[Cardiac amyloidosis and aortic valve stenosis]. / Kardiale Amyloidose und Aortenklappenstenose.

Aortic valve stenosis in old age has become a topic of interest for cardiology and cardiac surgery after the development of transvascular and transluminal minimally invasive techniques for aortic valve implantation. The observation of amyloid deposits in surgically excised valvular material led to the diagnostics of amyloidosis of the myocardium, which was discovered in up to 20% of the patients who underwent valve implantation. Clinical signs of cardiac amyloidosis, such as carpal tunnel syndrome and ruptured distal biceps tendon should be taken into account. In addition to the electrocardiogram (ECG), echocardiogram and magnetic resonance imaging, 99mtechnetium bone scintigraphy plays a key diagnostic role. The simultaneous occurrence of severe aortic valve stenosis and amyloidosis explains the special hemodynamic situation of a low gradient with low blood flow in high-grade valve stenosis. The interventional or surgical valve implantation improves the prognosis for these patients, similarly to aortic valve stenosis alone, followed by a specific pharmaceutical treatment depending on the type of amyloidosis.

Sentinel lymph node mapping with fluorescent and radioactive tracers in vulvar cancer patients.

PURPOSE: Application of radioactive tracers for sentinel lymph node biopsy (SLNB) in vulvar cancer has been established, however, the use of radioisotopes is expensive and requires complex logistics. This exploratory study evaluated the feasibility of near-infrared fluorescence-based SLNB in comparison to the gold standard using radioactive guidance. METHODS: At Evangelische Kliniken Essen-Mitte (Essen, Germany) between 02/2015 and 04/2019, 33 patients with squamous cell vulvar cancer and unifocal tumors (32 midline, 1 lateral) smaller than 4 cm underwent SLNB as part of their routine primary surgical therapy. Radiolabeled nanocolloid technetium 99 (99mTc) was injected preoperatively and indocyanine green (ICG) intraoperatively. Demographic and clinical data were retrieved from patients' records, and descriptive statistics were applied. The detection rate of the ICG fluorescence technique was compared with the standard radioactive approach. RESULTS: In patients with midline tumors, bilateral SLNB was attempted. SLNB was feasible in 61/64 (95.3%) groins with 99mTc and in 56/64 (87.5%) with ICG. In total, 125 SLNs were excised; all SLNs were radioactive and 117 (93.6%) also fluorescent. In 8 patients with BMI > 30 kg/m2, SLNB was successful in 14/15 groins (93.3%) with 99mTc and 13/15 groins (86.7%) with ICG. Upon final histology, infiltrated nodes were present in 9/64 (14.1%) groins and 10/125 SLNs; one positive SLN was not detected with ICG. CONCLUSIONS: SLNB using ICG is a promising technique, however, the detection rate obtained was slightly lower than with 99mTc. The detection rate increased over time indicating that experience and training may play an important role besides further methodological refinements.

Two progressed malignant phyllodes tumors of the breast harbor alterations in genes frequently involved in other advanced cancers.

BACKGROUND: The genomic landscape of phyllodes tumors (PTs) of the breast is not well defined, especially in patients with advanced disease. To shed light on this topic, paired primary and progressed tumor samples from two patients with malignant PTs were subjected to next-generation sequencing (NGS) followed by functional analysis of genetic alterations using two prediction tools. METHODS: The DNA of both the primary tumor and distant metastases of Patient 1 and the primary and recurrent tumor of Patient 2 were subjected to molecular profiling. NGS with the FoundationOne® assay was performed in a commercial molecular pathology laboratory. Two in silico prediction tools were used to estimate the pathogenicity of indicated genetic alterations. RESULTS: In total, 38 genomic alterations were detected, of which 11 were predicted to be probably benign. In Patient 1, 14 aberrations were identified in the primary tumor and 17 in pulmonary metastases, 12 of which were identical. In the primary and recurrent tumor of Patient 2, 17 and 15 sequence variants, respectively, were found, with 13 overlapping findings. Affected genes included seven (TP53, TERT, APC, ARID1A, EGFR, KMT2D, and RB1) of the top 10 most frequently altered genes in other advanced cancer entities, as well as four actionable therapeutic targets (EGFR, KIT, PDGFRA, and BRIP1). Of note, seven genes coding for receptor tyrosine kinases were affected: three in Patient 1 and four in Patient 2. Several genes (e.g. EPHA3, EPHA7, and EPHB1) were shown to be altered for the first time in PTs. CONCLUSIONS: The two progressed malignant PTs investigated here share some of the major genetic events occurring in other advanced cancers.

