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M Reiser

Publications and source records attributed to M Reiser.

At least 343 records · Page 19Linked to original sources

Diffusion-weighted MR imaging of bone marrow: differentiation of benign versus pathologic compression fractures.

PURPOSE: To evaluate the usefulness of diffusion-weighted magnetic resonance (MR) imaging of bone marrow for differentiating between benign and pathologic vertebral compression fractures. MATERIALS AND METHODS: Thirty patients with 39 vertebral compression fractures were examined with MR imaging. Diffusion-weighted MR imaging was performed with a steady-state free precession sequence in 22 acute benign osteoporotic and/or traumatic fractures and 17 pathologic compression fractures. Biplanar radiographs, T1-weighted spin-echo (SE) MR images, and short inversion time inversion-recovery (STIR) MR images were available for all patients. The signal intensity characteristics were analyzed qualitatively and quantitatively (bone marrow contrast ratios and signal-to-noise ratios) for all sequences. RESULTS: At diffusion-weighted MR imaging, all benign vertebral compression fractures were hypo- to isointense to adjacent normal vertebral bodies. Pathologic compression fractures were hyperintense to normal vertebral bodies. Benign vertebral fractures had negative bone marrow contrast ratios at diffusion-weighted imaging, whereas pathologic vertebral fractures had positive values (P < .001). The difference in bone marrow contrast ratios for benign and pathologic compression fractures at T1-weighted SE and STIR imaging was not significant (P > .01). CONCLUSION: Diffusion-weighted MR imaging provided excellent distinction between pathologic and benign vertebral compression fractures.

Adult↗

Expression of hypothalamic peptides in mice lacking neuronal nitric oxide synthase: reduced beta-END immunoreactivity in the arcuate nucleus.

The gas nitric oxide (NO) is an important messenger in brain signaling. Along with many other functions, NO is thought to influence the expression and/or release of various hypothalamic hormones (corticotropin-releasing hormone (CRH), gonadotropin-releasing hormone (GnRH) and vasopressin). To learn more about the role of NO in neuroendocrine mechanisms, we studied in mutant mice lacking neuronal isoform of NO synthase (nNOS) the cellular expression of CRH, neurophysin (the carrier protein of vasopressin/oxytocin) and pro-opiomelanocortin (POMC), as well as of the POMC-derived peptides beta-endorphin (beta-END), alpha-melanocyte-stimulating hormone (alpha-MSH) and corticotropin (ACTH) by use of immunohistochemistry and in situ hybridization. Additionally, the remaining NO-generating capacities of the nNOS minus mice were investigated by NADPH-diaphorase histochemistry and citrulline immunohistochemistry as well as by immunohistochemical localization and Western blot analysis of endothelial NOS (eNOS) and nNOS isoforms. Amongst all hypothalamic peptides under investigation, only beta-END was found to be altered in mutant mice. A morphometric analysis of beta-END producing neurons of the arcuate nucleus revealed that significantly less cells were immunoreactive in mutant mice, whereas the expression of the precursor POMC as well as of other POMC-derived peptides was found to be unchanged. In addition to that, fewer beta-END-immunoreactive fibers were found in the paraventricular nucleus of nNOS minus mice in comparison to wild-type animals. Hence, the reduction of hypothalamic beta-END is probably a posttranslational event that might reflect a disturbed endorphinergic innervation of those hypothalamic neurons which normally express nNOS.

Animals↗

[Relevance of susceptibility-induced geometrical distortion for validity of MRI-based cartilage volume and density measurements of the knee joint].

