A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%-30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC

Local control of hepatocellular carcinoma and colorectal liver metastases after surgical microwave ablation without concomitant hepatectomy

Purpose Microwave ablation (MWA) is an accepted technique in the multimodal treatment of hepatocellular carcinoma (HCC) and colorectal liver metastases (CRLM). Study endpoints were to evaluate the local efficacy of surgical MWA in selected patients with oligonodular disease without the combination of liver resection to allow a clear interpretation of the follow-up imaging and compare it to the results on percutaneous MWA available in the literature. Methods Consecutive MWA-only procedures performed between May 2013 and May 2018 for HCC and CRLM with free-hand ultrasound guidance were identified. MWA systems with 2450 MHz were used. Incomplete ablation (IA) was defined as residual disease within 1 cm of the ablation site at the first post-ablation imaging and local recurrence (LR) as the presence of disease after at least one tumor-free imaging. Results A total of 70 tumors in 47 patients were treated with 46 laparoscopic and 1 open procedures. Each patient had no more than 3 tumors, and median size of the lesions was 15 mm (IQR: 10-22). After a median follow-up of 26 months (IQR: 12-40), IA rate was 8.6% and LR rate was 29.4%. Multivariable analysis showed that vascular proximity (OR = 3.4; 95% CI = 1.26-9.22; p=0.016) was the only significant predictor of the combined outcome IA or LR. Discussion In the present study, after mostly laparoscopic MWA, LR was higher than the rates available in the literature for percutaneous MWA of HCC but lower than in the limited studies analyzing isolated percutaneous MWA of liver metastases. Future developments may help establish the role of each therapeutic modality per tumor, in order to improve the outcomes

Three-dimensional ultrasound image-guided robotic system for accurate microwave coagulation of malignant liver tumours

Background The further application of conventional ultrasound (US) image-guided microwave (MW) ablation of liver cancer is often limited by two-dimensional (2D) imaging, inaccurate needle placement and the resulting skill requirement. The three-dimensional (3D) image-guided robotic-assisted system provides an appealing alternative option, enabling the physician to perform consistent, accurate therapy with improved treatment effectiveness. Methods Our robotic system is constructed by integrating an imaging module, a needle-driven robot, a MW thermal field simulation module, and surgical navigation software in a practical and user-friendly manner. The robot executes precise needle placement based on the 3D model reconstructed from freehand-tracked 2D B-scans. A qualitative slice guidance method for fine registration is introduced to reduce the placement error caused by target motion. By incorporating the 3D MW specific absorption rate (SAR) model into the heat transfer equation, the MW thermal field simulation module determines the MW power level and the coagulation time for improved ablation therapy. Two types of wrists are developed for the robot: a ‘remote centre of motion’ (RCM) wrist and a non-RCM wrist, which is preferred in real applications. Results The needle placement accuracies were < 3 mm for both wrists in the mechanical phantom experiment. The target accuracy for the robot with the RCM wrist was improved to 1.6 ± 1.0 mm when real-time 2D US feedback was used in the artificial-tissue phantom experiment. By using the slice guidance method, the robot with the non-RCM wrist achieved accuracy of 1.8 ± 0.9 mm in the ex vivo experiment; even target motion was introduced. In the thermal field experiment, a 5.6% relative mean error was observed between the experimental coagulated neurosis volume and the simulation result. Conclusion The proposed robotic system holds promise to enhance the clinical performance of percutaneous MW ablation of malignant liver tumours. Copyright © 2010 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78054/1/313_ftp.pd

HCC in Cirrhotic and Non-cirrhotic Liver: Timing to Surgery and Outcome - State of the Art

In this chapter we aim at presenting the state of the art in liver surgery. After a brief introduction about natural evolution of hepatocellular carcinoma (HCC) either in cirrhotic or non-cirrhotic patients, this manuscript will focus on planning and timing surgery: CT evaluation of the remnant liver; biopsy and ultrasonography (US) evaluation of liver disease; intraoperative US; surgical techniques, such as major and limited hepatectomies and two-stage hepatectomies, each of them in open or mini-invasive approach; and their possible complications. Follow-up and further interventions during expected recurrences will be highlighted. Our chapter will also treat topics such as patient’s quality of life, importance of multidisciplinary evaluation and the role of surgeon in it

Irreversible Electroporation in Pancreatic Cancer

Pancreatic cancer is the deadliest of the gastrointestinal tract with 5-year survival rates of less than 5%. Given common asymptomatic early disease course, most patients (50%) present with an already metastatic disease, while only 20% can undergo potentially curative resection. The remaining 30% present with locally advanced disease, defined as extended vascular encasement, where the risk of surgical therapy often outweighs its benefits. Traditional thermal local ablative modalities (RFA, MWA, or cryotherapy) have the disadvantage that they are not applicable in proximity to vital vascular structures, which are abundant in the peripancreatic region. Irreversible electroporation (IRE) is an emerging non-thermal alternative that induces apoptosis of tumor cells by the delivery of short repetitive impulses of high-voltage electric current. Given its mostly non-thermal modality, IRE is not hampered by a heat-sink effect and is applicable with little risk around vascular structures, bile and pancreatic ducts. Recent research suggests that local tumor destruction through IRE improves overall survival, progression-free survival and quality of life in patients with locally advanced pancreatic cancer

Bridging and downstaging therapy in patients suffering from hepatocellular carcinoma waiting on the list of liver transplantation

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