If a patient develops gastric-outlet obstruction, treatment may include duodenal wall stents or percutaneous endoscopic gastrostomy placement for decompression. Occasionally, a patient may need surgery to create a bypass biliary bypass or gastric bypass to manage obstructive jaundice and gastric outlet obstruction. The majority of patients diagnosed with pancreatic cancer already present metastatic disease or they later develop metastatic disease. This is mainly in the liver and peritoneal cavity. This type of pain is multi-factorial and may be caused by infiltration of nerve sheaths and neural ganglia, increased ductal and interstitial pressure, and gland inflammation Staatas et al. The current management of pancreatic pain starts with non-opioid analgesics, such as nonsteroidal anti-inflammatory drugs NSAIDs , and progresses to increasing doses of opioid analgesics.
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References Ultrasound is a form of mechanical energy in which waves propagate through a liquid or solid medium e. The main parameters that are used to describe an ultrasound wave are its frequency, or the number of pressure oscillations per second, and pressure amplitude, as illustrated in Figure 2C.
Another important characteristic of an ultrasound wave is its intensity, or the amount of ultrasound energy per unit surface, which is proportional to the square of the wave amplitude. Both HIFU devices and diagnostic ultrasound imagers utilize ultrasound waves with frequencies t ypically ranging from 0. Diagnostic ultrasound probes transmit plane or divergent waves that get reflected or scattered by tissue inhomogeneities and are then detected by the same probe.
In HIFU the radiating surface is usually spherically curved, so that the ultrasound wave is focused at the center of curvature in a similar fashion to the way a magnifying lens can focus a broad light beam into a small focal spot Figure 2A. This can result in amplification of the pressure amplitude by a factor of at the focus. Another method of focusing is using ultrasound arrays, as illustrated in Figure 2B : each element of the array radiates a wave with a pre-determined phase, so that waves from all elements interfere constructively only at a desired focal point.
The size and shape of the focal region of most clinically available transducers is similar to a grain of rice: mm in diameter and mm in length. As mentioned above, diagnostic ultrasound and HIFU waves differ in amplitude. Typical diagnostic ultrasound transducers operate at the pressures of 0. For comparison, one atmosphere is equal to 0.
Ultrasound of such intensities is capable of producing both thermal and mechanical effects on tissue, which will be discussed below. Tissue heating The fundamental physical mechanism of HIFU, ultrasound absorption and conversion into heat, was first described in Absorption of ultrasound, the mechanical form of energy, in tissue is not as intuitive as absorption of electromagnetic radiation e. Tissue can be represented as viscous f luid contained by membranes.
When a pressure wave propagates through the tissue, it produces relative displacement of tissue layers and causes directional motion or microstreaming of the fluid. Viscous friction of different layers of fluid then leads to heating Both diagnostic ultrasound and HIFU heat tissue, however, since the heating rate is proportional to the ultrasound intensity, the thermal effect produced by diagnostic ultrasound is negligible. In HIFU the majority of heat deposition occurs at the focal area, where the intensity is the highest.
The focal temperature can be rapidly increased causing cell death at the focal region. However, it has been shown that this model gives good estimations of the thermal lesion dose for the higher temperatures caused by HIFU. Thus, tissue necrosis occurs almost immediately. Figure 3A shows an example of a lesion with coagulation necrosis after a single treatment with a 1 MHz HIFU device in ex vivo bovine liver. It is worth mentioning here that ultrasound absorption in tissue increases nearly linearly with ultrasound frequency; hence, more heating occurs at higher frequencies.
However, the focus becomes smaller with higher frequency 18 , and penetration depth is also limited by the higher absorption. Therefore, HIFU frequency should be chosen appropriately for smaller and shallower targets or larger targets located deeper within the body. In most applications that utilize the thermal effect of HIFU the goal is to induce cell necrosis in tissue from thermal injury. However, several studies have reported that HIFU can also induce cell apoptosis through hyperthermia, i.
In apoptotic cells, the nucleus of the cell self-destructs, with rapid degradation of DNA by endonucleases. This effect may be desirable in some cases, but may also present a limitation for HIFU ablation accuracy. Since cell death due to apoptosis occurs at lower thermal dose than thermal necrosis, the tissue adjacent to the HIFU target might be at risk from this effect Acoustic cavitation Acoustic cavitation can be defined as any observable activity involving a gas bubble s stimulated into motion by an exposure to an acoustic field.
The motion occurs in response to the alternating compression and rarefaction of the surrounding liquid as the acoustic wave propagates through it. Thus, cavitation activity in tissue may occur if the amplitude of the rarefactional pressure exceeds a certain threshold, which in turn depends on ultrasound frequency with lower frequencies having lower rarefactional pressure thresholds.
