A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design.

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Risk of cancer incidence before the age of 15 years after exposure to ionising radiation from computed tomography: results from a German cohort study.

The aim of this cohort study was to assess the risk of developing cancer, specifically leukaemia, tumours of the central nervous system and lymphoma, before the age of 15 years in children previously exposed to computed tomography (CT) in Germany. Data for children with at least one CT between 1980 and 2010 were abstracted from 20 hospitals. Cancer cases occurring between 1980 and 2010 were identified by stochastic linkage with the German Childhood Cancer Registry (GCCR). For all cases and a sample of non-cases, radiology reports were reviewed to assess the underlying medical conditions at time of the CT. Cases were only included if diagnosis occurred at least 2 years after the first CT and no signs of cancer were recorded in the radiology reports. Standardised incidence ratios (SIR) using incidence rates from the general population were estimated. The cohort included information on 71,073 CT examinations in 44,584 children contributing 161,407 person-years at risk with 46 cases initially identified through linkage with the GCCR. Seven cases had to be excluded due to signs possibly suggestive of cancer at the time of first CT. Overall, more cancer cases were observed (O) than expected (E), but this was mainly driven by unexpected and possibly biased results for lymphomas. For leukaemia, the SIR (SIR = O/E) was 1.72 (95 % CI 0.89-3.01, O = 12), and for CNS tumours, the SIR was 1.35 (95 % CI 0.54-2.78, O = 7). Despite careful examination of the medical information, confounding by indication or reverse causation cannot be ruled out completely and may explain parts of the excess. Furthermore, the CT exposure may have been underestimated as only data from the participating clinics were available. This should be taken into account when interpreting risk estimates.

[Thermoablative therapy of hepatocellular carcinoma. Indications, technique and results]. / Thermoablative Therapie des hepatozellulären Karzinoms. Indikation, Technik und Ergebnisse.

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies worldwide. Besides liver transplantation, which is only feasible in few patients and surgical resection, the scope of potential treatment options has considerably expanded in recent years. Thermoablative therapies are now well established in early HCC due to the low rate of complications and short hospital stay. The disadvantage of higher relapse rates compared to surgical resection will be further diminished through technical advances regarding radiofrequency ablation and microwave ablation, as well as growing experience of users and thorough multidisciplinary selection of potential candidates for thermoablative therapy.

[Endovascular treatment of thoracic aneurisms: indications, techniques and results]. / Endovaskuläre Therapie des thorakalen Aortenaneurysmas: Indikationen, Technik und Ergebnisse.

UNLABELLED: CLINICAL ISSUE OF THORACIC ANEURYSMS: Aneurysms are among the most common diseases affecting the thoracic aorta, with a continuous increase in incidence over the recent decades. The main cause of thoracic aneurysms is atherosclerosis, which, due to the frequent lack of major symptoms and the potentially lethal complications such as ruptured aortic aneurysm, remains a challenge in clinical practice. STANDARD RADIOLOGICAL METHODS: CT angiography remains the imaging method of choice for acute aortic aneurysms, with MR angiography being increasingly used for follow-up imaging. THRESHOLD FOR TREATMENT: In the ascending aorta a diameter larger than 5-5.5 cm (descending aorta 6.5 cm) is regarded as the threshold for treatment. THORACIC ENDOVASCULAR AORTIC REPAIR: The continuous evolution of aortic stent grafting (i.e., thoracic endovascular aortic repair [TEVAR]) since Parodi, Palmaz and Dake has led to a steep rise in stent grafting procedures in recent years. PRACTICAL RECOMMENDATIONS: Particularly in elderly patients with multiple comorbidities, TEVAR is a valuable, less invasive option compared to open surgical repair.

[Computed tomography evaluation of human mandibles with regard to layer thickness and bone density of the cortical bone]. / Computertomografische Auswertung von humanen Unterkiefern hinsichtlich der Schichtstärke und Knochendichte der Kortikalis.

