Study Protocol of a Prospective, Monocentric, Single-Arm Study Investigating the Safety and Efficacy of Local Ablation of Symptomatic Uterine Fibroids with US-Guided High-Intensity Focused Ultrasound (HIFU).

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.

Improvement of fibroid-associated symptoms and quality of life after US-guided high-intensity focused ultrasound (HIFU) of uterine fibroids.

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.

Improving quality of life in pancreatic cancer patients following high-intensity focused ultrasound (HIFU) in two European centers.

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.

Mesenteric Vessel Patency Following HIFU Therapy in Patients with Locally Invasive Pancreatic Cancer.

PURPOSE: To evaluate the effects of HIFU therapy on visceral vessel patency in patients with inoperable locally invasive pancreatic cancer. MATERIALS AND METHODS: 50 pancreatic cancer patients (26 men, 24 women) aged 41 - 82 years (65.0 ±â€Š10.2) underwent ultrasonography (US) and computed tomography (CT) examinations before and within one day after HIFU treatment, as well as at follow-up at six weeks, three months and six months. Evaluation and grading were performed by two experienced independent radiologists according to a classification scheme based on vessel involvement, vessel diameter, patency, and defects in flow. RESULTS: Before HIFU treatment, arterial vessel involvement was noted in 42 patients, venous involvement in 47, and 47 patients presented with both. Superior mesenteric artery occlusion was found in three carcinomas while nearly half of the cases (n = 24) displayed signs of superior mesenteric vein, portal vein, or splenic vein occlusion. High-grade tumor-associated arterial narrowing was seen in ten patients. Despite vessel encasement and partially extensive propagation of collateral vessels, it was possible to safely perform HIFU treatment in all patients without complications. US and CT studies performed within one day after therapy did not show any change in vessel patency in 47 patients (94 %). Follow-up controls at the six-week mark revealed increased vessel narrowing and finally occlusion after six months in 11 patients due to tumor progression. CONCLUSION: This study demonstrates that HIFU treatment can be safely applied to pancreatic cancers enveloping large mesenteric vessels despite vessel narrowing or extensive collateral propagation. Most patients (94 %) did not experience adverse effects regarding vessel patency.

High-intensity focused ultrasound (HIFU) for pancreatic carcinoma: evaluation of feasibility, reduction of tumour volume and pain intensity.

OBJECTIVES: Prognosis of patients with locally advanced pancreatic adenocarcinoma is extremely poor. They often suffer from cancer-related pain reducing their quality of life. This prospective observational study aimed to evaluate feasibility, local tumour response, and changes in quality of life and symptoms in Caucasian patients with locally advanced pancreatic cancer treated by ultrasound-guided high-intensity focused ultrasound (HIFU). METHODS: Thirteen patients underwent HIFU, five with stage III, eight with stage IV UICC disease. Ten patients received simultaneous palliative chemotherapy. Postinterventional clinical assessment included evaluation of quality of life and symptom changes using standardized questionnaires. CT and MRI follow-up evaluated the local tumour response. RESULTS: HIFU was successfully performed in all patients. Average tumour reduction was 34.2 % at 6 weeks and 63.9 % at 3 months. Complete or partial relief of cancer-related pain was achieved in 10 patients (77 %), five of whom required less analgesics for pain control. Quality of life was improved revealing increased global health status and alleviated symptoms. HIFU treatment was well tolerated. Eight patients experienced transient abdominal pain directly after HIFU. CONCLUSIONS: HIFU ablation of pancreatic carcinoma is a feasible, safe and effective treatment with a crucial benefit in terms of reduction of tumour volume and pain intensity. KEY POINTS: • US-guided HIFU is feasible and safe for patients with unresectable pancreatic cancer. • HIFU can considerably reduce tumour volume and cancer-related pain. • Patients treated with HIFU experienced significant and lasting reduction of pain intensity. • HIFU has a crucial clinical benefit for patients with pancreatic cancer.

Use of routine thoracic and abdominal computed tomography scans for assessing bone mineral density and detecting osteoporosis.

