Objective To evaluate the safety and efficacy of high intensity focused ultrasound for palliation of inoperable pancreatic cancer in humans. Patients Eighty-nine patients with advanced pancreatic cancer were treated with high intensity focused ultrasound. Methods Pain relief, local tumor control rate, median survival and complications were observed after high intensity focused ultrasound treatment. Pain relief was achieved in The median survival was
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There were no severe complications in patients undergoing HIFU treatment. However, patients experienced significantly increased toxicity compared to GEM alone. Besides chemotherapy, minimally invasive ablative therapies are another option for patients with unresectable PDAC who cannot undergo curative surgery and have a limited response to systemic chemotherapy.
All the patients were abstracted to an anonymized database and were analyzed retrospectively for baseline demographics, tumor characteristics, treatment details, and outcomes as documented in the medical records. The diagnosis of PDAC was histologically or cytologically confirmed. All patients were informed of the potential benefits and risks of HIFU therapy. HIFU therapy was administered before chemotherapy.
Patients were instructed to fast for 12 hours before HIFU therapy. The following parameters for the therapeutic US transducer were used: 1 frequency: 0. Real-time US was used to target the pancreatic tumor by moving the integrated probe, and the tumor was divided into slices with 5 mm separation by using US images.
Blood pressure, pulse, respiration rate, and peripheral oxygenation were monitored during the HIFU treatment. Angiography of the abdominal cavity artery and other target arteries of the cancer was used to determine the location, infringing range, and blood supply of the carcinoma.
Next, a catheter was inserted into the target through the femoral artery. The incidence of HIFU-related adverse events AEs , including burns, abdominal pain, pancreatitis, jaundice, hemorrhage, gastrointestinal GI perforation, and intestinal necrosis, as reported in previous studies, was recorded. Serum amylase and urinary amylase levels were tested the next day after treatment. Quality of life was assessed by the European Organization for Research and Treatment of Cancer quality of life questionnaire core The European Organization for Research and Treatment of Cancer quality of life questionnaire core 30 encompasses 30 items.
It incorporates five items which entail body function, role function, emotion function, and society function. Besides, it also evaluates the existence of fatigue, pain, nausea, and vomiting. Dyspnea, insomnia, loss of appetite, constipation, diarrhea, and economic difficulty are the aspects that need to be considered.
The ultimate score ranges from 0 to The function-associated score is in positive proportion to the well-being of the patient. Moreover, we assessed pain relief among these pancreatic patients. The degree of pain was evaluated by a numerical rating score, as depicted in the universally acknowledged brief pain inventory.
The score ranges from 0 to 10; 0 refers to no pain at all and 10 refers to unbearable pain. The OS was defined as the time from the date of pathologically confirmed diagnosis to the date of the last follow-up or the date of death. Censoring occurred if patients were still alive at the last follow-up or died of other causes.
All statistical analyses were conducted using SPSS OS was calculated according to Kaplan—Meier analysis, and P -values were evaluated by the log-rank test for censored survival data. By scanning with a continuous HIFU beam and sweeping from the deep to the shallow regions of the tumor, the targeted regions in each slice of the tumor were completely ablated. US image obtained immediately after HIFU treatment showed obvious hyperechogenicity of the treated pancreatic tumor Figure 1.
B US image obtained immediately after HIFU treatment showing obvious hyperechogenicity of the treated pancreatic tumor red arrow. The average age in the combined therapy group and the GEM monotherapy group was The male-to-female ratios were 1. Of the combined therapy patients, 26 7. In the GEM monotherapy group, 22 Seventy-nine Chi-squared tests showed no differences between the two groups with respect to age, sex, and stage, but there was a difference with respect to tumor location.
Table 2 Baseline characteristics of patients in the combined therapy group. Among patients in the cohort of combined therapy, a total of had liver metastasis and 42 had lung metastasis.
Also, 56 patients had bone metastasis and the number of patients who had metastasis to peritoneum and lymph node was 36 and 23, respectively. In the gemcitabine-only group, the number of patients with metastasis to liver, lung, bone, peritoneum and lymph node was 93, 21, 34, 29, and 17, respectively. The 6-month, month, 1-year, and 2-year survival rates for patients in these two groups were Figure 2 The median OS in the combined therapy group green line and the gemcitabine monotherapy group blue line : 7.
Abbreviation: OS, overall survival. Overall, AEs occurred in 27 7. Skin burns did occur in four patients, among whom one had deep second-degree burns. Vertebral injury, identified by MRI, occurred in two patients, although no symptoms were observed. Abdomen and waist pain occurred in two cases and gradually subsided within 1 week of a rectal indomethacin suppository.
Obstructive jaundice concomitant with biliary tract infection developed in one case, in which a tumor was located on the head of the pancreas; percutaneous transhepatic cholangial drainage and anti-infective therapy were administered and showed good therapeutic efficacy.
The serum amylase levels were increased in 13 cases 7. Since all of them were diagnosed by black stool and positivity for fecal occult blood, hemostatic treatment was given. Besides, we observed that the quality of life had improved and pain was reduced by HIFU treatment. Table 3 Adverse events in the combined therapy group Abbreviation: GI, gastrointestinal.
