Therapeutic Applications of Ultrasound
Therapeutic exploitations of ultrasound precede its utilization in tomography. Different ultrasound exposure levels help in generating and enforcing a wide diapason of biological influences. Low exposure levels help in producing medicinal reversible cellular effects, while high intensities of exposure levels lead to instant cell death. Therefore, ultrasound therapy can be extensively subdivided into ‘low’ and ‘high’ power exploitation. The first category incorporates physical therapy, fracture repair, sonophoresis, and gene therapy, while the most typical usage of the second type of ultrasound stands for high intensity focused ultrasound. In fact, both non-thermal and thermal interplay appliances generate therapeutic impact via the intensity diapason. Acoustic streaming is probable to be essential at low intensities, while heating and ultrasonic cavitation will prevail at higher levels.
HIFU Treatment for Pancreatic Cancer
The main purpose of this paper is to review and analyze recent evolvements in the usage of HIFU treatment for pancreatic cancer. This paper will also discuss and analyze HIFU potential in its application for pancreatic cancer patients.
The non-invasive abscission of pancreatic cancer through ultrasound of high intensity orientation (HIFU) output has been receiving progressively extensive interest. Due to the fact that intense temperature increases to cytotoxical levels within the nidal content of ultrasound beams, the HIFUs remove necessary impairments of the pancreas on a selective basis without damaging close surrounding or superposed tissues (Wu). The majority of preliminary researches demonstrate that this approach appears to be technically permissible, secure, and realizable and can be applied solitary, as well as being combined with systematic chemotherapy in order to treat patients who have locally advanced pancreatic cancer. This method can help in effective alleviation of cancer-connected ventral ache and might be a supplementary endurance advantage with a limited number of essential perturbations (Wu).
The facts demonstrate that carcinoma of the exocrine pancreas appears to be the fourth major cause of cancer-connected decease in the Western world and in the U.S. The U.S. 2014 statistics reveals that more than 45,000 estimated new cases were diagnosed while more than 38,000 of them had the death outcome (Wu). Due to the repeated detainment in diagnosis, approximately 80 percent of patients turn out to have metastatic or locally advanced condition, which presupposes that they are ineligible for therapeutic surgery extraction. Death appears to be a general prognosis in regards with the pancreatic cancer. Average life span in case of the locally advanced disease is mere 7-10 months; however, this estimation decreases to 4-6 months for patients who have the metastatic condition (Wu). The 5-year statistics demonstrates that the general survival ratio accounts for approximately 5 percent (Wu). Typical standard options, which are accessible for medicating the patient with inoperable pancreatic cancer, are usually restricted to radiotherapy and chemotherapy or a blend of these two options. In fact, gemcitabine stands for the most widely and commonly applied chemotherapy mediator in case of the pancreatic cancer, while innovative researches and studies demonstrate that blending of gemcitabine together with other chemotherapeutic mediators might have a restricted survival advantage for patients who have locally advanced pancreatic cancer (Zhou).
Due to the fact that a highly limited number of patients who have pancreatic cancer are typically acceptable for surgery treatment and the majority demonstrates only a minor reaction to the chemotherapeutic treatment, a high intensity focused ultrasound (HIFU) appears to be a possible supplementary treatment (Wu). Recent studies and researches demonstrate that the HIFU can significantly help with neoplasm cytoreduction in combination with a strict control of symptoms. Application of the paracorporeal approach typically stands for the utilization of focused ultrasound energy in order to elevate the temperature between 56 °C and 100 °C in a required tumor (Keane, Bramis, Pereira, & Fusai). Thus, the ultrasound beam has to be transferred to a pancreatic damage, resulting in an entire extermination of all required and planned pancreatic cancer cells instead of merely removing the local tumor (Wu). Major benefits of the HIFU therapy include the fact that this treatment seems to be less intrusive with no opening, scission, and cicatrizing (Wu). Moreover, this method is cheaper than other options for treating pancreatic cancer. Furthermore, the patient encounters a lower level of pain, while the recovery time appears to be short. In fact, these benefits lead to an aggregated decline in death rate, morbidities, hospital retention, expenses, as well as an enhanced quality of life for cancer patients (Keane).
Definition of HIFU Abscission
The facts demonstrate that ultrasound stands for a specific type of vibration wave (Keane). This vibration wave can be inclined to a close conjure being distanced from its source, while an ultrasound beam disseminates and spreads innocuously and safely across living tissues (Gao). Similarly to how sun energy can be focused using an augmentative glass at some specific point and utilized for setting fire to inflammable materials, an ultrasound beam power can be concentrated in accordance with the analogous sphere (Wu,). In case there is enough focused energy, it leads to tissue extermination, which appears merely across the nidal content, while overlying and closely situated cells remain intact (Wu).
Absorption of ultrasound energy by the living tissue might lead to moderate increases of the temperature. Concerning the HIFU, the greatest ultrasound energy appears across the nidal content, which presupposes that the temperature will be the highest in this particular point (Zhao).