OBJECTIVE: Evaluation of computed tomography (CT) attenuation measurements for assessing bone mineral density (BMD) and predicting osteoporosis in thoracic and abdominal CT scans for various clinical indications using dual-energy X-ray absorptiometry (DXA) as reference standard. RESEARCH DESIGN AND METHODS: A total of 234 patients (147 women, 87 men) undergoing DXA and CT were examined retrospectively. Mean time between both studies was 0.5 years. CT-attenuation values in Hounsfield units (HU) were measured at the thoracic and lumbar spine (T1, T6, T12, L1-L5), at the femoral neck, and then assigned to their corresponding DXA scores. RESULTS: Patients with DXA-defined osteoporosis or osteopenia showed significantly lower HU values of trabecular bone at all measured levels compared to healthy subjects (p < 0.001). HU values were highest at T1 and T6, lowest at L1-L3 and the femoral neck. There were no significant intraindividual differences between HU values in the sagittal, coronal or transversal plane. Significant differences between normal and abnormal BMD categories were verified for three CT scanners. More than half of all fractures were detected in patients with non-osteoporotic DXA T-scores. CONCLUSIONS: Abdominal and particularly thoracic CT scans obtained for other clinical indications can sensibly be applied toward determining low BMD, detecting osteoporosis and identifying persons at increased fracture risk. Osteoporotic morbidity and mortality might be minimized. Superiorly to DXA, fragility fractures can be found without additional imaging or radiation exposure which can initiate early adequate treatment. LIMITATIONS: Key limitations of the study were as following: a retrospective, single-center study; small patient cohort - larger cohorts are needed to evaluate the sensitivity and specificity of diagnostic performance measurements; more complex CT evaluation of the hip for BMD assessment; DXA measurements were used as a reference standard, however, patients with unsuspected compression fractures but showing osteopenic or even normal BMD outline the limitations of DXA.

CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt.

BACKGROUND & AIMS: Inflammation, collagen deposition and tissue remodelling are involved in the pathogenesis and complications of cirrhosis with portal hypertension. CXCL9 and other chemokines play an important role in these processes and have been associated with liver injury and complications of liver disease in humans. However, their predictive value in patients with cirrhosis and portal hypertension remains to be established. METHODS: 103 patients with liver cirrhosis who had received TIPS (transjugular intrahepatic portosystemic shunt) were included into this study. The TIPS indication was either refractory ascites or recurrent bleeding. Before and after the TIPS procedure portal and hepatic venous blood samples were obtained in 78 patients. In 25 patients blood samples were obtained from the portal vein, hepatic vein, right atrium and cubital vein at TIPS insertion. Serum levels of CXCL9 were measured by cytometric bead array and correlated with clinical parameters and overall outcome. RESULTS: Portal venous levels of CXCL9 decreased after TIPS. Child-Pugh score, refractory ascites, renal dysfunction and alcoholic aetiology of cirrhosis were associated with increased CXCL9 levels. Importantly, low levels of CXCL9 in portal and hepatic vein samples were prognostic factors for the survival of patients receiving TIPS during long-time follow-up. CONCLUSIONS: The CXCR3 ligand CXCL9 affects the liver and/or is released by the liver and thereby might contribute to hepatic and extrahepatic organ dysfunction. Elevated levels of CXCL9 are associated with shorter survival in cirrhotic patients with severe portal hypertension receiving TIPS. This chemokine should be further evaluated as a novel biomarker for the outcome in patients with cirrhosis and portal hypertension and its modulation as a new therapeutic strategy.

Soluble TNF-alpha-receptors I are prognostic markers in TIPS-treated patients with cirrhosis and portal hypertension.

