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OBJECTIVES: Pancreatic cancer patients often have a high symptom burden, significantly impairing patients' quality of life (QOL). Nevertheless, there are hardly any reports on the impact of high-intensity focused ultrasound (HIFU) on the QOL of treated patients. For the first time, this study evaluated the effect of HIFU on QOL and compared these results in two European centers. METHODS: Eighty patients with advanced pancreatic cancer underwent HIFU (50 in Germany, 30 in Bulgaria). Clinical assessment included evaluation of QOL and symptoms using the EORTC QLQ-C30 questionnaire at baseline and 1, 3, and 6 months after HIFU. Pain intensity was additionally evaluated with the numerical rating score (NRS). RESULTS: Compared to baseline, global health significantly improved 3 and 6 months after HIFU treatment (p = 0.02). Functional subscales including physical, emotional, and social functioning were considerably improved at 6 months (p = 0.02, p = 0.01, and p = 0.01, respectively) as were leading symptom pain (p = 0.04 at 6 months), fatigue (p = 0.03 at 3 and p = 0.01 at 6 months), and appetite loss (p = 0.01 at 6 months). Moreover, pain intensity measured by NRS revealed effective and strong pain relief at all time points (p < 0.001). Reported effects were independent of tumor stage, metastatic status, and country of treatment. CONCLUSIONS: This study showed that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL by increasing global health and mitigation of physical complaints with a low rate of side effects, independent of the examiner. Therefore, HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease. KEY POINTS: ⢠In a prospective two-center study, it was shown that HIFU represents an effective treatment option of advanced pancreatic cancer improving QOL. ⢠HIFU in pancreatic cancer patients is associated with a low rate of side effects, independent of the performer. ⢠HIFU is a worthwhile additional treatment besides systemic palliative chemotherapy or best supportive care in management of this aggressive disease.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias Pancreáticas , Alemanha , Humanos , Neoplasias Pancreáticas/terapia , Estudos Prospectivos , Qualidade de VidaRESUMO
INTRODUCTION: High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. MATERIAL AND METHODS: A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. RESULTS: An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p < .001) for both tumor entities demonstrating effective treatment outcome. CONCLUSION: Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.
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Neoplasias Abdominais , Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias Uterinas , Feminino , Alemanha , Humanos , Inflamação/diagnóstico por imagem , Laboratórios , Resultado do TratamentoRESUMO
INTRODUCTION: To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. MATERIALS AND METHODS: Uterine fibroids treated by USgHIFU were assigned to Funaki type 1-3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland-Altman's plot and Spearman's correlation. RESULTS: In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p < .05). Moreover, patients experienced a significant improvement of fibroid-associated hypermenorrhea (3.9 ± 1.3 vs. 2.3 ± 1.3), pressure in the pelvic area (3.5 ± 1.3 vs. 2.1 ± 0.9) and frequent urination (2.8 ± 1.5 vs. 1.9 ± 0.8) one year post-procedure (each p < .05), regardless of fibroid Funaki type. CONCLUSION: Following USgHIFU, a significant shrinkage of uterine fibroids and improvement of leading fibroid-associated symptoms were demonstrated regardless of the Funaki type.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Neoplasias Uterinas , Feminino , Humanos , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Imageamento por Ressonância Magnética , Estudos Prospectivos , Resultado do Tratamento , Ultrassonografia de Intervenção , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgiaRESUMO
Introduction: High-intensity focused ultrasound (HIFU) for pancreatic cancer is a growing therapeutic field which has been proven to reduce cancer pain and provide a local tumor control additionally to standard palliative care. However, less is known about the multidisciplinary and especially anesthesiological management of HIFU treatment although an interdisciplinary approach is crucial for treatment success.Material and methods: Anesthesiological and radiological records of 71 HIFU-treated pancreatic cancer patients were analyzed with regard to the following items: intervention time, sonication time, total energy, anesthesia time, peri-interventional medication, body temperature maximum and minimum, pain scores before and 1 day, 6 weeks and 3 months after intervention, peri-interventional complications. Effects on pain scores were estimated with a mixed panel data model. Bivariate associations between interventional variables were examined with the Spearman's correlation.Results: HIFU treatment was performed without major adverse events. Peri-procedural hyperthermia >37.5 °C occurred in 2 patients, hypothermia <35 °C in 8 cases. Interventional variables did not correlate significantly with pain scores, opioid dose, nor body temperature. 85.5% of patients experienced significant early pain relief within the first week after intervention. Post-interventional pain relief is associated with morphine equivalent opioid dose (p = 0.025) and treatment time (p = 0.040).Conclusion: While HIFU can be considered safe and effective treatment option, procedure-associated pain and temperature management represent challenges for the interdisciplinary HIFU intervention team. Especially short-term pain relief depends on the combined effort of the radiologist and anesthesiologist.
