Performance and Impact of Prostate Specific Membrane Antigen-Based Diagnostics in the Management of Men with Biochemical Recurrence of Prostate Cancer and its Role in Salvage Lymph Node Dissection.

Up to 50% of patients initially treated for prostate cancer in a curative intent experience biochemical recurrence, possibly requiring adjuvant treatment. However, salvage treatment decisions, such as lymph node dissection or radiation therapy, are typically based on prostate specific antigen (PSA) recurrence. Importantly, common imaging modalities (e.g., computed tomography [CT], magnetic resonance imaging, and bone scan) are limited and the detection of recurrent disease is particularly challenging if PSA is low. Prostate specific membrane antigen (PSMA) positron-emission tomography/computed tomography (PET/CT) is a novel and promising imaging modality which aims to overcome the incapability of early identification of distant and regional metastases. Within this review, we summarize the current evidence related to PSMA-PET/CT in prostate cancer men diagnosed with biochemical recurrence after local treatment with curative intent. We discuss detection rates of PSMA-PET/CT stratified by PSA-levels and its impact on clinical decision making. Furthermore, we compare different image-fusion techniques such as PSMA-PET vs. F-/C-Choline-PET scans vs. PSMA-single photon emission computed tomography/CT. Finally, we touch upon the contemporary role of radio-guided-PSMA salvage lymphadenectomy.

MR-Guided Percutaneous Intradiscal Thermotherapy (MRgPIT): Evaluation of a New Technique for the Treatment of Degenerative Disc Disease in Cadaveric Lumbar Spine.

PURPOSE: Evaluation of MR feasibility and real-time control of an innovative thermoablative applicator for intradiscal thermotherapy and histological analysis of laser annuloplasty in human ex vivo intervertebral discs. MATERIALS AND METHODS: We evaluated a new MR-compatible applicator system for MR-guided percutaneous intradiscal thermotherapy (MRgPIT) in an open 1.0-T MRI-system. Needle artefacts and contrast-to-noise ratios (CNR) of six interactive sequences (PD-, T1-, T2w TSE, T1-, T2w GRE, bSSFP) with varying echo-times (TE) and needle orientations to the main magnetic field (B0) were analysed. Additionally, five laser protocols (Nd: YAG Laser, 2-6 W) were assessed in 50 ex vivo human intervertebral discs with subsequent histological evaluation. RESULTS: In vitro, we found optimal needle artefacts of 1.5-5 mm for the PDw TSE sequence in all angles of the applicator system to B0. A TE of 20 ms yielded the best CNR. Ex vivo, ablating with 5 W induced histological denaturation of collagen at the dorsal annulus, correlating with a rise in temperature to at least 60 °C. The MRgPIT procedure was feasible with an average intervention time of 17.1 ± 5.7 min. CONCLUSION: Real-time MR-guided positioning of the MRgPIT-applicator in cadaveric intervertebral disc is feasible and precise using fast TSE sequence designs. Laser-induced denaturation of collagen in the dorsal annulus fibrosus proved to be accurate.

Performance and Impact of Prostate Specific Membrane Antigen-Based Diagnostics in the Management of Men with Biochemical Recurrence of Prostate Cancer and its Role in Salvage Lymph Node Dissection

Modeling event-related heart period responses.

Cardiac rhythm is generated locally in the sinoatrial node, but modulated by central neural input. This may provide a possibility to infer central processes from observed phasic heart period responses (HPR). Currently, operational methods are used for HPR analysis. These methods embody implicit assumptions on how central states influence heart period. Here, we build an explicit psychophysiological model (PsPM) for event-related HPR. This phenomenological PsPM is based on three experiments involving white noise sounds, an auditory oddball task, and emotional picture viewing. The model is optimized with respect to predictive validity-the ability to separate experimental conditions from each other. To validate the PsPM, an independent sample of participants is presented with auditory stimuli of varying intensity and emotional pictures of negative and positive valence, at short intertrial intervals. Our model discriminates these experimental conditions from each other better than operational approaches. We conclude that our PsPM is more sensitive to distinguish experimental manipulations based on heart period data than operational methods, and furnishes a principled approach to analysis of HPR.

The U.S. Thrombosis and Hemostasis Centers pilot sites program.

