等。各种治疗手段各有优缺点,多学科综合治疗团队模式的推广,将为结直肠癌肝转移患者制定出较适合的方案,实现个体化治疗。     

Immunotherapy for hepatocellular carcinoma: Current status and future perspectives

Hepatocellular carcinoma(HCC) is one of the world’s deadliest and fastestgrowing tumors, with a poor prognosis. HCC develops in the context of chronic liver disease. Curative resection, surgery(liver transplantation), trans-arterial chemoembolization, radioembolization, radiofrequency ablation and chemotherapy are common treatment options for HCC, however, they will only assist a limited percentage of patients. Current treatments for advanced HCC are ineffective and aggravate the underlying live...     

肝癌合并门静脉高压的局部消融治疗

随着多种治疗方法的综合应用,原发性肝癌患者生存期不断延长。对于合并门静脉高压的早期肝癌患者,局部消融治疗可达到长期生存,并在稳定门静脉压力,保存肝脏功能,减少并发症等方面具有积极的作用。此外,局部消融可以和经肝动脉化疗栓塞术、经颈内静脉肝内门体分流术、脾切除、贲门周围血管离断术等方法相结合,进一步提高疗效。围手术期客观评价门静脉压力,预防食管胃底静脉曲张破裂出血,纠正脾功能亢进和防止术后肝衰竭,做好多学科团队协作管理,有助于提升消融后患者的管理效率。     

Alternative techniques for the treatment of colon carcinoma metastases in the liver: current status in The Netherlands.

BACKGROUND: Review of current treatment modalities for liver metastases resulting from colorectal cancer. METHODS: Literature review. RESULTS: An increasing number of techniques are available for the treatment of colorectal liver metastases. When it is not possible to use the current gold standard, radical surgical resection, many patients can be treated with alternative techniques. Chemotherapy in its present form must be considered as purely palliative, perhaps with the exclusion of isolated liver perfusion: however, this therapy should still be considered as experimental. Most other possible treatments focus on local destruction of the metastases. This can be achieved using either immuno-guided techniques (tumor antibodies which carry a local active agent), direct local application of a toxic agent (injection) or thermo therapy, which has been applied in patients on a large scale. Thermo therapy involves either localized heating, by means or laser photocoagulation or radiofrequency or microwave ablation, or localized freezing using cryo probes. CONCLUSIONS: Local destruction of liver metastases, especially by means of thermo therapy, is feasible and safe. Currently, cryotherapy is most frequently used in patients. New treatment modalities, such as radiofrequency ablation, arc very promising but their true clinical value should be determined in a randomized clinical trial.     

Minimally invasive image-guided therapy of primary and metastatic pancreatic cancer

Pancreatic cancer is a challenging malignancy with limited treatment options and poor life expectancy. The only curative option is surgical resection, but only 15%-20% of patients are resectable at presentation because more than 50% of patients has distant metastasis at diagnosis and the rest of them has locally advanced pancreatic cancer (LAPC). The standard of care first line treatment for LAPC patients is chemotherapy with or without radiation therapy. Recent developments in minimally invasive ablative techniques may add to the treatment armamentarium of LAPC. There are increasing number of studies evaluating these novel ablative techniques, including radiofrequency ablation, microwave ablation, cryoablation and irreversible electroporation. Most studies which included pancreatic tumor ablation, demonstrated improved overall survival in LAPC patients. However, the exact protocols are yet to set up to which stage of the treatment algorithm ablative techniques can be added and in what kind of treatment combinations. Patients with metastatic pancreatic cancer has dismal prognosis with 5-year survival is only 3%. The most common metastatic site is the liver as 90% of pancreatic cancer patients develop liver metastasis. Chemotherapy is the primary treatment option for patients with metastatic pancreatic cancer. However, when the tumor is not responding to chemotherapy or severe drug toxicity develops, locoregional liver-directed therapies can provide an opportunity to control intrahepatic disease progression and improve survival in selected patients. During the last decade new therapeutic options arose with the advancement of minimally invasive technologies to treat pancreatic cancer patients. These new therapies have been a topic of increasing interest due to the severe prognostic implications of locally advanced and metastatic pancreatic cancer and the low comorbid risk of these procedures. This review summarizes new ablative options for patients with LAPC and percutaneous liver-directed therapies for patients with liver-dominant metastatic disease.     