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Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Neoplasias Pancreáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Resultado do TratamentoRESUMO
Aim of the study was to evaluate the diagnostic performance and feasibility of transabdominal ultrasound shear wave elastography (SWE) in assessing sonoelastographic features of the uterus. Twenty-seven premenopausal women were enrolled between 2021 and 2022. Transabdominal SWE measured myometrial stiffness in various uterine segments. Additionally, tissue stiffness of the quadriceps femoris muscle and autochthonous back muscle was measured. Statistical analysis employed non-parametric tests, t test, and a robust mixed linear model. Stiffness values of the uterus and the two investigated muscle types exhibited a similar spectrum: 6.38 ± 2.59 kPa (median 5.61 kPa; range 2.76-11.31 kPa) for the uterine myometrium, 7.22 ± 1.24 kPa (6.82 kPa; 5.11-9.39 kPa) for the quadriceps femoris musle, and 7.43 ± 2.73 kPa (7.41 kPa; 3.10-13.73 kPa) for the autochthonous back muscle. A tendency for significant differences in myometrial stiffness was observed concerning the type of labor mode (mean stiffness of 9.17 ± 1.35 kPa after vaginal birth vs. 3.83 ± 1.35 kPa after Caesarian section, p = 0.01). No significant differences in myometrial stiffness were observed concerning age, BMI, previous pregnancies, uterine flexion and menstrual cycle phase. Transabdominal SWE of uterine stiffness seems to be a fast and practicable method in a clinical setting. Uterine stiffness appears to be largely independent of various factors, except for the mode of delivery. However, further studies are needed to validate these results.
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Técnicas de Imagem por Elasticidade , Útero , Humanos , Feminino , Técnicas de Imagem por Elasticidade/métodos , Adulto , Útero/diagnóstico por imagem , Miométrio/diagnóstico por imagem , Gravidez , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: High-intensity focused ultrasound (HIFU) is used for the treatment of symptomatic leiomyomas. We aim to automate uterine volumetry for tracking changes after therapy with a 3D deep learning approach. METHODS: A 3D nnU-Net model in the default setting and in a modified version including convolutional block attention modules (CBAMs) was developed on 3D T2-weighted MRI scans. Uterine segmentation was performed in 44 patients with routine pelvic MRI (standard group) and 56 patients with uterine fibroids undergoing ultrasound-guided HIFU therapy (HIFU group). Here, preHIFU scans (n = 56), postHIFU imaging maximum one day after HIFU (n = 54), and the last available follow-up examination (n = 53, days after HIFU: 420 ± 377) were included. The training was performed on 80% of the data with fivefold cross-validation. The remaining data were used as a hold-out test set. Ground truth was generated by a board-certified radiologist and a radiology resident. For the assessment of inter-reader agreement, all preHIFU examinations were segmented independently by both. RESULTS: High segmentation performance was already observed for the default 3D nnU-Net (mean Dice score = 0.95 ± 0.05) on the validation sets. Since the CBAM nnU-Net showed no significant benefit, the less complex default model was applied to the hold-out test set, which resulted in accurate uterus segmentation (Dice scores: standard group 0.92 ± 0.07; HIFU group 0.96 ± 0.02), which was comparable to the agreement between the two readers. CONCLUSIONS: This study presents a method for automatic uterus segmentation which allows a fast and consistent assessment of uterine volume. Therefore, this method could be used in the clinical setting for objective assessment of therapeutic response to HIFU therapy.
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Uterine fibroids are the most common benign tumors of the uterus. Approximately 20-50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.