Venous thromboembolism (VTE) is a common disorder associated with significant morbidity and mortality. Despite important advances in understanding the etiology of VTE, delivery of care to patients with thrombosis and thrombophilia is frequently incomplete and highly variable. A comprehensive model of health care has been used successfully to treat and prevent complications for people with hemophilia and other chronic disorders. The effectiveness of an integrated healthcare model for patients with all coagulation disorders has yet to be evaluated. The Division of Hereditary Blood Disorders of the Centers for Disease Control and Prevention (CDC) is collaborating with eight Thrombosis and Hemostasis Centers (pilot sites) to provide health-related services and conduct research directed toward the reduction or prevention of complications of thrombosis and thrombophilia. The initial objectives of the collaboration are to (1) determine the efficacy of integrated multidisciplinary care and prevention services for people with hemostatic disorders, (2) assess unmet needs for service delivery and identify outreach strategies to improve access to care, (3) develop effective messages aimed at disease management and prevention, and (4) foster the development of training programs to enhance provider skills for the delivery of patient care. To address these objectives, the investigators and CDC have developed and implemented a web-based patient registry to follow prospectively service allocation and patient outcomes. Funding for the program began in October 2001. All eight funded centers are affiliated with U.S. medical schools. Principal investigators at the centers are hematologists (five adult, two pediatric) or cardiologists. Faculty in obstetrics-gynecology, surgery, and multiple other specialties are integral to the model of care at the centers. Other critical components at the centers are clinical laboratory services, training programs, research networks, and education and outreach programs. From August 2003 to March 2006, over 2,600 patients were enrolled in the registry, accounting for a total of more than 5,000 visits to the centers. Immediate goals of the data collection at the centers are to characterize patients receiving care at centers and document the state of health services provided. Long-term goals are to evaluate prospectively clinical outcomes for patients receiving multidisciplinary care and prevention services at centers. The network of data collection across centers will facilitate future collaborative clinical and epidemiologic investigations and enhance collective expertise in hemostasis and coagulation disorders.

24h variation in the expression of the mt1 melatonin receptor subtype in coronary arteries derived from patients with coronary heart disease.

Previous studies presented evidence for impaired nocturnal secretion and synthesis of melatonin in patients with coronary heart disease (CHD). This study aimed to investigate whether the melatonin receptor subtype mt1 is differentially expressed in coronary arteries derived from patients with CHD (n = 9) compared to patients with dilative cardiomyopathy (CMP; n = 10) who served as controls. Expression of the mt1 receptor was studied in sections of isolated coronary arteries by a reverse transcriptase-polymerase chain reaction (RT-PCR) and a Western immunoblot technique. In addition, the data from the Western blotting of 15 patients were interpolated against the exact time of aortic clamp to study the 24h expression of the mt1 receptor. The analyses of the results from both methods indicated the presence of the mt1 receptor in all of the individuals. No statistically significant difference was observed in the receptor expression between patients with CHD and those with CMP (in arbitrary units: 3.39 +/- 3.08 versus 3.91 +/- 2.78). Expression of the melatonin receptor in the coronary arteries of the whole patient group presented a 24h variation, with the lowest values detectable after 02:00 up to the late morning hours and a progressive increase beginning after 13:00 until 00:00 (mesor = 3.66, amplitude = 3.23, acrophase = 20.45, P = .0003). When studying the 24h variation in patients with CHD and CMP separately, a nearly similar circadian course was observed. In conclusion, we demonstrated for the first time a 24h variation of a melatonin receptor subtype in human vessels. Furthermore, in relation to our results, we suggest that the expression of the mt1 melatonin receptor in the coronary arteries is probably not impaired in patients with CHD.

Laser-Induced Thermotherapy (LITT) for Retreatment of Locally Advanced Recurrences of Breast Cancer.

