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.
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Received Oct 22; Accepted Jan 6. This article has been cited by other articles in PMC. Abstract Background Pancreatic adenocarcinoma is currently the fourth-leading cause of cancer-related death. Current management involves primarily pharmacotherapy with opioid narcotics and celiac plexus neurolysis; unfortunately, both approaches offer transient relief and cause undesired side-effects.
High intensity focused ultrasound HIFU is a non-invasive thermal ablation technique that has been used to treat pancreatic cancer. This meta-analysis aims to evaluate the role of HIFU in pain palliation of advanced unresectable pancreatic adenocarcinoma. Pertinent studies were identified through the PubMed search engine using the following keywords: HIFU, pancreas, pancreatic cancer, pain and palliation.
Additional studies were included after manual search of the selected bibliographies. The I2 was calculated to assess the percentage of the total variability in the different effect size estimates that can be attributed to heterogeneity among the true effects. A rank correlation test of funnel plot asymmetry was done to assess possible publication bias.
Results The meta-analysis includes a total number of 23 studies with patients, with pancreatic cancer. The population enrolled ranges from 3 patients in the smallest series, up to 61 in the largest study.
Among patients treated with HIFU, complained of pancreatic pain before the treatment and patients experienced partial or complete pain relief after treatment. The random effects estimate of the proportion of patients with pain reduction was 0. Conclusions HIFU appears to be an effective tool for pain palliation in advanced pancreatic cancer. Studies assessing treatment in patients with pancreatic adenocarcinoma are limited by factors such as small sample sizes and heterogeneity in clinical definitions and assessments.
Prospective randomized and standardized studies are necessary to confirm the effectiveness of HIFU in relieving pain, and to evaluate for any potential impact on tumor control and patient survival.
Keywords: Pancreatic cancer, High intensity focused ultrasound, HIFU, Pain palliation, Pain relief, Non-invasive treatment, Meta-analysis Background Pancreatic cancer incidence is increasing worldwide with new cases and deaths estimated in , and is currently the fourth cause of cancer-related death [ 1 , 2 ].
It more frequently affects men between 65 and 84 years of age and occurs predominantly in the Western countries, where environmental factors may play an important role in the pathogenesis [ 3 ]. Moreover, mortality remains high even after surgery due to the high loco-regional recurrence rate and the tendency for early metastatic spread [ 7 ].
Considering the poor prognosis of these patients, the principal goals of pancreatic cancer therapy in advanced disease are to palliate symptoms and increase the overall survival. Throughout the illness and during end-of-life care, patients need comprehensive symptom control. It is often described as dull pain, sometimes with colicky spasms, and is referred to the mid back or epigastric regions [ 9 ].
Gemcitabine-based chemotherapy and chemoradiation combinations produce a limited improvement in survival, but are not very effective in pain relief and are associated with high toxicity [ 10 ]. The current management of pancreatic cancer-related pain primarily involves pharmacotherapy with opioid narcotics and celiac plexus neurolysis. Unfortunately, opioid narcotics often cause undesired side effects ranging from mild constipation to altered mental status.
Celiac plexus neurolysis is performed in patients who have severe intractable pain that is poorly controlled on opioids; however, the procedure is invasive, requiring endoscopic ultrasound or CT-guidance. Clearly, new methods are needed to both treat and palliate patients with advanced pancreatic cancer. High intensity focused ultrasound HIFU is a non-invasive imaging-guided thermal ablation technique that uses an extracorporeal transducer to deliver ultrasound energy to induce an increase of temperature in a sharply demarcated region.
Ultrasound or magnetic resonance imaging are used to assess the anatomy of the region for targeting and to provide real time feedback during ablation [ 14 ]. HIFU has a dual effect on the target tissue, inducing thermal and mechanical damage. The temperature reached is not high enough to cause an immediate necrosis of the cells, but it induces first intracellular denaturation of protein, and thus of the stored pancreatic enzymes, followed by cellular degeneration and necrosis.
In addition to thermal effects, there are three mechanical effects associated with high intensity acoustic energy: cavitation, microstreaming and radiation force.
Cavitation results from the oscillating motion of gas-filled bubbles stable cavitation ; these bubbles coalesce and collapse under higher ultrasound field energy, causing a shock wave confined to the microenvironment inertial cavitation [ 16 , 17 ]. Microstreaming is the consequence of stable cavitation occurring close to fluids, producing shear stress that transiently damages the cell membrane [ 18 ].
Lastly, radiation force results from the absorption or reflection of the acoustic waves by the encountered medium and can result in cellular apoptosis [ 16 , 17 ]. We aim to examine the current literature on the role of HIFU in pain palliation in advanced pancreatic cancer and to compare the methodologies used for treatment, with the goal of providing a comprehensive resource of comparable data for the design of future studies.
Methods Article search A systematic electronic search was performed using the PubMed Medline database through July Because some of the research published in this area was not written in English, it does not appear in PubMed; therefore, a manual search of the bibliographies of selected studies and reviews was completed to supplement the electronic search.
Translation of articles written in Chinese was provided by JHH.
HIFU for Palliative Treatment of Pancreatic Cancer
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.
A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound
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. Pain is often reported by patients with advanced disease, and palliative treatment methods are commonly employed and include opioid therapy and celiac plexus neurolysis 4.
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. 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.