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Old 04-18-2013, 10:55 AM
Dross Dross is offline
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Default New ablation technique holds promise for liver cancer patients

A new minimally invasive tumor ablation technique is providing hope for liver cancer patients who can't undergo surgery or thermal ablation, a study shows.

The study of 22 patients at the Universitatsklinikum Regensberg in Regensberg, Germany, found that irreversible electroporation (IRE) successfully destroyed tumor tissue in 70% of these patients. These patients were not responsive to conventional therapy or their tumor was in a location that was not suitable for standard treatment, said Dr. Philipp Wiggermann, lead author of the study. "If one considers that IRE was really the only option for these patients, the results are very promising," he said.

There were two major complications in the study, but neither of them was life-threatening, said Dr. Wiggermann. One patient suffered partial thrombosis of the left portal vein. "It is not clear that the IRE procedure caused the partial thrombosis, but since it appeared after the ablation treatment, it was considered as a therapy-associated side effect," he said. There was accidental injury to another patient's gallbladder during the ablation treatment. "Accidental injury to surrounding organs is a risk of all percutaneous ablation techniques. Treatment of liver tumors is especially difficult due to the respiratory movement of the diaphragm leading to continuous shifting of the organ position," said Dr. Wiggermann.

IRE disrupts the cell membrane and results in cell death. It is currently undergoing clinical investigation for treatment of malignant liver and lung lesions, Dr. Wiggermann said.

Dr. Wiggermann's study was presented April 18, 2013 at the ARRS Annual Meeting in Washington, DC.

Last edited by gdpawel : 06-17-2013 at 07:23 PM. Reason: posted full article in forum board
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Old 06-17-2013, 07:16 PM
gdpawel gdpawel is offline
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Default New medical technique punches holes in cells, could treat tumors

A large animal study has shown that certain microsecond electrical pulses can punch nanoscale holes in the membranes of target cells without harming tissue scaffolding, including that in the blood vessels - a potential breakthrough in minimally invasive surgical treatments of tumors.

The study on pigs, the first large animal trial for the irreversible electroporation (IRE) technique, is described in the February 2007 issue of the journal Technology in Cancer Research and Treatment. IRE was developed at the University of California, Berkeley, which holds a number of patents on the technology.

"I've been working in this area of minimally invasive surgery for 30 years now," said Boris Rubinsky, UC Berkeley professor of bioengineering and mechanical engineering and lead author of the paper. "I truly think that this will be viewed as one of the most important advances in the treatment of tumors in years. I am very excited about the potential of this technique. It may have tremendous applications in many areas of medicine and surgery."

Rubinsky co-authored the paper with Dr. Gary Onik, director of surgical imaging at Florida Hospital Celebration Health. They founded Oncobionic two years ago to commercialize IRE. Oncobionic is in the process of being sold to AngioDynamics, a New York-based manufacturer of medical devices for minimally invasive surgery.

It was first reported in the early 1970s that the application to cells of very fast electrical pulses - in the microsecond and millisecond range - creates an electrical field that causes nanoscale pores to open in the cell membrane. But research since then has mainly focused on reversible electroporation, which uses voltages low enough to temporarily increase the cell membrane's permeability. The holes in the cell membrane created by reversible electroporation close up shortly after treatment, allowing the cell to survive.

"This concept of reversible electroporation really caught on in modern biotechnology, especially over the last decade," said Rubinsky. "It is used primarily to help get genes and drugs into cells. The field of irreversible electroporation was pretty much forgotten."

The researchers' work on irreversible electroporation is an outgrowth of studies done on a "bionic chip" that Rubinsky and his UC Berkeley students were developing. The bionic chip merged living cell tissue with electronic circuitry. In the course of understanding whether electroporation was successful, the researchers discovered a range of electrical current that would cause permanent damage to cell membranes without generating heat and thermal damage.

Irreversible electroporation uses electrical pulses that are slightly longer and stronger than reversible electroporation. With IRE, the holes in the cell membrane do not reseal, causing the cell to lose its ability to maintain homeostasis and die.

The researchers say that IRE overcomes the limitations of current minimally invasive surgical techniques that use extreme heat, such as hyperthermia or radiofrequency, or extreme cold, such as cryosurgery, to destroy cells.
They point out that temperature damage to cells also causes structural damage to proteins and the surrounding connective tissue. For liver cancer, the bile duct is at risk for damage. For prostate cancer, the urethra and surrounding nerve tissue is often affected.

Electroporation, on the other hand, acts just on the cell membrane, leaving collagen fibers and other vascular tissue structures intact. The researchers said that leaving the tissue's "scaffolding" in place allows healthy cells to regrow far more quickly than if everything in the region was destroyed.
In the new study, the researchers set out to demonstrate that the IRE technique could produce reliable and predictable results in a large animal model. They performed the IRE surgical technique on 14 healthy female pigs under general anesthesia, using the same procedures as if the patients were human.