Cavitation threshold has been measured in different tissues in a number of studies, but there is still no agreement , For example, cavitation threshold in blood is estimated to be 6. Once formed, the bubble can interact with the incident ultrasound wave in two ways: stably or inertially. When the bubble is exposed to a low-amplitude ultrasound field, the oscillation of its size follows the pressure changes in the sound wave and the bubble remains spherical.
Bubbles that have a resonant size with respect to the acoustic wavelength will be driven into oscillation much more efficiently than others; for ultrasound frequencies commonly used in HIFU the resonant bubble diameter range is microns Inertial cavitation is a more violent phenomenon, in which the bubble grows during the rarefaction phase and then rapidly collapses which leads to its destruction.
The collapse is often accompanied by the loss of bubble sphericity and formation of high velocity liquid jets. If the bubble collapse occurs next to a cell, the jets may be powerful enough to cause disruption of the cell membrane 25 , In blood vessels, violently collapsing bubbles can damage the lining of the vessel wall or even disrupt the vessel altogether.
One may assume that the disruption occurs due to bubble growth and corresponding distension of the vessel wall. However, it was shown that most damage occurs as the bubble rapidly collapses and the vessel wall is bent inward or invaginated, causing high amplitude shear stress Microstreaming can produce high shear forces close to the bubble that can disrupt cell membranes and may play a role in ultrasound-enhanced drug or gene delivery when damage to the cell membrane is transient Cavitation activity is the major mechanism that is utilized when mechanical damage to tissue is a goal.
In such treatments the thermal effect is usually to be avoided, therefore, short bursts of very high amplitude ultrasound of low frequency usually below 2 MHz are used. The time-averaged intensity remains low, and the thermal dose delivered to the tissue is not sufficient to cause thermal damage. Cavitation can also promote heating if longer HIFU pulses or continuous ultrasound is used The energy of the incident ultrasound wave is transferred very efficiently into stable oscillation of resonant-size bubbles.
This oscillatory motion causes microstreaming around the bubbles and that, in turn, leads to additional tissue heating through viscous friction, which can lead to coagulative necrosis.
Nonlinear ultrasound propagation effects Nonlinear effects of ultrasound propagation are observed at high acoustic intensities and manifest themselves as distortion of the pressure waveform: a sinusoidal wave initially generated by an ultrasound transducer becomes sawtooth-shaped as it propagates through water or tissue Figure 2D. This distortion represents the conversion of energy contained in the fundamental frequency to higher harmonics that are more rapidly absorbed in tissue since ultrasound absorption coefficient increases with frequency.
As a result, tissue is heated much faster than it would if nonlinear effects did not occur. Therefore, it is critical to account for nonlinear effects when estimating a thermal dose that a certain HIFU exposure would deliver. Probably, the most important consequence of nonlinear propagation effects is that the boiling temperature of water, oC, can be achieved as rapidly as several milliseconds, which leads to the formation of a millimeter-sized boiling bubble at the focus of the transducer This changes the course of treatment dramatically: the incident ultrasound wave is now reflected from the bubble and heat deposition pattern is distorted in unpredictable manner.
The lesion shape becomes irregular, generally resembling a tadpole, as illustrated in Figure 3B. Moreover, the motion of the boiling bubble may cause tissue lysis that can be seen as a vaporized cavity in the middle of the thermal lesion. Sometimes this effect may be desirable and can be enhanced by using HIFU pulses powerful enough to induce boiling in several milliseconds, and with duration only slightly exceeding the time to reach boiling temperature In that case the temperature rise is too rapid for protein denaturation to occur, but the interaction of the large boiling bubble with ultrasound field leads to complete tissue lysis, as illustrated in Figure 3C Radiation force and streaming Radiation force is exerted on an object when a wave is either absorbed or reflected from that object.
Complete reflection produces twice the force that complete absorption does. In both cases the force acts in direction of ultrasound propagation and is constant if the amplitude of a wave is steady. However, if the medium is liquid i. This effect has important implications in sonotrombolysis, in which a clotdissolving agent is driven by streaming towards and inside the clot blocking a vessel The role of these methods in treatment is three-fold: visualization of the target, monitoring tissue changes during treatment and assesment of the treatment outcome.
In terms of tumor visualization, both MRI and sonography can provide satisfactory images; MRI is sometimes superior in obese patients 39 , but is more expensive and labor-intensive. Unfortunately, to date none of the monitoring methods can provide the image of the thermal lesion directly and in real time as it forms in tissue.
The biggest advantage of MRI is that, unlike ultrasound-based methods, it can provide tissue temperature maps overlying the MR image of the target almost in real time. The distribution of sufficient thermal dose is then calculated and assumed to correspond to thermally ablated tissue.
The temporal resolution of MR thermometry is seconds per image, and the spatial resolution is determined by the size of the image voxel which is typically about 2mm x 2mm x 6mm Therefore, MR-guided HIFU is only suitable for treatments in which the heating occurs slowly, on the order of tens of seconds for a single lesion.
