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

The sonographer’s role in RFA therapy of liver lesions

Interventional techniques using ultrasound guidance, such as Radio Frequency Ablation (RFA) of liver lesions, are the domain of the radiologist. However, real time ultrasound imaging as performed by the sonographer, is critical in monitoring the successful insertion and placement of the RFA needle. RFA is used to create a localised and controlled application of heat in order to induce necrosis of cells within the liver lesions

Focal Spot, Summer 2002

https://digitalcommons.wustl.edu/focal_spot_archives/1091/thumbnail.jp

MRI-guided focused ultrasound surgery in musculoskeletal diseases: the hot topics

MRI-guided focused ultrasound surgery (MRgFUS) is a minimally invasive treatment guided by the most sophisticated imaging tool available in today's clinical practice. Both the imaging and therapeutic sides of the equipment are based on non-ionizing energy. This technique is a very promising option as potential treatment for several pathologies, including musculoskeletal (MSK) disorders. Apart from clinical applications, MRgFUS technology is the result of long, heavy and cumulative efforts exploring the effects of ultrasound on biological tissues and function, the generation of focused ultrasound and treatment monitoring by MRI. The aim of this article is to give an updated overview on a "new" interventional technique and on its applications for MSK and allied sciences

Temperature Distribution Mapping Using an FBG-Equipped Probe for Solid Tumor Laser Ablation

In recent years, laser ablation treatments have become promising therapies for early-stage solid tumors, although the anatomical variability within the irradiated organs (i.e., presence of blood vessels and other inhomogeneities) greatly challenges the control of the tissue temperature throughout the medical procedure and thus the optical therapeutic outcome. To help getting around these limitations, a new fiber optic probe able to both deliver the laser light with optimal irradiation pattern and measure the temperature in the tumor region had been previously developed. This paper, using simulations validated with experimental data, aims at demonstrating how this probe, combined with suitable hyperthermal treatment planning, can be used to overcome the discrepancies between ex-vivo and in-vivo laser ablation procedures

Investigation of Heat Therapies using Multi-Scale Models and Statistical Methods

Ph.DDOCTOR OF PHILOSOPH

Hepatic Surgery for Colorectal Cancer Metastasis — Possibilities and Prerequisites

Colorectal cancer is among the most frequent malignant tumours. Liver metastases develop in 70–75% of patients affected by colorectal carcinoma. Nowadays, surgical treatment can significantly improve the 5-year survival ranging 40–58% of the patients undergoing liver surgery. The operation extent ranges from nonanatomic minor resection to major hepatectomy. Recently, liver transplantation has been performed for metastatic colorectal cancer. Laparoscopic approach and robotic surgery can be used by experienced specialists. The prerequisites for successful surgical treatment include exact radiologic diagnostics to determine the number and size of metastases and their association with anatomic structures; individual anatomic peculiarities and remnant liver volume, ranging 20–40% in respect to functional liver status. Magnetic resonance imaging is the most sensitive method that has marked advantages in the diagnostics of lesions smaller than 1 cm and metastases on the background of liver steatosis. Computed tomography is an acceptable alternative that benefits from high spatial resolution and optimal reconstructions to evaluate the anatomy. Additional information can be obtained from tumour markers, including traditional, e.g., carcinoembryonic antigen (CEA) and novel, e.g., microRNAs. To ensure that each colorectal cancer patient receives the best care, the medical society should be well informed about the possibilities in the treatment of liver metastases of colorectal cancer regarding the methods, indications and limits

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

Liver Segmentation and its Application to Hepatic Interventions

The thesis addresses the development of an intuitive and accurate liver segmentation approach, its integration into software prototypes for the planning of liver interventions, and research on liver regeneration. The developed liver segmentation approach is based on a combination of the live wire paradigm and shape-based interpolation. Extended with two correction modes and integrated into a user-friendly workflow, the method has been applied to more than 5000 data sets. The combination of the liver segmentation with image analysis of hepatic vessels and tumors allows for the computation of anatomical and functional remnant liver volumes. In several projects with clinical partners world-wide, the benefit of the computer-assisted planning was shown. New insights about the postoperative liver function and regeneration could be gained, and most recent investigations into the analysis of MRI data provide the option to further improve hepatic intervention planning

High-precision, non-invasive anti-microvascular approach via concurrent ultrasound and laser irradiation

Antivascular therapy represents a proven strategy to treat angiogenesis. By applying synchronized ultrasound bursts and nanosecond laser irradiation, we developed a novel, selective, non-invasive, localized antivascular method, termed photo-mediated ultrasound therapy (PUT). PUT takes advantage of the high native optical contrast among biological tissues and can treat microvessels without causing collateral damage to the surrounding tissue. In a chicken yolk sac membrane model, under the same ultrasound parameters (1 MHz at 0.45 MPa and 10 Hz with 10% duty cycle), PUT with 4 mJ/cm2 and 6 mJ/cm2 laser fluence induced 51% (p = 0.001) and 37% (p = 0.018) vessel diameter reductions respectively. With 8 mJ/cm2 laser fluence, PUT would yield vessel disruption (90%, p < 0.01). Selectivity of PUT was demonstrated by utilizing laser wavelengths at 578 nm or 650 nm, where PUT selectively shrank veins or occluded arteries. In a rabbit ear model, PUT induced a 68.5% reduction in blood perfusion after 7 days (p < 0.001) without damaging the surrounding cells. In vitro experiments in human blood suggested that cavitation may play a role in PUT. In conclusion, PUT holds significant promise as a novel non-invasive antivascular method with the capability to precisely target blood vessels.R01AR060350R01CA1867694K12EY022299-4BL2014089