They used ultrasound imaging to guide the 18 gauge stainless steel electrodes to target areas in the pigs' livers. The researchers applied 2,500 volts in eight 100-microsecond pulses spaced 100 microseconds apart to create lesions in the livers. They found that the lesions were immediately apparent as dark spots on the ultrasound images, giving real-time feedback during the procedure. The livers were then examined 24 hours, three days, seven days and 14 days after surgery.

"All of the vessels, down to the microvasculature, remain intact with IRE treatment, so the healing process is amazing," said Onik, who performed the surgery for the study. "Where it might take a year for a cryosurgery lesion to resolve, IRE lesions resolved in two weeks. That has major implications in terms of monitoring what you're doing and knowing that the cancer has been killed."

Another chronic drawback of heat or cryo treatments for cancer is the difficulty in treating cells that are immediately adjacent to the blood vessels. Because blood maintains a relatively stable temperature, it actually transfers heat or cold away from a treatment area in an attempt to return the region to a normal temperature range. That means some cancerous cells might actually survive treatment.

"That counts for a lot of failures when treating liver cancers," said Onik. "With IRE, you can destroy cancerous cells right next to the blood vessels. It's a more complete treatment. In my clinical experience, this is about as good as it gets. We've been using other techniques for a long time. This provides significant improvements over other treatments."

Onik does sound a note of caution, however. "While we are obviously very excited about this advance in tumor ablation, we are in the early stages of our learning curve," he said. "Experience developing cryosurgical ablation has taught us that we undoubtedly have much more to learn, and there is always the potential for unexpected results."

Although the tissue in this study was healthy, the researchers found in a prior cell culture study that IRE effectively kills human liver cancer tissue.
The IRE technology was cleared for human use by the U.S. Food and Drug Administration in November 2006. Onik is scheduled to begin human clinical trials for IRE.
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Old 06-17-2013, 07:21 PM
gdpawel gdpawel is offline
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Default Biomedical engineers use electric pulses to destroy cancer cells

A team of biomedical engineers at Virginia Tech and the University of California at Berkeley has developed a new minimally invasive method of treating cancer.

The process, called irreversible electroporation (IRE), was invented by two engineers, Rafael V. Davalos, a faculty member of the Virginia Tech Wake Forest University School of Biomedical Engineering and Science (SBES), and Boris Rubinsky, a bioengineering professor at the University of California, Berkeley.

Electroporation is a phenomenon known for decades that increases the permeability of a cell from none to a reversible opening to an irreversible opening. With the latter, the cell will die. What Davalos and Rubinsky did was apply this irreversible concept to the targeting of cancer cells.

IRE removes tumors by irreversibly opening tumor cells through a series of short intense electric pulses from small electrodes placed in or around the body, said Davalos, who is the 2006 recipient of the Hispanic Engineer National Achievement Award for Most Promising Engineer or Scientist. This application creates permanent openings in the pores in the cells of the undesirable tissue. The openings eventually lead to the death of the cells without the use of potentially harmful chemotherapeutic drugs.

The researchers successfully ablated tissue using the IRE pulses in the livers of male Sprague-Dawley rats. We did not use any drugs, the cells were destroyed, and the vessel architecture was preserved, Davalos said.

This work was completed with three additional colleagues, Lluis Mir, director of the Laboratory of Vectorology and Gene Transfer Research of the Institut Gustave Roussy, the leading cancer research center in Europe, and of the Centre National de la Recherche Scientifique (CNRS); Liana Horowitz, a visiting scientist at UC-Berkeley; and Jon F. Edd, a doctoral candidate at UC-Berkeley. They reported the in vivo experiments in the June 2006 IEEE Transactions on Biomedical Engineering.

Oncologists already use a variety of methods to destroy tumors using heat or freezing processes, but these current techniques can damage healthy tissue or leave malignant cells. The difference with IRE is Davalos and Rubinsky were able to adjust the electrical current and reliably kill the targeted cells, "reliable killing of a targeted area with cellular scale resolution without affecting surrounding tissue or nearby blood vessels is key" Davalos said.

Now, an article by Davalos on IRE is being featured in a special issue of Technology in Cancer Research and Treatment ([url]www.tcrt.org[/url]) dedicated to this new field. Rubinsky, who earned his Ph.D. from the Massachusetts Institute of Technology, is the guest editor for this special issue, published in August, 2007.

At Virginia Tech, Davalos directs the interdisciplinary Bioelectromechanical Systems Laboratory, part of the university's Institute for Critical Technology and Applied Science (ICTAS), of which SBES is a core member. In the Bioelectromechanical Systems Laboratory, other research projects associated with utilizing the physical and electrical characteristics of cells, such as engineering methods for microfluidic single cell analysis, selective cell concentration, and image-guided surgery, broaden the understanding and potential of the field of IRE.

IRE shows remarkable promise as a minimally invasive, inexpensive surgical technique to treat cancer. It has the advantages that it is easy to apply, is not affected by local blood flow, and can be monitored and controlled using electrical impedance tomography, Davalos said. He and other researchers will continue to advance this promising method to treat cancer.
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