The aim of the present study was to analyze the relevance of susceptibility-induced geometrical distortion to the accuracy of MR-based cartilage volume and thickness measurement in the human knee joint. Nine cadaveric knee joints were imaged in the sagittal plane with MRI at a resolution of 2 x 0.31 x 0.31 mm3, using a fat-suppressed gradient echo sequence, with a normal gradient orientation and also with the frequency- and phase-encoding directions changed. CT arthrographic data sets were then obtained. On the basis of 3-D constructions, we determined the cartilage volume and, with a 3-D minimal distance algorithm, the thickness distribution, of the patella, femur and tibia. Irrespective of the gradient orientation, good agreement was observed between MRI and CT arthrography in terms of cartilage volumes and maximum cartilage thickness. With a normal gradient orientation the volume was overestimated by 2.5% in MRI, and 2.3% when the gradients were changed. The maximum cartilage thickness was underestimated by 0.24 intervals (interval = 0.5 mm) with a normal gradient orientation, and by 0.22 intervals when the gradient orientation was changed. In none of the joint surfaces was a relevant difference between the two methods observed. It can be shown that, using high-resolution, fat-suppressed gradient-echo sequences--susceptibility-induced geometrical distortion has no significant effect on the accuracy of MR-based cartilage volume and thickness measurements. MRI would therefore appear suitable for the design of patient-specific finite element models with the aim of analysing load transmission in diarthrodial joints and planning surgical interventions.

Adult↗

In vivo reproducibility of three-dimensional cartilage volume and thickness measurements with MR imaging.

OBJECTIVE: Previous studies suggest that MR imaging is capable of providing accurate data on knee joint cartilage volume and thickness in vitro, but the reproducibility of these data in living subjects has not been analyzed rigorously. Our aim was therefore to determine the in vivo reproducibility of volume and thickness measurements from replicated data sets, applying three-dimensional (3D) postprocessing methods. SUBJECTS AND METHODS: Eight healthy volunteers were imaged six times at a resolution of 2 x 0.31 x 0.31 mm with a fat-suppressed fast low-angle shot 3D sequence, the knee being repositioned in between replicated examinations. Three-dimensional reconstructions of the articular cartilage surfaces were obtained from sagittal data sets, and the cartilage volumes were calculated. The thickness distribution was analyzed throughout the joint surfaces independent of the section orientation, using a previously validated 3D minimal-distance algorithm. RESULTS: In the volunteers, the coefficient of variation for replicated volume measurements ranged from 1.3% (patella) to 3.4% (lateral tibia), and the standard deviation of the individual cartilage volumes ranged from +/- 16% (lateral tibia) to +/- 22% (femur). The intraclass correlation coefficient ranged from .959 (lateral tibia) to .995 (patella). The interobserver evaluation was similar to the interscan reproducibility. The mean interscan deviation of the maximal cartilage thickness interval ranged from 0.1 to 0.3 cartilage thickness intervals (of 0.5 mm); only in rare cases did we record deviations greater than one thickness interval. CONCLUSION: MR imaging can be used to determine cartilage volume and thickness in the knee joints of living subjects with high precision, provided that a fat-suppressed gradient-echo sequence with adequate resolution and 3D digital image processing are used.

Adult↗

DIZE (dexamethasone, idarubicin, and continuous infusion of ifosfamide and etoposide): an effective and well-tolerated new regimen for patients with relapsed lymphoma.

We performed a phase II study of dexamethasone, ifosfamide, idarubicin and etoposide (DIZE) in patients with relapsed or refractory Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL). The regimen consisted of dexamethasone (20 mg i.v. days 1-4), idarubicin (8 mg/m2 i.v. days 1+2), continuous infusion (c.i.) of ifosfamide (1,000 mg/m2 days 1-4), and c.i. etoposide (60 mg/m2 days 1-4). G-CSF (5 microg/kg) was used to support neutrophil recovery from day 5. In older patients (> 60 years) the dosage of idarubicin and ifosfamide was reduced to 75% in the initial cycle. Fourty six patients (pts) were treated with a total of 131 cycles. Sixteen pts were primary resistant and 30 were relapsed. Median age was 54.3 years (range 22-75). The median number of different prior chemotherapies was 1.7 (range 1 to 5). 31/46 (67.4%) pts had advanced disease (stage III or IV); 19/46 had B symptoms. Of 43 evaluable pts the response rate was 58.1% including 11 complete remissions (CR) and 14 partial remissions (PR). Mean duration of response was 8 months (1-30+). DIZE was more effective in relapsed than in refractory high-grade NHL (74 % vs 16.6%; p < 0.001). Of four heavily pretreated pts with HL, one obtained CR and two PR (response rate 75%). Myelosuppression was generally moderate with a mean duration of leukocytopenia < 1,000/microl of 2.5 days (range 0-18) and of thrombocytopenia < 25,000/microl 1.5 days (range 0-17). One patient died of uncontrollable infection in treatment related neutropenia. No other serious toxicities apart from alopecia were observed. We conclude that DIZE is safe and effective in heavily pretreated pts with relapsed lymphoma. The continuous infusion of cytostatic drugs such as that used in the new DIZE protocol might reduce hematotoxicity.