PURPOSE: Application of function-restoring individual implants for the bridging of defects in mandibles with continuity separation requires a stable fixation with special use of the cortical bone stumps. MATERIALS AND METHODS: Five section planes each of 100 computed tomographies of poly-traumatized patients' jaws were used for measuring the thickness of the cortical layer and the bone density of the mandible. The CT scans of 28 female and 72 male candidates aged between 12 and 86 years with different dentition of the mandible were available. RESULTS: The computed tomographic evaluations of human mandibles regarding the layer thickness of the cortical bone showed that the edge of the mandible in the area of the horizontal branch possesses the biggest layer thickness of the whole of the lower jaws. The highest medians of the cortical bone layer thickness were found in the area of the molars and premolars at the lower edge of the lower jaws in 6-o'clock position, in the area of the molars in the vestibular cranial 10-o'clock position and in the chin region lingual-caudal in the 4-o'clock position. The measurement of the bone density showed the highest values in the 8-o'clock position (vestibular-caudal) in the molar region in both males and females. CONCLUSION: The average values available of the bone density and the layer thickness of the cortical bone in the various regions of the lower jaw, taking into consideration age, gender and dentition, are an important aid in practice for determining a safe fixation point for implants in the area of the surface layer of the mandible by means of screws or similar fixation elements.

Comparison of reference points in different methods of temporomandibular joint imaging.

PURPOSE: Conventional radiography is a well-established method for imaging of the temporomandibular joint (TMJ) structures. However, the dental computer tomography becomes more important for the visualization of teeth in the jaw-bone. The applicability of dental computer tomography for the visualization of the TMJ it not yet been proven. The aim of the study was to identify TMJ structures using reference points with the magnetic resonance imaging (MRI) and the computed tomography (CT). METHODS: In order to compare the visualization and measurement of the TMJ a total of eight human cadaver heads was examined with CT and MRI and analysed using reference points. RESULTS: In both imaging techniques the selected reference points and distances are well definable and allow objective evaluation of anatomical structures. The CT images display a clearly better contrast to noise ratio than the MR images. The distance measurement of different width and length showed significant correlation of both images techniques. CONCLUSIONS: In TMJ diagnostics, maximum information could be obtained using both imaging techniques together due to synergistic effects.

[CT-findings in penetrating captive bolt injuries to the head and brain: analysis of the trauma-related CT-findings and review of the literature]. / CT-Befunde bei penetrierenden Kopfverletzungen durch Bolzenschussgeräte--Analyse der verletzungsspezifischen CT-Befunde und eine Übersicht über die relevante Literatur.

Penetrating gunshot injuries to the head and brain are rare in Germany and the rest of Western Europe. Due to the small number of cases over here no consistent diagnostic and therapeutic standards exist in this respect. Thus these kinds of injuries present a great challenge to the attending physicians. Most of these violations are a result of a suicidal attempt or an accident. Beside violations by firearms also penetrating injuries to the head and brain due to captive bolt devices, as used in slaughtery business for the "humane" killing of animals, occur from time to time. The impact on the head differs from that caused by firearms because no projectile is leaving the barrel and the used bolt, as a fix part of the device, does not remain in the affected tissue. That implies characteristic results within the radiological imaging that might be pathbreaking for the further treatment, because the origin of such a head injury is often unknown during primary care. Consequently the knowledge of these specific findings is central to the radiologist to make the appropriate diagnosis. Based on some clinical examples the trauma-related CT-findings are introduced and a short overview of the relevant literature is also given.

[Computed tomography: influence of varying tube current on patient dose and correctness of effective dose calculations]. / Computertomografie: einfluss des variablen röhrenstroms auf die patientendosis und die genauigkeit von berechnungen der effektiven dosis.

