Recurrence-free long-term survival after liver transplantation in patients with 18F-FDG non-avid hilar cholangiocarcinoma on PET.

The aim of this retrospective study was to assess the value of (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG-PET) for predicting biological tumor behavior and outcome after liver transplantation (LT) in patients with otherwise unresectable hilar cholangiocarcinoma (HC). Preoperative (18)F-FDG-PET scanning was performed in 13 patients with type IV Klatskin tumor before LT. PET+ status indicated patients with an increased pretransplant (18)F-FDG uptake, whereas PET- recipients had no increased preoperative (18)F-FDG uptake on PET. Pretransplant PET findings were correlated with histopathological tumor characteristics and patient outcome after LT. Eight patients demonstrated positive preoperative PET findings (61.5%), whereas five patients had no increased preoperative (18)F-FDG tumor uptake (38.5%) on PET. One PET+ patient died after 1 month due to liver allograft dysfunction. Seven PET+ liver recipients developed tumor recurrence, whereas five PET- patients were tumor-free alive after a median of 76 months post-LT (p = 0.001). The 2-year recurrence-free survival rate after LT was 100% in PET- patients and 28.6% in the PET+ population (log-rank = 0.008). Our results suggest that patients with (18)F-FDG non-avid HC on PET may achieve recurrence-free long-term survival after LT.

18F-FDG-uptake of hepatocellular carcinoma on PET predicts microvascular tumor invasion in liver transplant patients.

Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using (18)F-fluorodeoxyglucose ((18)F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased (18)F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET-) pre-LT. PET- recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET-population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased (18)F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria.

Treatment with granulocyte-colony stimulating factor in patients with acute myocardial infarction. Evidence for a stimulation of neovascularization and improvement of myocardial perfusion.

BACKGROUND: Stem cell therapy has been suggested to be beneficial in patients after acute myocardial infarction (AMI). Strategies of treatment are either a local application of mononuclear bone marrow cells (BMCs) into the infarct-related artery or a systemic therapy with the granulocyte-stimulating factor (G-CSF) to mobilize BMCs. Nevertheless, the mechanisms responsible for improvement of cardiac function and perfusion are speculative at present. This study has been performed to investigate the effect of G-CSF on systemic levels of vascular growth factors and chemokines responsible for neovascularization, that might help to understand the positive effects of a G-CSF therapy after AMI. METHODS AND RESULTS: Five patients in the treatment group and 5 patients in the control group were enrolled in this study. The patients in the treatment group received 10 microg/kg bodyweight/day of G-CSF subcutaneously for a mean treatment duration of 6.6 +/- 1.1 days. In both groups, levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and monocyte chemotactic protein-1 (MCP-1) were measured on day 2 to 3 and day 5 after AMI. The regional wall perfusion and the ejection fraction (EF) were evaluated before discharge and after 3 months with ECG-gated MIBI-SPECT and radionuclide ventriculography, respectively. Significant higher levels of VEGF (p < 0.01), bFGF (p < 0.05) and MCP-1 (p < 0.05) were found in the treatment group compared to the control group. Levels of VEGF and bFGF remained on a plateau during the G-CSF treatment and decreased significantly in the control group. The wall perfusion improved significantly within the treatment group and between the groups (p < 0.05), respectively. The EF improved significantly within the treatment group (p < 0.05), but the change of the EF between the groups was not significant. CONCLUSION: In patients with AMI, the treatment with G-CSF modulates the formation of vascular growth factors that might improve neovascularization and result in an improved myocardial perfusion and function.

Recovery of the cardiac adrenergic nervous system after long-term beta-blocker therapy in idiopathic dilated cardiomyopathy: assessment by increase in myocardial 123I-metaiodobenzylguanidine uptake.