Adult↗

Lateral ankle ligaments and tibiofibular syndesmosis. 13-MHz high-frequency sonography and MRI compared in 20 patients.

To test the ability of ultra-high frequency ultrasound (13 MHz scanner) to distinguish between intact and ruptured ligaments on the lateral side of the ankle, we examined 20 patients with an acute inversion injury with MRI and ultrasound. When judged by the MRI diagnosis, an injured anterior talofibular ligament was correctly diagnosed by ultrasound in 13 of 14 and an intact anterior talofibular ligament in 5 of 6 patients. In the case of the calcaneofibular ligament, 4 ruptured and 16 intact ligaments were diagnosed equally well with both methods. The injured anterior tibiofibular ligament was correctly diagnosed by ultrasound in 6 of 9 patients, while the intact ligament was correctly recognized in 10 of 11 patients. Our findings indicate that it is possible to distinguish injured from intact ligaments sonographically.

Fibula↗

Effect of eye closures and openings on photostasis in albino rats.

PURPOSE: To determine the effects of eye closure and opening on photostasis, the regulation of light absorption by retinal rods in the albino rat. METHODS: The approach was to measure the effect of eye closure and opening on rhodopsin bleaching in situ and to use those results to simulate what happens to rhodopsin when a living rat opens or closes its eyes during daylight exposure. Completely dark-adapted, dead albino rats, each with one eye closed or open, were exposed to a standard lighting situation. The rhodopsin bleaching rate in closed versus open eyes was measured. Rhodopsin bleached at a more reduced rate in closed eyes than in open eyes. This measured reduction of rate in closed eyes was applied to a simulation of rhodopsin bleaching in open and closed eyes. The simulation used idealized conditions to verify the simulation itself, and then it was applied to previously published photostasis results. RESULTS: Rhodopsin in closed eyes bleaches at half the rate found in open eyes. The absorption spectrum of rat red blood cells was compared with the rate rhodopsin absorption spectrum, and the comparison showed that blood does not absorb the main-band wavelengths of rhodopsin. Simulating rhodopsin bleaching with eyes closed (half intensity) and open (full intensity) during daylight hours showed a slight effect on the total number of photons absorbed in an entire day. The simulation set limits to the maximal effect of eyes open all day versus eyes closed all day. At a habitat intensity of 200 lux, for example this maximal effect (eyes always open versus always closed) was calculated to be +/- 9%. At the lowest intensity, 3 lux, this maximal effect was +/- 28%, but it is only 1% at the highest intensity, 400 lux. CONCLUSIONS: Eye closures and openings have a slight effect on photostasis in albino rats. There are two reasons for this: The eyelids reduce the effective bleaching intensity by half. Moreover, during the "dim-out" of closure, rhodopsin continues to regenerate and approaches a new, higher value. This accumulation of rhodopsin enhances the rate of photon absorption because the rate is proportional to the product (rhodopsin x intensity). Thus, the increased rhodopsin concentration in the rods partially compensates for the reduced intensity of lid closure, and the photon absorption rates, with eyes closed, do not decrease by the full factor of 2 implied by the intensity reduction. In addition, when the eyes are subsequently opened after such a dim-out, the retina is suddenly exposed again to the full intensity of the environment. At this time, photon absorption rate, rhodopsin x intensity, is transiently higher than just before eye opening. Thus, the compensatory interplay between bleaching and regeneration in closed and open eyes results in the near compensation of light absorption and maintenance of the stasis close to 10(16) photons per eye per day.