PURPOSE: Determination of the influence of tube currents varying during a CT scan on organ doses and on the effective dose as a function of patient constitution. Evaluation of the accuracy of effective dose calculations based on summarizing parameters (effective mAs, dose length product [DLP]) compared to calculations based on slice-specific tube currents. MATERIALS AND METHODS: Investigation of the CT datasets of 806 patients acquired from the skull base to the proximal thigh with respect to the body mass index (BMI). The effective dose was calculated by means of slice-specific as well as region-specific conversion factors. RESULTS: Dose optimization by means of variable tube current resulted in a reduction of the gonad dose in patients with BMI < or = 20 ... 21 kg/m (2) and of the effective dose in patients with BMI < or = 26 kg/m (2). Effective dose values calculated with the DLP for 90 % of the patients are within an interval of +/- 20 % of the values calculated using slice-specific tube currents. CONCLUSION: If tube current optimization during the CT scan was applied, for the scan region under investigation, at a BMI already below the German mean value, an increased effective dose was observed. Calculations of the effective dose on the basis of summarizing values such as DLP or effective mAs are of sufficient accuracy.

[O-Twist Marker for marking breast cancer under neoadjuvant chemotherapy--first results]. / Einsatz des O-Twist-Markers zur Lokalisation von Mammakarzinomen unter neoadjuvanter Chemotherapie--erste Ergebnisse.

PURPOSE: Evaluation of ultrasound-guided percutaneous marking of breast cancer using an "O-Twist Marker" (BARD GmbH, Karlsruhe, Germany) in patients undergoing neoadjuvant chemotherapy. In the event of complete remission, the lesion of interest can be missed after completion of therapy. In these cases marking of the tumor site is essential. MATERIALS AND METHODS: We monitored patients with breast cancer proven by biopsy who were undergoing neoadjuvant chemotherapy with ultrasound. In cases in which the follow-up ultrasound examination after the second chemotherapy cycle showed a significant tumor mass reduction (> 30 %), we pinpointed the lesion with an ultrasound-guided "O-Twist Marker". The position of the marker was documented by ultrasound and mammography. Between January and November 2006, we marked 7 patients. RESULTS: The visibility of the marker was excellent on mammography, but only moderate on ultrasound. The marker did not cause any imaging interference. The instrument was easy to operate. We did not detect any migration of the marker. In 3/7 patients it would have been possible to locate the remaining tumor tissue after the completion of neoadjuvant chemotherapy without the marking. In 4/7 cases the clip was very useful or even essential for preoperative site determination. CONCLUSION: The use of "O-Twist Marker" is a reliable and effective technique for locating breast cancer sites in remission during neoadjuvant chemotherapy. The visibility of the marker on ultrasound should be improved. In 57 % of the cases tumor marking was advantageous for surgical procedures.

MR-guided intervention in women with a family history of breast cancer.

OBJECTIVE: A study was undertaken to assess the clinical value of magnetic resonance (MR) imaging-guided interventions in women with a family history, but no personal history of breast cancer. METHODS AND PATIENTS: Retrospective review was performed on 63 consecutive women who had a family history, but no personal history of breast cancer. A total of 97 lesions were referred for an MR-guided intervention. Standardized MR examinations (1.0 T, T1-weighted 3D FLASH, 0.15 mmolGd-DTPA/kg body weight, prone position) were performed using a dedicated system which allows vacuum assisted breast biopsy or wire localization. RESULTS: Histologic findings in 87 procedures revealed 9 (10%) invasive carcinomas, 12 (14%) ductal carcinomas in situ, 2 atypical ductal hyperplasias (2.5%) and 2 atypical lobular hyperplasias (2.5%). Sixty-two (71%) benign histologic results are verified by an MR-guided intervention, retrospective correlation of imaging and histology and by subsequent follow-up. In ten lesions the indication dropped since the enhancing lesion was no longer visible. Absent enhancement was confirmed by short-term re-imaging of the noncompressed breast and by follow-up. CONCLUSION: Malignancy was found in 24%, high-risk lesions in 5% of successfully performed MR-guided biopsy procedures. A 57% of MR-detected malignancies were ductal carcinoma in situ. In 10% of the lesions the intervention was not performed, since no enhancing lesion could be reproduced at the date of anticipated intervention. Such problems may be avoided if the initial MRI is performed in the appropriate phase of the menstrual cycle and without hormonal replacement therapy.