UNLABELLED: In chronic heart failure, elevated plasma norepinephrine (NE) levels and a disparity between the neuronal release and the effective reuptake of NE lead to an increased concentration of NE in the presynaptic cleft, causing a downregulation of the myocardial beta-adrenoceptors. The clinical and prognostic effectiveness of beta-blocker therapy has been shown in patients with chronic heart failure in several large trials. The purpose of this study was to investigate the effect of long-term beta-blocker therapy on the cardiac adrenergic nervous system as assessed by the myocardial uptake of 123I-metaiodobenzylguanidine (MIBG), an analog of NE, in idiopathic dilated cardiomyopathy (IDC). METHODS: In 10 patients with IDC and stable chronic heart failure the myocardial MIBG uptake was measured at baseline and at 1 y (median, 11.5 mo) after treatment with beta-blockers (metoprolol, n = 5; bisoprolol, n = 1; and carvedilol, n = 4) in addition to standard medication. In parallel with the changes in MIBG uptake, the New York Heart Association functional class, the left ventricular ejection fraction (LVEF), and the left ventricular end-diastolic diameter (LVEDD) were documented before and after 1 y of therapy with beta-blockers. RESULTS: During the 1-y follow-up, a significant increase in myocardial 123I-MIBG uptake (P = 0.005) in parallel with an improved LVEF (P = 0.005) and a reduced LVEDD (P = 0.019) was found. A trend toward an improvement of the New York Heart Association functional class under the beta-blocker therapy (P = 0.139) was also found. CONCLUSION: Assessment of the myocardial 123I-MIBG uptake is a useful noninvasive tool for evaluating changes in cardiac sympathetic nerve activity under medical therapy. Long-term treatment with beta-blockers in IDC causes a recovery of the cardiac adrenergic nervous system concomitantly with a clinical and hemodynamic improvement.

Cardiac sympathetic activity as measured by myocardial 123-I-metaiodobenzylguanidine uptake and heart rate variability in idiopathic dilated cardiomyopathy.

In patients with idiopathic dilated cardiomyopathy (IDC) the increased sympathetic activity owing to chronic congestive heart failure leads to an imbalance of cardiac autonomic tone, as reflected by decreased heart rate variability (HRV). Iodine-123-metaiodobenzylguanidine (123-I-MIBG), which has the same affinity for sympathetic nerve endings as norepinephrine, can be used to assess the integrity and function of the cardiac sympathetic nervous system. The aim of the present study was to measure cardiac sympathetic activity by assessing 123-I-MIBG uptake compared with HRV in patients with IDC. In 12 patients with IDC and mild to moderate heart failure, myocardial MIBG uptake was calculated from the myocardial (M) to left ventricular cavity (C) voxel values density ratio and the 123-I activity in a blood sample as a reference (= M/C ratio) using a double radionuclide study with 123-I-MIBG and technetium-99m-MIBI. To investigate the relation between myocardial MIBG uptake and HRV in time domain, the linear regression between the M/C ratio, a new scintigraphic parameter, and the mean RR interval or the HRV triangular index, respectively, was determined. A significant correlation between the M/C ratio and mean RR interval (r = 0.52; p = 0.016) or M/C ratio and HRV triangular index (r = 0.76; p = 0.003), respectively, was found. Thus, the significant correlation between the M/C ratio and HRV indicate that they are both suitable noninvasive methods for evaluating cardiac sympathetic activity in patients with IDC and, furthermore, favor the view that there is evidence of a relation between HRV and the disorder of the cardiac presynaptic sympathetic nerve endings as demonstrated by a reduced M/C ratio.

Impact of positron emission tomography on strategy in liver resection for primary and secondary liver tumors.