In fact, the HIFU appliance and mechanism for cell elimination seem to be essentially thermal. Hence, the temperature increases hastily and is kept at the level of above 56 °C for 1 second or even longer (Wu). This provokes instant concretion mortification (necrosis) of the necessary extent. The achieved temperature together with the time length of its application actually determines the extent of the cellular thermal impairment (Zhou). This presupposes that the higher is the temperature, the shorter is the time necessary for production and obtainment of required results and outcomes. The borderline of the thermally mortified location, which is appealed to as “lesion” in regards with energy stands for “56 °C for 1 s or longer” outline (Wu). The facts demonstrate that higher temperature will be attained in the thermally mortified location center, which presupposes that the temperature in the nidal content might elevate instantly above 80 °C during this therapy (Wu). A HIFU lesion boundary has an impetuous temperature incline, while acute differentiation between normal extra-nidal and cured tissues appears to be merely smaller than 10 cells. The whole process is histologically observed with the help of a light microscope (Wu).
Both thermal impacts and effects appearing from mechanical mechanisms are believed to be highly significant in the utilization of high ultrasound intension levels. The most essential non-thermal appliance in regards with the tissue extermination in the HIFU field is acoustic void formation, which results in focal ruination of the tissue because of cavitation-generated high temperatures and pressures. The main purpose of the HIFU therapy is delivery of ultrasound energy to a well-outlined calibrated content in regards with size and depth, together with inducing entire concentration mortification of the tumor. The facts demonstrate that a single (1-3 seconds) HIFU subjection typically results in a small cigar-figured damage with proportions of approximately 10-20 mm alongside the steam axle and 1-2 mm in the transversal course (Wu). Nevertheless, positioning of the lesions in an alongside manner, coinciding with convergent contents of abscission of clinically appropriate dimension and magnitude can be obtained. It is also essential to mention that separate lesions overlay in such order that no vital and living nidal cells remain between these lesions (Miller, Smith, Bailer, Czarnota, Hynynen, & Makin).
Moreover, because of the fact that the HIFU requires using small lesion for treating large tumors and theoretically there should be no restrictions in regards with the tumor size, the procedure will have to be protracted, long-lasting, and expensive, especially when attempting to remove a large tumor (Wu). This is the main reason why the HIFU treatment procedure may be subdivided into two sessions when neoplasm appears to be too immersing in case of elder and weakened patients (Zhou). Moreover, each session removes a separated element of the tumor for the procedure to be safer for the patient’s health and overall state. Nevertheless, due to the fact that the HIFU is directed by either US (Ultrasound) or MRI (Magnetic Resonance Imaging), it appears to be impossible to medicate small tumors (those that are smaller than 0.5 mm), especially when they cannot be distinctly revealed by the two imaging techniques (Wu).
The HIFU has been mainly recognized as a mitigating alternative of treating patients with locally advanced pancreatic cancer (Wu). In fact, there are two HIFU devices accessible for the clinical utilization. Both of them encompass B-manner ultrasonography in order to calibrate and control the therapeutic process (Keane). The first one stands for the extracorporeal ultrasound-directed HIFU appliance, which utilizes incessant HIFU wave with the high intensity level (Sung). The therapeutic regimen of this device usually stands for thermal removal and each patient can obtain this type of medication only once. The medication time depends on the proportion of the calibrated tumor and may vary between 45 minutes and 3 hours (Sung). The acoustic intension should progressively elevate during the procedure until a hyperechoic alteration can be distinctively seen within the calibrated lesion (Sung). The second device also stands for an extracorporeal ultrasound-directed HIFU appliance. Contrary to the first one, it utilizes pulsate-wave HIFU with low intension (Wu). The therapeutic regimen appears to be almost identical to the concentrated ultrasound heat-collapse medication. This method presupposes that each patient has to individually experience 5-7 sessions during the period of 10-14 days (Wang). Each session takes approximately between 1 and 2 hours. This procedure presupposes that acoustic intension has to decline in case a patient experiences ventral ache or nuisance.
Incessant-Wave HIFU Medication
The first favorable outcome of HIFU removal of advanced pancreatic cancer appeared in China in 2000 (Wu). It incorporated phase I-II feasible clinical testing. Clinical testing allowed observing both perdurance advantage and ache monitoring during the follow-up period. The study analyzed how eight patients with locally advanced pancreatic cancer were medicated only once with only the incessant-wave HIFU for mitigation. The diameter of tumors ranged between 4.5 and 8 cm and it was mainly situated in the tail or the body of the pancreas (Wu). The outcomes of this study demonstrated that the HIFU medication appeared to be secure, safe, and realizable. Moreover, the study did not record any complications. Pre-existent solid ache of presumptive cancerous origin dissipated for each patient after the HIFU treatment. In addition, follow-up imaging demonstrated diminution or destitution of tumor vascular supply in medicated locations, together with an essential wastage of the removed tumor. Therefore, the HIFU mediation appears to be secure, efficient, and realizable for the medication of patients who have advanced pancreatic cancer (Wu).