Absorption↗

Experiences with novel techniques for reduction of stent flow in transjugular intrahepatic portosystemic shunts.

The transjugular intrahepatic portosystemic shunt (TIPS) may deteriorate liver function and can cause encephalopathy in patients with cirrhosis of the liver. Then reduction of TIPS flow may be required. We here report several attempts to reduce shunt flow in TIPS-induced encephalopathy or liver function impairment with novel techniques. Three patients with cirrhosis of the liver were investigated: Two with severe recurrent encephalopathy and one with impaired liver function following TIPS insertion. Insertion of a reducing stent was ineffective to decrease shunt flow velocity in one patient with severe coagulopathy. Sufficient reduction of shunt flow was achieved by embolizing the space around the hourglass waist of the reducing stent with an occlusion emulsion. Insertion of a conventional stent within the preexisting TIPS with or without additional embolization reduced TIPS flow in the other patients. After reduction of shunt flow encephalopathy improved and liver function returned to the level before TIPS, respectively. During follow-up no occlusion of TIPS was observed. Thus, reduction of shunt flow velocity can be achieved by insertion of an additional stent into a curve-shaped TIPS. Embolization can be helpful to decrease TIPS flow, particularly in patients with severe coagulopathy. Reduction of TIPS flow can correct TIPS-induced complications.

Blood Flow Velocity↗

Accuracy of cartilage volume and thickness measurements with magnetic resonance imaging.

A noninvasive imaging technique for quantifying articular cartilage is needed for diagnosis, monitoring, and therapy control in osteoarthritis. In this study the accuracy of three-dimensional cartilage volume and thickness measurements in the knee with magnetic resonance imaging was analyzed. Eight cadaveric specimens had sagittal imaging with a fat suppressed gradient echo sequence. After a contrast agent was injected, two sagittal computed tomography data sets were obtained, with the knees being repositioned between the examinations. The cartilage thickness was determined, after three-dimensional reconstruction, using a minimal distance algorithm. The mean absolute volume deviation between magnetic resonance imaging and computed tomography arthrography was 3.3% and that between the two computed tomography data sets was 3.6%. The absolute error in determining the maximal cartilage thickness with magnetic resonance imaging was on average 0.6 intervals (of 0.5-mm thickness) and that between the computed tomography examinations was 0.5 intervals. In a patient with anterior knee pain, a focal cartilage defect was seen with magnetic resonance imaging, and this was verified by arthroscopic examination. Using three-dimensional image processing, magnetic resonance imaging can provide accurate data on cartilage volume and thickness in the human knee joint surfaces. This imaging technique potentially may be valuable in the treatment of patients with joint disease.

Adult↗

Fluoroscopic MR of the pharynx in patients with obstructive sleep apnea.

PURPOSE: The purpose of our study was to introduce an ultrafast MR imaging technique of the pharynx as a diagnostic tool for viewing the mechanism of obstruction in patients with obstructive sleep apnea. METHODS: Six healthy volunteers and 16 patients with obstructive sleep apnea were examined on a 1.5-T whole-body imager using a circular polarized head coil. Ultrafast two-dimensional fast low-angle shot sequences were obtained in midsagittal and axial projections during transnasal shallow respiration at rest, during simulation of snoring, and during performance of the Müller maneuver. All patients underwent physical examination, transnasal fiberoptic endoscopy, and polysomnography. RESULTS: Five to six images were obtained per second with an in-plane resolution of 2.67 x 1.8 mm and 2.68 x 2.34 mm, allowing visualization of motion of the tongue, soft palate, uvula, and posterior pharyngeal surface. MR findings correlated well with results of clinical examination. The length of obstruction in the oropharynx, which cannot be ascertained by transnasal endoscopy of the pharynx, was clearly visible MR images. Differences between patients with obstructive sleep apnea and healthy subjects in terms of the degree of obstruction in the velopharynx and oropharynx depicted on MR images during the Müller maneuver were highly significant. CONCLUSION: We believe that ultrafast MR imaging is a reliable noninvasive method for use in the evaluation of obstructive sleep apnea.