Hepatic tumor ablation with clustered microwave antennae: the US Phase II trial

Background: Thermal ablation techniques have become important treatment options for patients with unresectable hepatic malignancies. Microwave ablation (MWA) is a new thermal ablative technique that uses electromagnetic energy to produce coagulation necrosis. We report outcomes from the first clinical trial in the United States using MWA and a 915 MHz generator. Patients and methods: Patients with unresectable primary or metastatic liver cancer were enrolled in a multi-institutional trial from March 2004 through May 2006. Demographic information, diagnosis, treatment, and outcomes were documented. Results: Eighty-seven patients underwent 94 ablation procedures for 224 hepatic tumors. Forty-two ablations (45%) were performed open, 7 (7%) laparoscopically, and 45 (48%) percutaneously. The average tumor size was 3.6 cm (range 0.5–9.0 cm). Single antenna ablation volumes were 10.0 ml (range 7.8–14.0 ml), and clustered antennae ablation volumes were 50.5 ml (range 21.1–146.5 ml). Outcome variables were measured with a mean follow-up of 19 months. Local recurrence at the ablation site occurred in 6 (2.7%) tumors, and regional recurrence occurred in 37 (43%) patients. With a mean follow-up of 19 months, 41 (47%) patients were alive with no evidence of disease. There were no procedure-related deaths. The overall mortality rate was 2.3%. Conclusions: Microwave ablation is a safe and effective technology for hepatic tumor ablation. In our study, clustered antennae resulted in larger ablation volumes. Further studies with histological confirmation are needed to verify clinical results.     

Overview on the use of recombinant human thyrotropin in thyroid cancer of follicular cell origin

Stimulation by recombinant human thyroid-stimulating hormone (rhTSH) has gained wide acceptance as an alternative to thyroid hormone withdrawal in the management of patients with differentiated thyroid cancer. RhTSH has the advantage to avoid both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the risk of cancer growth due to the long-lasting endogenous thyrotropin stimulation. RhTSH is a heterodimeric glycoprotein produced by recombinant DNA technology that has the ability to stimulate thyroglobulin production and radioiodine uptake by thyroid cells. RhTSH is now widely used in the follow-up of thyroid cancer patients in order to improve sensitivity of thyroglobulin (Tg) measurement as well as in preparation of (131)I diagnostic whole-body scan. Although initially approved only for diagnostic purposes, rhTSH has been now approved both in Europe and in the United States for remnant ablation in low-risk patients. As far as residual or metastatic cancer treatment, rhTSH has been initially used on a compassionate need basis for elderly and frailer patients and for patients in whom the withdrawal of thyroid hormone was medically contraindicated. Nowadays, there is a trend for widening the use of rhTSH in therapy, in order to avoid hypothyroidism and the concern about the effect of prolonged endogenous thyroid-stimulating hormone stimulation on cancerous cells. Unfortunately, the studies which address the efficacy of rhTSH in cancer treatment are still scarce and the opportunity of its clinical application remains controversial. In addition, rhTSH has been shown to improve the accuracy of [(18)F]-2-fluoro-deoxy-D-glucose positron emission tomography to detect non-functioning thyroid cancer. Although all studies agree on that rhTSH is much better tolerated from the clinical point of view than thyroid hormone withdrawal, there is some controversy about its comparative ability to raise Tg levels and concentrate radioiodine in cancerous thyroid cells. The aim of this paper is to review the performances of rhTSH as compared to hypothyroidism, considering Tg stimulation and diagnostic whole-body scan sensitivity during follow-up, and its effectiveness for normal remnant ablation and for therapy of metastatic disease.     

High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound(HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer.     

An update and our experience with metastatic liver disease

Metastatic liver disease remains a challenging and life-threatening clinical situation with an obscure and dismal prognosis and outcome. The liver is the most common site of metastatic spread of colorectal cancer and nearly half of the patients with colorectal cancer ultimately develop liver metastasis during the course of their diseases. Death from colorectal cancer is often a result of liver metastases. Over half of these patients die from their metastatic liver diseases. At the time of diagnosis, hepatic metastases are present in 15-25% of patients, and another 25-50% will develop metachronous liver metastases within 3 years following resection of the primary tumor. Over the last decade, there have been tremendous advances in the treatment of metastatic liver disease. Hepatic resection still remains the gold standard for the treatment of metastatic lesions which are amenable to surgery. Unfortunately, up to 40 percent of patients are identified as having additional disease at the time of exploration, and 20 percent are found to be unresectable. Regional therapies such as radiofrequency ablation, microwave ablation and cryotherapy may be offered to patients with isolated unresectable metastases. Other options like hepatic artery chemotherapy and chemoembolization, portal vein embolization and immunotherapy also play a vital role in management of metastatic liver disease when used in combination with other therapies. This article reviews the history of metastatic liver disease, epidemiology, diagnosis and various treatment modalities available for liver metastases along with our experience in management of advance metastatic liver disease.