The effect of laser-induced thermotherapy (LITT) as a palliative method for treatment of patients with local recurrence of breast cancer is investigated. This report describes the use of interstitial laser photocoagulation to manage such lesions. The interstitial laser applications were performed in seven women with locally recurrent breast carcinoma on the chest wall after mastectomy. All patients had been heavily pretreated with conventional modes of therapy (radiotherapy, chemotherapy, hormonal therapy, surgical resection). A Nd:YAG laser with a wavelength of 1064 nm was used to heat the lesions. Heat expansion was controlled digitally and monitored by ultrasonography and colour-coded duplex sonography (CCDS). In five women this minimally invasive method enabled the precise coagulation of the subcutaneous tumour without destruction of the skin or ulceration, although these areas had been pretreated by irradiation up to 60 Gy. In two patients with extensive multiple metastases and with skin infiltration, secondary skin ulceration and delayed healing was observed. For palliative reasons, LITT under CCDS guide can aid in local control of chest wall recurrence following mastectomy in selected patients.

Effect of niacin supplementation on fibrinogen levels in patients with peripheral vascular disease.

This study demonstrates that niacin supplementation decreases plasma fibrinogen and low-density lipoprotein cholesterol in subjects with peripheral vascular disease randomized to receive niacin, warfarin, antioxidants, or placebo. Changes in fibrinogen levels are highly correlated with changes in low-density lipoprotein cholesterol (r = 0.61; p < 0.009) in subjects taking niacin.

[In vitro evaluation of MR thermometry in the implementation of laser-induced thermotherapy]. / In-vitro-Evaluierung der MR-Thermometrie zum Einsatz der laserinduzierten Thermotherapie.

PURPOSE: To optimize the MR sequences parameter for monitoring hyperthermic effects in the tissue during laser induced thermotherapy (LITT). MATERIAL AND METHODS: Experimental studies were performed for the evaluation of MR-thermometry using a contrast-agent-water solution and a pig-liver. A T1-weighted TurboFLASH sequence and a FLASH-2D sequence were used. The TurboFLASH sequence was used with various T1 settings (between 100 and 1250 ms). MR findings were correlated with temperature measurements using a fluoride optical temperature measuring system in a distance of 1, 2, and 5 cm from the laser applicator. RESULTS: Using the contrast-agent-water solution demonstrated the temperature sensitivity of both sequences. In vitro evaluations using pig liver demonstrated a near linear increase of signal versus increasing tissue temperatures in a distance of 1 cm to the tip of the laser applicator. Optimal visualization of the temperature effects was obtained using a T1 between 100 ms and 400 ms. Using the FLASH-2D sequence a signal loss was documented at a TR of 110 ms. CONCLUSION: MR-thermometry using sequentially TurboFLASH and FLASH-2D sequences allowed a non-invasive monitoring of the laser induced temperature changes.

[MR-guided laser-induced thermotherapy in tumors of the head and neck region: initial clinical results]. / MR-gesteuerte laserinduzierte Thermotherapie bei Tumoren in der Kopf-Hals-Region: Erste klinische Ergebnisse.

PURPOSE: To analyse the value of MR-guided laser-induced thermotherapy (LITT) for palliative treatment of recurrent tumours of the head and neck region. MATERIAL AND METHODS: 8 patients with recurrent tumours of the head and neck region (squamous cell carcinomas n = 6, pleomorphic adenomas n = 2) underwent MR-controlled LITT. A 7 French laser applicator was inserted under local anaesthesia into the centre of the recurrent tumour. A Nd:YAG laser with a wavelength of 1064 nm was used. Therapy was monitored on-line using special MR thermosequences. RESULTS: Preinterventional contrast-enhanced MRI revealed a recurrent tumour of the head and neck region for all eight patients. All patients tolerated the procedures well under local anaesthesia, with no clinically relevant side effects. The MR thermosequences depicted up to 15 mm diameter areas of less signal near the laser tip. Postinterventional contrast-enhanced MRI revealed hypovascularized areas due to the resulting coagulative necrosis. Coagulative necrosis of 4 cc to 28 cc occurred in all patients, and a reduction of clinical symptoms was achieved in five. CONCLUSION: The results obtained indicate that minimal invasive LITT can be a therapeutic alternative for palliative treatment of head and neck tumours.

Malignant liver tumors treated with MR imaging-guided laser-induced thermotherapy: technique and prospective results.