Airway Obstruction↗

[Noninvasive analysis of cartilage volume and cartilage thickness in the human elbow joint using MRI].

The aim of the study was to non-invasively analyse the cartilage volume and thickness in the human elbow joint with magnetic resonance imaging. 12 fresh frozen specimens (ages 20 to 69 yrs.) were investigated using a 1.5 T magnet, and a water-excitation FLASH-3D sequence at a resolution of 1 x 0.25 x 0.25 mm3. After linear interpolation to 0.125 x 0.125 mm2 in the image plane, the cartilages were segmented interactively with a Snake algorithm. Following three-dimensional reconstruction, the cartilage volumes were determined, and the mean and maximal cartilage thickness computed by Euclidean distance transformation. The total cartilage volume of the human elbow joint amounted to between 3.90 and 7.17 ml (mean 5.5 ml +/- 20%). The humerus occupied 49 to 60%, the radius 15 to 27% and the ulna 20 to 29% of the total volume. The mean cartilage thickness ranged from an average of 0.9 (proximal part of the ulna) to 1.4 mm (capitulum humeri), and the maximal thickness from 2.3 mm (proximal part of the ulna) to 2.9 mm (distal part of the ulna). The ulnar cartilage showed a more inhomogeneous distribution than that of the humerus and radius. The interindividual variability of the cartilage thickness was less than that of the volume. There was no significant relationship of the volume with age (r = 0.11) or body weight (r = 0.51). However, based on the joint size (r = 0.71-medio-lateral extension of the articular surfaces) about 50% of the variability of the total cartilage volume could be predicted. The technique presented is suitable for designing computer models to investigate the load transmission and functional adaptation of diarthrodial joints, and for diagnosing and monitoring joint disease.

Adult↗

Tissue distribution and subcellular localization of a G-protein activated phosphoinositide 3-kinase. An immunohistochemical study.

We studied by light-and electron microscopic immunohistochemical techniques the anatomical distribution and subcellular localization of a G-protein activated phosphoinositide 3-kinase gamma (PI3Kgamma) in several tissues of rat, mouse, dog and man. Using monospecific polyclonal antisera and monoclonal antibodies to the enzyme protein PI3Kgamma immunoreactivity was detected in rat and mouse neutrophils, prostate, kidney, exocrine pancreas, salivary glands (parotid gland) as well as in dog and human exocrine pancreas and parotid gland. No immunoreactive material was found in Langerhans islet cells and in the nervous tissue. Fine structural analysis of PI3Kgamma immunoreactivity revealed immunolabeling of the basolateral membrane of rat kidney tubular cells and certain cells in the parenchyma of the glandular part of rat prostate gland. Our morphological data suggest a possible involvement of the enzyme in cellular transport phenomena and a regulatory influence in secretory processes.

Animals↗

[Dynamic MR-mammography in invasive lobular breast cancer].

PURPOSE: The objective of our study was to test the reliability of dynamic, contrast-enhanced MR-mammography (MR-M) in the detection of invasive lobular carcinoma (ILC) and to test if additional examination with MR-M increases the sensitivity of conventional mammography (Mx) in the detection of ILC. MATERIAL AND METHODS: We carried out 1,505 MR-Mammographies in 1,357 patients. Biopsy was indicated in 413 cases. Among the malignancies, 23/214 (10.7%) were ILC. MR-M was performed with a 1.0 T whole body MRI system with a dynamic FLASH-3D sequence. Relative signal enhancement within lesions detected and morphologic pattern of contrast enhancement (mep) were determined. Three types of mep were distinguished: type 1 without contrast enhancement, type 2 with focal contrast enhancement and type 3 with diffuse contrast enhancement of the glandular body. RESULTS: Within MR-M alone, 19/23 (82.6%) of ILC were detected due to a mep type 2. Four ILC were false negative on MR-M (2 cases show mep type 1 or mep type 3). The sensitivity of Mx alone was 86.9% (20/23). When both Mx and MR-M were combined, all 23 ILC were detected. The addition of MR-M to Mx may increase sensitivity to about 100% in the detection of ILC. CONCLUSION: Unsuspicuous MR-M (mep type 1) or diffuse uptake of contrast media (mep type 3) does not rule out malignancy in the presence of suspicious findings at Mx.