PURPOSE: Outcome of patients with metastatic disease mainly depends on accurate preoperative tumor staging. 18[F]fluorodeoxyglucose positron emission tomography (18F-PET) has been proven to be a valuable diagnostic tool in a number of different tumors but its direct influence on liver surgery has not been thoroughly investigated. MATERIALS AND METHODS: Between July 1999 and March 2000, 50 consecutive patients with 174 suspected liver lesions were admitted to the University Hospital Jena. All 50 patients underwent abdominal ultrasound, CT-scan, and 18-FDG positron emission tomography scanning. In 23 patients the diagnostic work-up was completed by MRI scan. RESULTS: Altogether there were a total of 174 histologically proven intrahepatic lesions, nine of which were benign. The sensitivity, specificity, and positive predictive value of PET for all hepatic lesions was 82%, 25%, and 96% compared with 63%, 50%, and 96% for abdominal ultrasound, 71%, 50%, and 97% for CT-scan, and 83%, 57%, and 97% for MRI-scan. In 23 of 50 patients 24 extrahepatic lesions were identified. In these patients the sensitivity and specificity of PET-compared to abdominal ultrasound, CT-scan, and MRI-scan for all extrahepatic lesions-was 63% and 60%, 29% and 25%, 47% and 50% and 40% and 50%, respectively. The findings on PET scan had a direct impact on operative management in nine patients (18%). CONCLUSIONS: Our series demonstrates good sensitivity and specificity for the detection of primary and secondary liver lesions which is superior to ultrasound and CT scan but not to MRI scan. The main value of PET scan consists in the detection of extrahepatic tumor (64%). Due to better detection of extrahepatic tumor, FDG-PET is a very useful addition to the currently used anatomically-based images in all cases of advanced tumor spread with high risk of extrahepatic tumor.

Radioimmunodetection of neuroblastoma cells with I-131-radiolabelled antibodies.

The murine anti-neuroblastoma monoclonal antibodies 15/7 and 19/1/4 should be tested for specific radiolocalization of neuroblastoma by immunoscintigraphic imaging of this tumour growing in mice. Radioiodination of both antibodies was done by chloramine-T method resulted in an immunoreactivity of 75%. The calculated specific activity varied from 51.1 to 126.2 kBq/microgram IgG. In each case, about 500 kBq of labeled antibodies were intraperitoneally injected into human neuroblastoma (SK-N-MC, SK-PN-DW and IMR 5) xenografted severe complete immunodeficient (SCID) mice. Whole-body scintigraphy was performed daily by a scintiscanner to localize the tumour site. After last scanning principal organs were removed and their I-131-uptake was determined by measuring the impulse rate. The best scintigrams were done with I-131-19/1/4 at the second day after antibody injection. Radioconjugates were accumulated at highest in the tumour at the third day after application of 15/7 and 19/1/4 with a tumour uptake of 0.4 and 2.2 per cent of injected dose per gram (%ID/g), respectively. The 15/7-moAbs was accumulated approximately 9-fold higher in the SK-N-MC and SK-PN-DW grafts than in principal organs, whereas the tumour/non-tumour-ratio of the 19/1/4 moAb was 3:1. The results indicate the efficacy of these two neuroblastoma antibodies in radiolabelling and their usefulness for tumour imaging of neuroblastoma engrafted SCID-mice.

[Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study]. / Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study.

Transmission measurements are performed in SPECT to correct for attenuation of the gamma quanta in the body. In this study, we measured the additional radiation dose caused by transmission scans using a field of collimated 153Gd rod sources. Two measurement series were performed with an anthropomorphic phantom and thermoluminescence dosimeters. For a typical SPECT study, we found a mean dose rate of 2.2 +/- 0.8 micro Sievert per hour (range: 1.2-3.9 micro Sievert per hour). For a measurement time of 20 min, this corresponds to a mean equivalent patient radiation dose of 0.73 micro Sievert. Thus, the radiation exposure caused by transmission scans can be neglected compared to the radiopharmaceutical dose and may not be considered as a limiting factor for the clinical application of attenuation correction in SPECT.

[Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study]. / Assessment of radiation exposure caused by transmission scans in SPECT: an anthropomorphic dosimetry study.