Motion artifact due to breathing and heartbeat is also a concern in clinical setting. Ultrasound imaging used in current clinical devices does not have the capability of performing thermometry, but it provides real-time imaging using the same energy modality as HIFU. This is a significant benefit, because adequate ultrasound imaging of the target suggests that there is no obstruction e. One method that is sometimes used for confirmation of general targeting accuracy is the appearance of a hyperechoic region on the ultrasound image during treatment.
This region has been shown to correspond to the formation of a large boiling bubble at the focus when tissue temperature reaches oC, and underestimates the actual size of the thermal lesion since thermal lesions develop at temperatures below oC Imaging methods to assess HIFU treatment are similar to those used to assess the response to other methods of ablation such as radiofrequency ablation and include contrast enhanced CT and MRI In addition, the use of microbubble contrast-enhanced sonography is also being examined as a method to evaluate the treatment effect of HIFU These methods all examine the change in vascularity of the treated volume.
Fig 2 A A single-element HIFU transducer has a spherically curved surface to focus ultrasound energy into a small focal region in which ablation takes place, leaving the surrounding tissue unaffected. B In a phased-array HIFU transducer the position of the focus can be steered electronically by shifting the phases of the ultrasound waves radiated by each element without moving the transducer.
C An example of a linear sine ultrasound wave; its frequency spectrum contains a single frequency f. D A nonlinear ultrasound wave is formed by the energy transfer from the linear wave with the fundamental frequency f into the waves with higher frequencies also known as harmonics : 2f , 3f , etc.
Therefore, the frequency spectrum contains the fundamental frequency f as well as higher harmonics: 2f , 3f , etc. Fig 3 Examples of HIFU lesions produced in ex vivo bovine liver tissue with different sonication reigimes. A Absorption of linear ultrasound waves results in predictable cigar-shaped thermal lesion. B Irregularly-shaped thermal lesion with evaporated core results from boiling which is induced in tissue by rapid absorption of continuous nonlinear HIFU waves.
C A lesion containing liquefied tissue may be produced by very short, high-amplitude nonlinear HIFU pulses. HIFU of pancreatic tumors.
A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound
Tel: ; Fax: E-mail: ude. Copyright Journal of Gastrointestinal Oncology. All rights reserved. This article has been cited by other articles in PMC.
HIFU FOR PALLIATIVE TREATMENT OF PANCREATIC CANCER PDF
References Ultrasound is a form of mechanical energy in which waves propagate through a liquid or solid medium e. The main parameters that are used to describe an ultrasound wave are its frequency, or the number of pressure oscillations per second, and pressure amplitude, as illustrated in Figure 2C. Another important characteristic of an ultrasound wave is its intensity, or the amount of ultrasound energy per unit surface, which is proportional to the square of the wave amplitude. Both HIFU devices and diagnostic ultrasound imagers utilize ultrasound waves with frequencies t ypically ranging from 0. Diagnostic ultrasound probes transmit plane or divergent waves that get reflected or scattered by tissue inhomogeneities and are then detected by the same probe. In HIFU the radiating surface is usually spherically curved, so that the ultrasound wave is focused at the center of curvature in a similar fashion to the way a magnifying lens can focus a broad light beam into a small focal spot Figure 2A. This can result in amplification of the pressure amplitude by a factor of at the focus.
HIFU for Palliative Treatment of Pancreatic Cancer
Twelve months after the combination treatment with HIFU and chemotherapy the liver metastases were significantly reduced on the contrast control CT. Thresholds for transient cavitation produced by pulsed ultrasound in a controlled nuclei environment. HIFU for palliative treatment of pancreatic cancer The overall median survival was 8. MR imaging-controlled focused ultrasound ablation: Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer. The distribution of sufficient thermal dose is then calculated and assumed to correspond to thermally ablated tissue. Journal List J Gastrointest Oncol v.
HIFU for palliative treatment of pancreatic cancer.
Go to: Physical mechanisms underlying HIFU therapy Ultrasound is a form of mechanical energy in which waves propagate through a liquid or solid medium e. The main parameters that are used to describe an ultrasound wave are its frequency, or the number of pressure oscillations per second, and pressure amplitude, as illustrated in Figure 2C. Another important characteristic of an ultrasound wave is its intensity, or the amount of ultrasound energy per unit surface, which is proportional to the square of the wave amplitude. Figure 2 A A single-element HIFU transducer has a spherically curved surface to focus ultrasound energy into a small focal region in which ablation takes place, leaving the surrounding tissue unaffected. B In a phased-array HIFU transducer the position of the focus can be steered electronically by shifting the phases of the ultrasound waves radiated by each element without moving the transducer. C An example of a linear sine ultrasound wave; its frequency spectrum contains a single frequency f.
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