Aged↗

[Sex-specific analysis of cartilage volume in the knee joint--a quantitative MRI-based study].

The objective of the present study was to determine differences in the normal knee joint cartilage volume of males and females, the analysis of the percentage distribution of the cartilage tissue onto the various joint surfaces, and the determination of the relationship between the cartilage volume, the body weight, and the tibial head diameter. We examined the knee joints of nine healthy men and nine women with a low level of physical activity. The cartilage volume was assessed with magnetic resonance imaging, applying a fat-suppressed gradient-echo sequence with a resolution of 2 x 0.31 x 0.31 mm3 and 3D image reconstruction. In the men, the absolute volumes of the femur and tibia, but not those of the patella, were significantly higher than in the women. The differences between the sexes were considerably lower after normalisation to the body weight and the tibial head diameter and were no more statistically significant. The interindividual variability was reduced after normalisation to these two parameters, the body weight being more effective. We did not observe sex-specific differences in the percentage of the total cartilage volume taken up by the various joint surfaces. Our results suggest that, in young individuals without cartilage lesions, there exist sex-specific differences of the cartilage volume in the knee joint. However, these can be explained in terms of general differences in body constitution (body weight and bone size), without further significant influences of the sex. The knowledge of the normal, sex-specific cartilage volume is relevant when attempting to estimate the amount of tissue loss at the time at which symptoms occur in a patient with degenerative joint disease.

Adult↗

[Preoperative marking of non-palpable mammary lesions on the magnetic resonance image using a body coil].

PURPOSE: To evaluate the efficacy of a MRI localization procedure using a non-dedicated body coil in lesions only visible in MRI. MATERIAL AND METHODS: In 18 patients, we performed a contrast enhanced (i.v. 0.2 mmol Gd-DTPA/kg b.w.) breast MRI on a 1.0 Tesla system (Magnetom Impact, Siemens, Erlangen, Germany) using a body coil and a GRE 3D sequence. In prone position, the patients were placed in a customized positioning device offering lateral access to the breast. The localizations were done with a MRI-compatible wire (n = 21). In addition, all patients underwent the same imaging protocol using a dedicated breast coil (without localization). For both MRI modalities, the signal intensities of the lesion, the normal breast tissue, and the background noise were measured. The lesion-to-fat contrast (LFC), the lesion-to-fat contrast (LFC), the lesion-to-breast tissue contrast (LBC) and the percentage of signal change pre and post contrast administration were calculated and compared. The localisation results were correlated to pathologic findings. RESULTS: There was no difference in lesion detection (lesion size: 0.5 to 1.2 cm) between the body coil and the dedicated breast coil. Regarding the LFC and LBC, the body coil was superior to the dedicated breast coil (no statistical significance). However, the background noise was higher using the body coil. In all cases the localisation was successful. CONCLUSION: In our preliminary experience, detection of breast lesions and wire-localization of the lesion by MRI is efficient and reliable using a non-dedicated body coil.

Adult↗

[Control of the patency of coronary artery bypasses with contrast enhanced magnetic resonance angiography].

Contrast-enhanced 3D magnetic resonance angiography (MRA) has the potential for being a reliable method for CABG visualization and CABG patency determination in early postoperative period. 3D reconstruction was helpful in delineating CABG course and in several cases in detecting stenosis of coronary arteries. Compared to coronary angiography MRA is a non-invasive examination technique without iodine contrast medium and X-ray and is practicable in 30 min with minimal risk and low costs.

Aged↗

Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients.

OBJECTIVE: To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors. DESIGN AND SETTING: Retrospective study in two German tertiary care treatment centres. PATIENTS: A total of 198 HIV-infected patients treated with protease inhibitors in 1996. MAIN OUTCOME MEASURES: Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures. RESULTS: A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001). CONCLUSION: An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.

Adult↗