Transmission measurements are performed in SPECT to correct for attenuation of the gamma quanta in the body. In this study, we measured the additional radiation dose caused by transmission scans using a field of collimated 153Gd rod sources. Two measurement series were performed with a anthropomorphic phantom and thermoluminescence dosimeters. For a typical SPECT study, we found a mean dose rate of 2.2 +/- 0.8 micro Sievert per hour (range: 1.2-3.9 micro Sievert per hour). For a measurement time of 20 min, this corresponds to a mean equivalent patient radiation dose of 0.73 micro Sievert. Thus, the radiation exposure caused by transmission scans can be neglected compared to the radiopharmaceutical dose and may not be considered as a limiting factor for the clinical application of attenuation correction in SPECT.

Increased 18F-FDG uptake of hepatocellular carcinoma on positron emission tomography independently predicts tumor recurrence in liver transplant patients.

The aim of this retrospective trial was to analyze the value of preoperative (18)F-fluoro-deoxyglucose positron emission tomography ((18)F-FDG PET) to predict parameters of tumor aggressiveness among liver transplant (OLT) patients with hepatocellular carcinoma (HCC). Fifty-five patients with HCC underwent (18)F-FDG-PET during evaluation for OLT. Nineteen patients demonstrated increased (18)F-FDG uptake on PET pre-OLT (PET(+)), and 36 patients revealed negative PET findings (PET(-)). PET(+) patients showed a relative risk of 9.5 and 6.4 for poor differentiation and for microvascular invasion (MVI) in the HCC at explant pathology, respectively. Of the 10 patients (18.2%) who developed HCC recurrences, 9 (90%) revealed increased (18)F-FDG uptake pre-OLT; only 1 (10%) showed a PET(-) status (P < .001). Apart from poor tumor differentiation, PET(+) status was identified as an independent predictor of tumor recurrence post-OLT (odds ratio, 23.9). Our study demonstrated that (18)F-FDG uptake on PET is a reliable preoperative predictor of tumor recurrence after OLT in patients with HCC, triggered by its high association with poor tumor differentiation and MVI.

[The hemodynamic profile of pentaerythrityl tetranitrate]. / Zum hämodynamischen Wirkungsprofil von Pentaerytrithyltetranitrat.

On altogether 17 patients with different stages of the chronic ischaemic heart disease before and after oral application of 20 and 40 mg PETN in form of Pentalong HR, AP, PAEDP and CO were measured. According to this PETN proves to be haemodynamically active, since in the optimum of the effect it reduces the PAEDP independent on the initial pressure by on an average 30-40%. The beginning of the effect lies between 30 and 45 min. The duration of the effect is prolonged, when 40 mg are used. A consequent nitrotherapy with PETN demands 4-6 times 40 mg, in these cases remains without any side-effects and is indicated in accumulated angina pectoris for smoothing the course of PAEDP, in angina pectoris with latent or manifest left heart insufficiency and in increase of the filling pressure after acute myocardial infarction.

[Thyroid diseases in advanced age]. / Schilddrüsenerkrankungen im höheren Lebensalter.

Nearly all diseases of the thyroid, such as nodular goitre, thyroid carcinoma, non-immunogenic hyperthyroidism and idiopathic hypothyroidism, exhibit an increase in frequency with age. Their recognition is rendered more difficult by the often oligosymptomatic, ambiguous clinical picture, but it is the timely treatment that is of particular prognostic importance to an organism weakened due to polymorbidity. In all hard nodular alterations, a malignoma must be ruled out by sonography, scintigraphy and cytopuncture. In all iodine-deficient regions such as the GDR, a frequent occurrence of thyroid autonomy with manifestation of hyperthyroidism following iodine contamination has to be taken into account. Hypothyroidism is often misinterpreted as age-related changes. By employing adequately modern in vitro methods and imaging procedures it will be possible to further improve diagnosis and prognosis of the thyreopathy in the old age ranges.

[The value of fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiation of pancreatic lesions]. / Die Wertigkeit der Fluordeoxyglukose Positronenemissionstomographie (FDG-PET) in der Diagnostik von Pankreasprozessen.

Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is a functional imaging modality that is based on the metabolic activity which is higher in most malignant tumors than benign tissues. This short review describes the basics of FDG-PET and gives a discussion of its role in differentiation of focal pancreatic lesions. The diagnostic accuracy in patients with active inflammation or cancer of the pancreas can be improved by dynamic acquisition of focal pancreatic lesions.

[The value of lung perfusion scintigraphy in radiation pneumonitis in comparison with the diffusing capacity DLCO]. / Der Aussagewert der Lungenperfusionsszintigraphie bei der Strahlenpneumonitis im Vergleich zur Diffusionskapazität DLCO.

The value of lung perfusion scintigraphy (Tc99m) and lung diffusing capacity are compared with references to early detection of radiogenic pneumonitis. Perfusion scintigraphy completed by diffusing capacity is excellent suitable for early detection. Risk cases are recognized up to 40 days earlier than by X-ray. Severity of radiogenic pneumonitis can be diminished remarkable by prevention therapy.

[The measurement of bronchial mucociliary clearance using 99mTc for evaluating the success of the salt water cure]. / Messung der bronchialen mukoziliaren Clearance mittels 99mTc zur Objektivierung des Erfolges der Solekur.

We found a highly significant improvement in the pulmonary mucociliary clearance in the peripheral region of the lungs four weeks after saline spring treatment. We examined the possibility of applying the saccharin sky-blue test for evaluating the success of spa treatment.

[Anemia in chronic hemodialysis]. / Die Anämie bei chronischer Hämodialyse.

On the basis of general haematological, clinicochemical, cytomorphological, cytochemical and nuclearmedical investigations the anaemia of chronic haemodialysis can be considered as a renal anaemia modified by a permanent dialysis. It is less characterized by lack of erythropoietin, but more by a strong lack of iron, moderate haemolysis and slight deficiency of folic acid. After gradual diagnostics the substitution treatment with iron is absolutely necessary, medication of folic acid should be attempted. A permanent therapy with 80-120 mg of iron weekly administered parenterally can be successfully performed and 10-15 mg of folic acid daily, which will markedly lower the rate of transfusion.

[Permeability of the arterial vessel wall for labeled plasma proteins]. / Die Permeabilität der arteriellen Gefässwand für markiertes Blutplasms-Protein.

The permeability of the large arteries may be analysed by different methods. It is of different size in the individual arteries and is increased by hypoxia, by hypertension and by mediators. Thus increasedly atherogenic substances may enter the wall of the vessel.

Arterial permeability to labeled protein.

Labeled albumin, which was administered intravenously, was detected, with the use of a scintillation counter, in the aortic wall of rabbits. Relative to weight, the permeability index was highest in the aortic arch and abdominal aorta and lowest in the medial thoracic aorta. Angiotensin II and various mediators were found to increase the permeability of the aortic wall.

[Differential hemodynamically oriented therapy in the early hospital phase of acute myocardial infarction]. / Hämodynamisch orientierte Differentialtherapie in der hospitalen Frühphase des akuten Myokardinfarktes.

100 patients with acute myocardial infarction were examined by means of catheterization of the pulmonary artery, dilution of isotopes and phonoelectrocardiography immediately after admission to the clinic and under a therapy following haemodynamic viewpoints within 2-24 hours after the beginning of the treatment, taking into consideration 15 parameters. According to a classification of the behaviour of the coronary circulation into normal function, hypovolaemia, hyperfunction, compensated insufficiency of the left heart, forward failure, retrofailure and cardiogenic shock the differential-therapeutic approach is described and the effects are explained. The haemodynamic examinations render possible the recognition of beginning circulatory complications still before their clinical manifestation, they result in founded therapeutic methods which are aimed at the correction of incorrect parameters which affect the O2-balance of the myocardium and thus the protection of the myocardium as well as the stability of the circulation, they allow a prognostic assessment of the course of the infarction and are suited to reduce the mortality of acute myocardial infarction in the early hospital phase by early recognition of developing pumping disturbances and their early treatment.