BACKGROUND: TNFα levels are increased in liver cirrhosis even in the absence of infection, most likely owing to a continuous endotoxin influx into the portal blood. Soluble TNFα receptors (sTNFR type I and II) reflect release of the short-lived TNFα, because they are cleaved from the cells after binding of TNFα. The aims were to investigate the circulating levels of soluble TNFR-I and -II in cirrhotic patients receiving TIPS. METHODS: Forty-nine patients with liver cirrhosis and portal hypertension (12 viral, 37 alcoholic) received TIPS for prevention of re-bleeding (n = 14), therapy-refractory ascites (n = 20), or both (n = 15). Portal and hepatic venous blood was drawn in these patients during the TIPS procedure and during the control catheterization two weeks later. sTNFR-I and sTNFR-II were measured by ELISA, correlated to clinical and biochemical characteristics. RESULTS: Before TIPS insertion, sTNFR-II levels were lower in portal venous blood than in the hepatic venous blood, as well as in portal venous blood after TIPS insertion. No significant differences were measured in sTNFR-I levels. Hepatic venous levels of sTNFR-I above 4.5 ng/mL (p = 0.036) and sTNFR-II above 7 ng/mL (p = 0.05) after TIPS insertion were associated with decreased survival. A multivariate Cox-regression survival analysis identified the hepatic venous levels of sTNFR-I (p = 0.004) two weeks after TIPS, and Child score (p = 0.002) as independent predictors of mortality, while MELD-score was not. CONCLUSION: Hepatic venous levels of sTNFR-I after TIPS insertion may predict mortality in patients with severe portal hypertension.

Embolization of varicocles: pretreatment sperm motility predicts later pregnancy in partners of infertile men.

PURPOSE: To identify predictors of future pregnancy in partners of infertile men undergoing embolization of varicoceles. MATERIALS AND METHODS: This study was conducted within local institutional review board guidelines, and written informed consent was obtained. In 223 clinically infertile men (age range, 18-50 years) with varicoceles and associated oligoteratoasthenospermia, endovascular embolization of the spermatic veins was performed with distal coil embolization and sclerotherapy. Additional anti-inflammatory treatment was initiated if required. Baseline clinical examination, semen specimen, and hormone level findings were compared to follow-up data. Posttreatment pregnancy rate of their healthy female partners was assessed with a standardized questionnaire. Unconditioned logistic regression was used to identify factors among all available clinical and laboratory data predicting treatment success (sired pregnancy during follow-up). RESULTS: A total of 226 of 228 varicoceles in 223 patients were successfully treated. Resolution of varicoceles at clinical examination and ultrasonography (US) was observed in 206 patients (92.4%). Three-month follow-up semen analysis in these patients showed significant improvement in sperm motility (P < .001) and sperm count (P < .001); however, average values remained in the abnormal range (World Health Organization guidelines). In 173 patients, follow-up data were successfully obtained, with pregnancy reported in 45 (26%). Baseline sperm motility was identified as the only significant pretreatment factor (standardized regression coefficient beta = 3.285, t = 7.560, P = .006) predicting sired pregnancy. Hormone levels, clinical grading of varicoceles, Doppler US findings, and other semen parameters did not reach statistical significance. CONCLUSION: Sperm motility prior to varicocele treatment in infertile men is an important predictor of later pregnancy.

Actual clinical use of gadolinium-chelates for non-MRI applications.

For many years, alternatives to iodinated X-ray contrast media have been sought. Of the contrast media investigated to date, only CO(2) and the gadolinium-chelates have been shown to be viable alternatives for selected X-ray examinations. Therefore, we have reviewed the general literature and that specific for gadopentetate (Magnevist) in particular, since this agent has been studied the most. This review indicates that diagnostic CT examinations can be achieved following the intravenous administration of gadolinium-containing contrast media (CM) for evaluation of aortic abnormalities. Gadolinium-containing CM at the dose approved for MR imaging are not useful for CT evaluation of the abdominal parenchymal organs. Intravenous/intraarterial injections have also been used in a variety of angiographic and interventional procedures. Image quality, however, is generally inferior to iodinated contrast media. Gadolinium-containing CM require no special handling and can be administered by hand injection or via conventional angiographic automated injectors with the same flow rates and pressures as are used with iodinated contrast media. For CT, a peripheral bolus injection of a diluted gadolinium agent (1:1 with saline) of 60-90 ml at 3-5 ml/s is usually performed. Similar to all other gadolinium-chelates, the non-MRI use of gadopentetate (Magnevist) is not approved by regulatory agencies. However, the literature suggests that a dose of 0.3-0.4 mmol/kg b.w. has been safely administered for CT as well as for angiography and interventional procedures intravenously and intraarterially. Even at this dose, though, this results in a relatively small overall volume to be injected, which limits utility somewhat.