Pelvic magnetic resonance imaging after bone marrow harvest--a retrospective study in 50 unrelated marrow donors.

A total of 50 unrelated marrow donors were examined by pelvic magnetic resonance imaging (MRI) to investigate the morphological sequelae of bone marrow harvesting (BMH). Signal increase in T2-weighted sequences and contrast media enhancement in T1 sequences at the operative sites were found as typical MRI morphology 4 weeks after harvest (group A, n=16), corresponding to edema, hyperemia and proliferative activity. Although tissue repair was completed in the majority of donors 1 year after BMH, about 36% of donors in group B (n=16) had abnormal findings. These included a persistence of the 'acute injury' signal pattern (2/16, 12%), and signal alterations due to fatty marrow conversion (4/16, 24%). The proportion of MRI abnormalities increased to over 70% in two-time donors (group C, n=11), which might indicate a cumulation of tissue damage after repetitive harvests. If donors had experienced prolonged discomfort after BMH (group D, n=7), MRI revealed pathological signals in 86%. In conclusion, the MRI morphology reflects the pathophysiological reactions after BMH, including inflammation and tissue repair. A further prospective evaluation in a larger number of donors is necessary to confirm these results and to identify the factors which influence the extent and duration of tissue damage.

[Computed tomographic examination of muscle volume, cross-section and density in patients with dysgnathia]. / Computertomographische Untersuchung von Muskelvolumen, -querschnitt und -dichte bei Dysgnathiepatienten.

PURPOSE: The individual jaw position is determined by the masticatory muscle among other factors. Before surgical treatment of malocclusions, thorough evaluation of the muscles is required to estimate the relapse risk. MATERIALS AND METHODS: By means of computer tomography, lateral radiographs of the skull and denture models, the relationships between morphological parameters of the masticatory muscles and the jaw bone were analyzed. Furthermore, possible causes for the extent of the malocclusion are described. RESULTS: A patient group with deep overbite was found to have significantly higher muscle densities (measured in Hounsfield units [HU]) in the medial pterygoideus muscle (59.89 +/- 3.91 HU to 48.94 +/- 4.14 HU, p < 0.01), masseter muscle, and genioglossus muscle (p < 0.05) in comparison to open bite patients. Significant differences of the muscle cross-section were measured in the masseter muscle between patients with retroclined maxillary incisors and with an open bite (5.4 +/- 0.7 cm (2) to 3.8 +/- 0.4 cm (2), p < 0.05). CONCLUSION: The results show a correlation between different jaw positions and masticatory muscles. They also suggest that the function of each muscle may be different. Additional examinations of the muscle structures are required for verification of the influence of the masticatory muscles on facial morphology.

Transdermal estradiol improves bone density when used as single agent therapy for prostate cancer.

PURPOSE: Current androgen deprivation therapies for men with prostate cancer cause accelerated osteoporosis and a significant risk of osteoporotic fracture. We have recently shown that transdermal estradiol is an effective alternative for such patients. Here we report the impact of transdermal estradiol therapy on the bone mineral density of men with prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated with transdermal estradiol patches. Bone mineral density of the lumbar spine and the proximal femur was measured with dual-energy x-ray absorptiometry, and correlated with computerized tomography and isotope bone scan findings at 6-month intervals. RESULTS: In all measured regions bone mineral density increased with time. By 1 year mean bone mineral density +/- SEM had increased by 3.60% +/- 1.6% in the lumbar spine (p = 0.055), 2.19% +/- 1.03% in the femoral neck (p = 0.055), 3.76% +/- 1.35% in the Ward's region (p = 0.008) and 1.90% +/- 0.85% in the total hip (p = 0.031), respectively. Of 12 osteoporotic sites 4 had improvement based on World Health Organization grading. All other sites improved toward a better classification. CONCLUSIONS: Transdermal estradiol protects against bone loss in men with prostate cancer and may improve bone density in those at risk for osteoporotic fracture.