A slight increase in tumor volume arrowhead could be observed in some of the PDAC patients after some consecutive chemotherapy. However, these lesions showed a decrease in tumor size and the amount of soft tumor tissue arrowhead encasing the celiac artery after some sessions of HIFU therapy concurrent with some additional sessions of chemotherapy, as shown in Figure 4. Figure 4 A year-old man was diagnosed with unresectable pancreatic cancer on October 28, Notes: A A contrast-enhanced CT image October 28, showed a mass on the neck of the pancreas arrowheads.
B A contrast-enhanced CT image January 28, taken after three consecutive chemotherapy sessions showed a slight increase in tumor volume arrowheads.
C A contrast-enhanced CT image August 11, taken after an additional two sessions of concurrent chemotherapy and a single session of HIFU therapy showed a decrease in tumor size and the amount of soft tumor tissue arrowheads encasing the celiac artery, but progression of the disease occurred with liver metastasis.
However, there was no statistical difference in the long-term survival no less than 2 years between these two groups.
However, the effects of these chemotherapies are limited. In this study, we enrolled patients subject to GEM monotherapy, considering their performance status PS and their disease stage.
The estimated median OS was We suggest that the difference could be ascribed to the difference in HIFU equipment applied in the treatment. In order to evaluate the role of age and tumor location on the survival of these pancreatic patients, we detected their effects not only on the entire cohort of patients, but also on the combined group and the gemcitabine-only group.
Results have shown that age was an independent prognostic factor in the subgroups of these PDAC patients. Primary tumor location was also a prognostic factor affecting OS.
However, as a retrospective study, this is a deficiency which could not be totally avoided. HIFU combined with RIAC and systemic chemotherapy strategy group C has been first reported in the present study, which showed significant survival benefits than the other two groups. Some studies presumed that the mostly mechanistic rationale may be based on two aspects: 1 the hyperthermia caused by pulsed HIFU induces an increase in blood flow to pancreatic mass, which may increase the drug delivery and 2 HIFU can induce structural and molecular changes due to cavitation damage, shear stress, and micro-streaming, all of which may enhance drug extravasations and sensitize the cancer cells.
In terms of safety, high-intensity US beams may produce burns in the tissues that lie between the transducer and the target area. Thermal injury could occur at either the shallower areas of the target lesion or due to unwanted deep penetration through the target area. Skin burns did occur in four patients. Among these patients, one developed deep second-degree burns and recovered automatically 4 weeks later.
Vertebral injuries were observed in two cases, and bone-related AEs did not occur in these two patients. HIFU entails the risk of biliary perforation or biliary duct damage that can result in malignant biliary obstruction by thermal injury when cancers are located in the head of the pancreas. One patient with a lesion in this location suffered from biliary obstruction accompanied by acute infection of the biliary tract.
After receiving percutaneous transhepatic cholangial drainage combined with anti-infection therapy, the patient showed complete recovery. Therefore, HIFU should be performed with caution in patients with pancreatic head cancer and body masses, as it is potentially detrimental to the invaded biliary and digestive tracts since these critical structures cannot be avoided when directing the travel path of HIFU beams. However, it cannot prolong the long-term survival no less than 2 years and more studies are needed to explore the association between HIFU and drug.
Despite a lack of randomization and potential selective bias, the outcomes of HIFU combined with GEM in the present study are highly encouraging, and should be an impetus for further studies and hopefully be applied more in clinical practice. Pulsed high-intensity focused ultrasound enhances apoptosis of pancreatic cancer xenograft with gemcitabine.
Ultrasound Med Biol. Intensity modulated radiotherapy for locally advanced and metastatic pancreatic cancer: a mono-institutional retrospective analysis. Radiat Oncol. High-intensity focused ultrasound treatment of late-stage pancreatic body carcinoma: optimal tumor depth for safe ablation. Zhou Y. High-intensity focused ultrasound treatment for advanced pancreatic cancer. Gastroenterol Res Pract. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement by Callery et al.
JEAN AUEL PLAINS PASSAGE PDF
A meta-analysis of palliative treatment of pancreatic cancer with high intensity focused ultrasound
Pancreatic cancer is under high mortality but has few effective treatment modalities. High-intensity focused ultrasound HIFU is becoming an emerging approach of noninvasively ablating solid tumor in clinics. A variety of solid tumors have been tried on thousands of patients in the last fifteen years with great success. The principle, mechanism, and clinical outcome of HIFU were introduced first.
THIRUMOOLAR YOGA PDF
HIFU for Palliative Treatment of Pancreatic Cancer
Current therapies are ineffective, and the treatment of patients with advanced disease is palliative. In the past decade, HIFU ablation has emerged as a modality for palliative treatment of pancreatic tumors. Multiple preclinical and non-randomized clinical trials have been performed to evaluate the safety and efficacy of this procedure. Substantial tumor-related pain reduction was achieved in most cases after HIFU treatment and few significant side effects were observed. In addition, some studies indicate that combination of HIFU ablation with chemotherapy may provide a survival benefit. This chapter summarizes the pre-clinical and clinical experience obtained to date in HIFU treatment of pancreatic tumors and discusses the challenges, limitations and new approaches in this modality.
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