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Uterine fibroids are the most common benign uterine tumors and can cause various severe symptoms as abnormal menstrual bleeding or pelvic pain. Therefore, the primary objective in the treatment of uterine fibroids is a sufficient symptom relief. Ultrasound (US)-guided High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment strategy for ablation of uterine fibroids that can achieve a significant tumor volume reduction. The aim of the study is to evaluate if US-guided HIFU treatment can reduce fibroid-associated symptoms leading to an improvement of health-related quality of life. Fifty-five women with symptomatic uterine fibroids underwent US-guided HIFU ablation. Clinical evaluation was performed on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) at baseline, 6 weeks, 3, 6, 9 and 12 months after HIFU. Imaging follow-up included contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI. A significant reduction of the Symptom Severity Scale (SSS) was observed between 6 weeks and 12 months after HIFU (49.9 ± 19.4 at baseline vs. 42.2 ± 20.1 at 6 weeks and 23.6 ± 12.7 at 12 months after treatment, p < 0.001) correlating with a significant improvement (p < 0.001) of Health-related Quality of Life (HRQL) (52.5 ± 22.7 at baseline vs. 59.8 ± 22 at 6 weeks and 77.9 ± 17.3 at 12 months after treatment). Significant postinterventional improvement was observed in every subscale of HRQL. In the majority of patients, only minor, short-lasting and self-limiting side effects were observed, e.g. soft tissue edema of the anterior lower abdominal wall in the acoustic pathway or transient moderate lower abdominal pain as during menstruation. One patient with a very large fibroid experienced strong short-lasting pain after the procedure; two patients experienced post-procedurally a transient sciatic nerve irritation. US-guided HIFU of uterine fibroids reduces disease-related symptoms and improves health-related quality of life.
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Leiomioma , Qualidade de Vida , Humanos , Feminino , Acústica , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgiaRESUMO
Little is known about the specific anaesthesiological and multidisciplinary management of high-intensity focused ultrasound (HIFU) in uterine fibroids. This observational single-center study is the first reporting on an interdisciplinary approach to optimize outcome following ultrasound (US)-guided HIFU in German-speaking countries. A sample of forty patients with symptomatic uterine fibroids was treated by HIFU. Relevant treatment parameters such as total treatment time for intervention, anaesthesia, and sonication time as well as total energy, body temperature, peri-interventional medication and complications were analyzed. Interventional variables did not correlate significantly either with opioid dose or with body temperature. The average fibroid volume reduction rate was 37.8% ± 23.5%, 48.5% ± 22.0% and 70.2% ± 25.5% after 3, 6 and 12 months, respectively. No major anaesthesiological complications occurred apart from an epileptic seizure prior to HIFU treatment in one patient. Peri-procedural hyperthermia (> 37.5 °C) occurred in two patients. Post-procedural two patients experienced a sciatic nerve irritation up to one year; one patient with very large treated fibroid experienced strong short-lasting post-procedural pain. There were two complication-free pregnancies of HIFU-treated patients. Multidisciplinary management is crucial to optimize safety and outcome of US-guided HIFU for uterine fibroids. Peri-procedural pain and temperature management are critical points where an adequate collaboration between anesthesiologist and interventionalist is mandatory.
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Ablação por Ultrassom Focalizado de Alta Intensidade/normas , Leiomioma/cirurgia , Equipe de Assistência ao Paciente/normas , Neoplasias Uterinas/cirurgia , Adulto , Gerenciamento Clínico , Feminino , Humanos , Leiomioma/patologia , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND: Thanks to modern multimodal treatment the ouctome of patients with colorectal cancer has experienced significant improvements. As a downside, agent specific side effects have been observed such as sinusoidal obstruction syndrome (SOS) after oxaliplatin chemotherapy (OX). Bevazicumab targeting VEGF is nowadays comprehensively used in combination protocols with OX but its impact on hepatotoxicity is thus far elusive and focus of the present study. RESULTS: After MCT administration 67% of animals developed SOS. GOT serum concentration significantly increased in animals developing SOS (p < 0.001). Subsequent to MCT administration 100% of animals treated with Anti-VEGF developed SOS. In contrast, animals receiving VEGF developed SOS merely in 40% while increasing the VEGF dose led to a further decrease in SOS development to 25%. MMP 9 concentration in animals developing SOS was significantly higher compared to controls (p < 0,001). Additional treatment with Anti-VEGF increased the MMP 9 concentration significantly (p < 0,05). CONCLUSIONS: Preservation of liver function is a central goal in both curative and palliative treatment phases of patients with CRC. Thus, knowledge about hepatotoxic side effects of chemotherapeutic and biological agents is crucial. From the results it can be concluded that Anti-VEGF exacerbates SOS paralleled by MMP 9 production. Therefore, OX-Bevacizumab combination therapies should be administered with caution, especially if liver parenchyma damage is apparent. METHODS: Male Sprague-Dawley rats were gavaged Monocrotaline (MCT) to induce SOS. Recombinant VEGF or an Anti-VEGF antibody was administered to MCT-treated rats and the hepatotoxic effect monitored in defined time intervals. MMP 9 expression in the liver was measured by ELISA.