PURPOSE: To evaluate magnetic resonance (MR) imaging-guided laser-induced thermotherapy (LITT) of liver metastases. MATERIALS AND METHODS: In a phase II study, 20 patients with 33 metastases from colorectal carcinoma (75%) or other primary tumors (25%) underwent LITT. MR thermometry performed with fast low-angle shot sequences was used to monitor therapy on-line, and dynamic and static contrast material-enhanced MR images enabled estimation of the degree of resultant necrosis. Follow-up studies were performed 3 months after thermotherapy. RESULTS: The thermosequences enabled accurate on-line monitoring in 85% of lesions. In 69% of lesions 20 mm in diameter or smaller, contrast-enhanced MR images depicted substantial necrosis, with a local tumor control rate of 69% after 6 months and 44% after 12 months. Among lesions larger than 20 mm, necrosis was frequently incomplete, with a local control rate of only 41% after 6 months and 27% after 12 months. CONCLUSION: MR imaging-guided LITT of liver metastases is a safe and promising therapy for liver metastases.

Nd:YAG laser procedures in tumor treatment.

Due to the wide variability of tissue interactions and the possibility of specific applications, the neodymium-yttrium-aluminum-garnet (Nd:YAG) laser is the most important surgical laser. With the adequate choice of application mode and relationship between interaction time and power density, it can be used for precise cutting in the contact mode with the bare fiber, with either a wide or small coagulation seam. With a handpiece a precise focal coagulation for preparation and hemostatic purposes is possible, as well as cutting with the focussed noncontact beam where additionally a wide coagulation seam is necessary. Endoscopically guided coagulation, vaporization, and cutting are possible with bare fibers which can be introduced through nearly all endoscopes. With increasing importance, the possibility for wide and homogeneous volume coagulation is used to destroy diseased tissues either by noncontact irradiation or interstitial placement of the fiber. Thus, the field of laser application in tumor therapy ranges from the treatment of superficial tumors to endoscopic tumor ablation, resection of neoplastic tissue in parenchymatous organs, and interstitial thermotherapy with coagulation of deep-seated primary and secondary malignancies. With its different application modes the laser can be used as a surgical instrument or as a central therapeutical method, whereby perfect control of tissue interactions is always possible by using either visual control for superficial and endoscopic procedures or magnetic resonance imaging and color-coded duplex sonography as a control for interstitial procedures. During 12 years of clinical work we have developed several application modes and have proved the Nd:YAG laser to be an effective instrument in tumor therapy.

[Laser-induced thermotherapy of liver metastases with MRI control. Prospective results of an optimized therapy procedure]. / Laserinduzierte Thermotherapie (LITT) von Lebermetastasen unter MRT-Kontrolle. Prospektive Ergebnisse eines optimierten Therapieverfahrens.

In a prospective study MR-guided laser-induced thermotherapy (LITT) of liver metastases was optimized and the clinical parameters evaluated. Seventeen patients (4 women, 13 men) with a total of 29 lesions underwent LITT in 25 sessions through 1 March 1994. Twelve of them suffered from colorectal carcinomas, 5 from other primary tumors. Under local anesthesia a maximum of 5 lesions per patient were treated. For MR-guided LITT a neodymium yttrium aluminum garnet laser (Nd-YAG 1064 nm) with energy varying from 3 to 7.5 W was used. Energy and application time were defined through a computer program; they varied, dependent on the lesion size, location and consistency. To monitor the progress of LITT two special thermosensitive MR sequences (Thermo-Turbo-FLASH and FLASH-2D sequences) were individually optimized, whereby the increase in temperature correlates with an increase in signal loss. All procedures were well tolerated without significant early or late side effects. In only one patient was minimal air documentated in the pleural cavity with spontaneous resorption. Patients were dismissed without complaints after 24-h hospitalization. The control parameters of the contrast-enhanced dynamic MRI documented at optimal response a hypointense signal around the tip of the laser applicator, in accordance with laser-induced necrosis. In lesions 20 mm or smaller, nearly 100% tumor necrosis was achieved and in lesions larger than 20 mm, only 50%. Follow-up evaluation 6 months after treatment shows a significantly better response in lesions with a diameter of 20 mm or smaller, with a local tumor control rate of 66%. In lesions larger than 20 mm only a local tumor control rate of 35% could be achieved. Laser-induced thermotherapy (LITT) represents a new, minimally invasive technique for tumor destruction and a high response rate in small liver metastases.