No evidence of myocardial restoration following transplantation of mononuclear bone marrow cells in coronary bypass grafting surgery patients based upon cardiac SPECT and 18F-PET.

BACKGROUND: We tested the hypothesis, that intramyocardial injection of mononuclear bone marrow cells combined with coronary artery bypass grafting (CABG) surgery improves tissue viability or function in infarct regions with non-viable myocardium as assessed by nuclear imaging techniques. METHODS: Thus far, 7 patients (60 +/- 10 [SD] years) undergoing elective CABG surgery after a myocardial infarction were included in this study. Prior to sternotomy, bone marrow was harvested by sternal puncture. Mononuclear bone marrow cells were isolated by gradient centrifugation and resuspended in 2 ml volume of Hank's buffered salt solution. At the end of CABG surgery 10 injections of 0.2 ml each were applied to the core area and borderzones of the infarct. Global and regional perfusion and viability were evaluated by ECG-gated 99mTc-tetrofosmin myocardial single-photon emission computed tomograph (SPECT) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in all study patients < 6 days before and 3 months after the intervention. RESULTS: Non-viable segments indicating transmural defects were identified in 5 patients. Two patients were found to have non-transmural defects before surgery. Concomitant surgical revascularisation and bone marrow cell injection was performed in all patients without major complications. The median total injected mononuclear cell number was 7.0 x 10(7) (range: 0.8-20.4). At 3 months 99mTc-tetrofosmin SPECT and 18F-FDG-PET scanning showed in 5 patients (transmural defect n = 4; non-transmural defect n = 1) no change in myocardial viability and in two patients (transmural defect n = 1, non-transmural defect n = 1) enhanced myocardial viability by 75%. Overall, global and regional LV ejection fraction was not significantly increased after surgery compared with the preoperative value. CONCLUSION: In CABG surgery patients with non-viable segments the concurrent use of intramyocardial cell transfer did not show any clear improvement in tissue viability or function by means of non-invasive bioimaging techniques.

Cell death induced by 131 I in a differentiated thyroid carcinoma cell line in vitro: necrosis or apoptosis?

AIM: The apoptotic and necrotic dose-response of thyroid carcinoma cells following irradiation with I was evaluated. METHODS: In our in-vitro model, cells of well-differentiated papillary thyroid carcinoma (B-CPAP) were incubated with increasing activity concentrations of I for 2 days. Changes in cell viability and the extents of necrosis and apoptosis were evaluated both immediately and 2 days after irradiation. RESULTS: Viability of B-CPAP cells diminished with increasing I activity concentration. No apoptosis was detectable immediately after irradiation. Two days after irradiation significant apoptosis was found. The lowest I activity concentration at which apoptosis was detectable corresponds to about 1 MBq . ml. At higher activity concentrations a larger percentage of cells became apoptotic but the proportion decreased again at activity concentrations >10 MBq . ml. Likewise, necrosis was minimal at low activity concentrations and showed an exponential increase with rising I activity concentrations (>5-10 MBq . ml). Necrosis was already detectable immediately after irradiation and was the predominant form of cell death at high activity concentrations. CONCLUSION: The data suggest that the nature of the cytotoxic effect of I and whether it leads to apoptotic or necrotic cell death is dose-dependent. High I doses seem to produce mainly necrotic phenomena, whereas at low I activity concentrations apoptotic phenomena prevail. The predominance of delayed apoptosis could explain why radioiodine therapy at lower doses is often linked to delayed onset and possible continuation of thyroid volume reduction over some months and even up to a year.

Differentiation between healthy thyroid remnants and tumor tissue after radioiodine therapy in patients with differentiated thyroid carcinoma using in vitro phosphorus-31 magnetic resonance spectroscopy.

BACKGROUND: The growth and spread of many tumors are triggered by changes in cell membrane metabolism, which can lead to systemic alterations in levels of phospholipids. We sought to determine whether plasma levels of several phospholipids could differentiate between healthy remnants of thyroid tissue and residual tumor tissue or metastases in patients with thyroid carcinoma. METHODS: We measured plasma phospholipid levels by phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in blood samples from 30 patients with thyroid cancer who had been rendered hypothyroid in preparation for diagnostic or therapeutic administration of iodine-131. All patients had undergone total thyroidectomy. Iodine-131 whole-body scintigraphy and measurements of thyroglobulin values during up to 3 years of follow-up were used to distinguish patients in remission from those with only healthy thyroid remnants and those with tumor tissue or metastases. RESULTS: Mean (+/- SD) levels of sphingomyelin (0.33 +/- 0.06 mmol/L vs. 0.46 +/- 0.03 mmol/L, P <0.0001) and phosphatidylcholine (1.34 +/- 0.19 mmol/L vs. 2.15 +/- 0.33 mmol/L, P <0.0001) were significantly lower in patients with metastatic thyroid cancer (n = 8) than in patients (n = 12) who were in remission. Patients with only remnants of thyroid tissue (n = 10) also had significantly lower phospholipid levels than did patients in remission, but significantly greater levels that did patients with tumor tissue or metastases. CONCLUSION: These preliminary results suggest that 31P-MRS may be useful in helping to differentiate the presence of tumor tissue, remnants of thyroid tissue not requiring further treatment, and remission in patients with thyroid cancer.