Thereafter, a number of clinical researches and tests have been conducted in order to analyze security and reliability of the HIFU method for medication of patients who have pancreatic cancer of the advanced stage (Wang). These clinical studies have been one-phase I-II tests, which have revealed highly encouraging results. One study has revealed a tentative practice of utilizing the HIFU for six patients with inoperable pancreatic cancer. The contrast-enhanced MR imaging demonstrates entire removal in 5 out of 6 patients after the HIFU treatment (Wang). Moreover, all patients have reported ache mitigation. The study has not observed any local skin burns; however, opening artery blood-clotting has been reported to be the main complication for one patient after the HIFU medication.
Another study has demonstrated treatment of 46 patients with advanced pancreatic cancer, including 18 patients with stage III and 28 patients with the stage IV disease (Sung). The contrast-enhanced MR imaging has showed 90-100 percent removal in regards with 38 lesions, 50-90 percent for 8 and less, and 50 percent for 3 lesions after the HIFU medication (Sung). Nevertheless, the study has demonstrated minor complications, including ventral ache, fever, and vomiting for 28 instances of the HIFU medication. In addition, major complications have appeared in five HIFU medication instances, encompassing 2-3 degree skin burns for two patients, pancreatic duodenal fistula in two instances, and gastrointestinal tract bleeding caused by gastric ulcer for one patient (Sung). Nevertheless, the authors of the study have conducted that this method of medication can be regarded as secure and efficient. It might also entail outstanding and exceptional local tumor monitoring and control for the majority of patients suffering from advanced pancreatic cancer.
Nevertheless, the largest clinical study and experiment of utilizing the HIFU medication for advanced pancreatic cancer has been reported by Wang.
224 patients in total have been enrolled in the research to study security and safety of the HIFU medication. Ten patients have revealed gastrointestinal abnormality in the form of ventral distention and anepithymia combined with mild vomiting after the HIFU medication treatment (Wang). In addition, vertebral damage has been defined by MRI imaging for two patients despite the fact that they did not demonstrate any symptoms. Nevertheless, none of the enrolled patients has revealed any severe or major complications. These outcomes vividly illustrate that the HIFU medication appears to be a safe and secure non-invasive treatment. However, this particular study has not entailed any long-term follow-up or survival data (Wang).
Pulse-Wave HIFU Medication
Contrary to incessant-wave HIFU medication, pulse HIFU typically utilizes decreased energy together with a frequentative-session therapy regimen. One of the studies analyzing pulse HIFU for advanced pancreatic cancer has observed treatment of 15 patients who underwent frequentative-session pulse HIFU therapy in order to mitigate their pain and disease consequences (Miller). This study demonstrates that seven patients revealed a lesion in the pancreas, including patients who had previously undergone internal gall bladder circuitous surgery. Other eight patients suffered from pancreas body and tail carcinoma. After the HIFU, all patients suffering from cancer-connected ache acknowledged absence of pain. Three patients demonstrated shrinking of the tumor size, while the rest of the patients did not experience any significant changes. In addition, the study has not revealed any survival favorable outcome, while medium-scope ventral ache has been registered in the form of sequela for two patients (Miller ). Another study has encompassed 25 patients suffering from unresectable pancreatic cancer (Wang, Gao, & Meng).
The study reveals that 19 patients obtained one-time HIFU treatment, while the rest of subjects had to experience two-session therapies lasting for less than 60 minutes. The research demonstrates that the HIFU therapy caused first-degree skin burns for three patients who later recuperated without any additional treatment. The study has observed activity rise and ache enhancement in 23 patients within the follow-up period (Wang, Gao & Meng). Five patients suffered from medium-degree ventral ache, while hypodermic fat hardening was observed in four instances after the therapy. Moreover, one patient encountered second-degree skin burns together with pancreatic outflow. The study has not revealed any significant ache mitigation and survival information (Wang, Gao & Meng,). The researches have also analyzed the combination of pulse HIFU treatment with chemotherapy for medicating advanced pancreatic cancer. The researches show that numerous patients suffer from second-degree and first-degree skin burns (Wu). Moreover, thermal damage can rarely provoke hypodermic fat sclerosis together with sharp pancreatitis causing large-scale pseudocyst (Wu). Therefore, these data demonstrate that that a combination of pulse HIFU and chemotherapy might be much more efficient for treatment of unresectable pancreatic cancer than the advanced one.
The paper shows that the HIFU treatment appears to be a compelling and appealing protruding treatment of the non-resectable pancreatic cancer. Primarily, this method has been suggested for use in the form of a mitigating and palliation alternative as it helps to increase the quality of life for patients who suffer from advanced-stage pancreatic cancer. The majority of researches and studies reveal that the HIFU treatment is secure, safe, and helpful in treating pancreatic cancer. Therefore, the HIFU approach of removing tumors appears to be a promising method for the alleviating therapy of advanced pancreatic cancer. Non-invasive character of this approach, which is combined with high accuracy of the therapy, makes the HIFU a highly appealing treatment method. All preliminary researches and studies demonstrate that this method is technically secure and attainable and might be utilized both alone and in combination with systematic chemotherapy. This method efficiently alleviates cancer-connected ventral ache and helps in conferring an additional survival favorable outcome, while showing a limited number of complications.