201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin: relative retention and clearance kinetics in retrogradely perfused guinea pig hearts.

Myocellular kinetics of 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin were investigated using retrogradely-perfused guinea-pig hearts. Relative retention decreased in the order 99mTc-MIBI ==> 99mTc-tetrofosmin ==> 99mTc-furifosmin. 201Tl and 99mTc-MIBI exhibited bi- (t1,t2), 99mTc-tetrofosmin and 99mTc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase elimination-half-life increased from 201Tl (t2) ==> 99mTc-MIBI (t2) ==> 99mTc-tetrofosmin (t3) ==> 99mTc-furifosmin (t3), showing a significant increase in deteriorating myocardium for all tracers but 99mTc-furifosmin. Delayed elimination in deteriorating myocardium explains at least partly the redistribution phenomenon of 201Tl, and suggests a similar phenomenon for 99mTc-MIBI and 99mTc-tetrofosmin.

(31)P and (1)h nuclear magnetic resonance spectroscopy of blood plasma in female patients with preeclampsia.

OBJECTIVE: Using (31)P and (1)H magnetic resonance spectroscopy to measure phosphorus- and hydrogen-containing metabolites, this study aimes to investigate whether or not women with preeclampsia have detectable systemic abnormalities concerning certain components of the blood plasma. METHODS: PLASMA WAS OBTAINED FROM TWO GROUPS OF WOMEN: Group 1 with preeclampsia (n=10) and Group 2, as a control group with no complications during pregnancy (n=10). Plasma analysis were performed using in-vitro (31)P and (1)H nuclear magnetic resonance spectroscopy. RESULTS: (31)P nuclear magnetic resonance (NMR) spectra showed significantly higher levels of lysophosphatidylcholine 1 in the plasma of the patients in Group 1, along with significantly decreased levels of lysophosphatidylcholine 2 and phosphatidylinositol. However, the total amount of phospholipids did not differ significantly between the groups. In addition, the (1)H NMR spectra showed a significantly lower level of HDL in samples from Group 1, and a trend towards higher plasma levels of VLDL 2 and LDL 2 in the same group. CONCLUSION: This study supports the theory that preeclampsia is a disorder in phospholipid metabolism in which malfunctioning of cellular membranes seems to play a major pathogenic role.

Clinical value of somatostatin receptor imaging in patients with suspected head and neck paragangliomas.

Paragangliomas or glomus tumours of the head and neck region are rare somatostatin receptor-expressing neuroendocrine tumours. Precise preoperative diagnosis is of special importance in order to adequately weigh the potential benefit of the operation against the inherent risks of the procedure. In this study, the clinical value of somatostatin receptor imaging was assessed in 19 patients who underwent somatostatin receptor scintigraphy because of known or suspected paraganglioma of the head and neck region. The results were compared with the results of computed tomography and/or magnetic resonance imaging, histology and clinical follow-up. [(111)In-DTPA- D-Phe(1)]-octreotide scintigraphy was performed 4-6 and 24 h after i.v. injection of 140-220 MBq (111)In-octreotide. Whole-body and planar images as well as single-photon emission tomography images were acquired and lesions were graded according to qualitative tracer uptake. Somatostatin receptor imaging was positive in nine patients, identifying paragangliomas for the first time in three patients and recurrent disease in six patients. In one patient, a second, previously unknown paraganglioma site was identified. Negative results were obtained in ten patients. These patients included one suffering from chronic hyperplastic otitis externa, one with granuloma tissue and an organised haematoma, one with an acoustic neuroma, one with an asymmetric internal carotid artery, two with ectasia of the bulbus venae jugularis and one with a jugular vein thrombosis. In two patients with a strong family history of paraganglioma, individual involvement could be excluded. In only one patient did somatostatin receptor imaging and magnetic resonance imaging yield false negative results in respect of recurrent paraganglioma tissue. It is concluded that somatostatin receptor scintigraphy provides important information in patients with suspected paragangliomas of the head and neck region and has a strong impact on further therapeutic management.