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Ezziddin S.,University of Bonn | Sabet A.,University of Bonn | Heinemann F.,University of Bonn | Yong-Hing C.J.,University of British Columbia | And 6 more authors.
Journal of Nuclear Medicine | Year: 2011

Peptide receptor radionuclide therapy (PRRT) is an efficient treatment for gastroenteropancreatic neuroendocrine tumors (GEP NETs), with outstanding overall response rates and survival. However, little is known about the particular efficacy regarding bone metastasis (BM). Methods: We retrospectively analyzed a consecutive subgroup of 42 patients with BM of GEP NETs treated with PRRT (177Lu-octreotate, 4 intended cycles at 3 monthly intervals [10-14 wk]; mean activity per cycle, 8.1 GBq). Availability of restaging and outcome data was required for patient inclusion. Baseline characteristics, including age, tumor origin, performance score, Ki-67 index, tumor load, tumor uptake, plasma chromogranin A, and neuron-specific enolase, were analyzed regarding impact on tumor regression (modified M.D. Anderson criteria) and time to progression. Survival analyses were performed using Kaplan-Meier curves, log-rank test at a significance level of P less than 0.05, and Cox proportional hazards model for uni- and multivariate analyses. Results: Median follow-up was 32 mo. The observed response of BMs consisted of complete remission in 2 (4.8%), partial remission in 14 (33.3%), minor response in 5 (11.9%), stable disease in 16 (38.1%), and progressive disease in 5 (11.9%) patients. Median progression-free survival and overall survival (OS) were 35 mo (26-44, 95% confidence interval) and 51 mo (37-65, 95% confidence interval), respectively. Patients with responding BMs (complete remission, partial remission, or minor response) exhibited a trend toward better OS (median OS not reached after 53 mo) when compared to nonresponding patients (39 mo, P 5 0.076). Only Ki-67 index (>10%) and chromogranin A level (>600 ng/mL) contributed to regression analysis. Conclusion: BM of GEP NETs is effectively controlled by PRRT, with long progression-free survival and OS. Poor patient condition and multifocality of BMs do not clearly affect treatment efficacy, possibly encouraging the use of PRRT in advanced bone metastatic disease. Larger studies are needed to assess predictors of treatment outcome in these patients. Copyright © 2011 by the Society of Nuclear Medicine, Inc. Source


Ezziddin S.,University of Bonn | Adler L.,University of Bonn | Sabet A.,University of Bonn | Poppel T.D.,University of Duisburg - Essen | And 7 more authors.
Journal of Nuclear Medicine | Year: 2014

The tumor proliferation marker, Ki-67 index, is a well-established prognostic marker in gastroenteropancreatic neuroendocrine neoplasms (NENs). Noninvasive molecular imaging allows whole-body metabolic characterization of metastatic disease. We investigated the prognostic impact of 18F-FDG PET in inoperable multifocal disease. Methods: Retrospective, dual-center analysis was performed on 89 patients with histologically confirmed, inoperable metastatic gastroenteropancreatic NENs undergoing 18F-FDG PET/CT within the staging routine. Metabolic (PET-based) grading was in accordance with the most prominent 18F-FDG uptake (reference tumor lesion): mG1, tumor-to-liver ratio of maximum standardized uptake value ≤ 1.0; mG2, 1.0-2.3; mG3, >2.3. Other potential variables influencing overall survival, including age, tumor origin, performance status, tumor burden, plasma chromogranin A (≥600 μg/L), neuron-specific enolase (≤25 μg/L), and classic grading (Ki-67-based) underwent univariate (log-rank test) and multivariate analysis (Cox proportional hazards model), with a P value of less than 0.05 considered significant. Results: The median follow-up period was 38 mo (95% confidence interval [CI], 27-49 mo); median overall survival of the 89 patients left for multivariate analysis was 29 mo (95% CI, 21-37 mo). According to metabolic grading, 9 patients (10.2%) had mG1 tumors, 22 (25.0%) mG2, and 57 (64.8%) mG3. On mul-tivariate analysis, markedly elevated plasma neuron-specific eno-lase (P = 0.016; hazard ratio, 2.9; 95% CI, 1.2-7.0) and high metabolic grade (P = 0.015; hazard ratio, 4.7; 95% CI, 1.2-7.0) were independent predictors of survival. Conclusion: This study demonstrated the feasibility of prognostic 3-grade stratification of meta-static gastroenteropancreatic NENs by whole-body molecular imaging using 18F-FDG PET. COPYRIGHT © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc. Source


Dieckhoff P.,University of Marburg | Runkel H.,University of Marburg | Daniel H.,Institute of Medical Biometry | Wiese D.,University of Marburg | And 8 more authors.
Digestion | Year: 2014

Background: Resection with curative intention is the cornerstone of treatment in patients with neuroendocrine tumors. A proportion of patients will relapse after R0 resection, but the factors predictive of recurrence are not well understood. Methods: A database established 1998 at the University Hospital Marburg was queried for all patients with documented R0 resection. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Uni- And multivariate analyses were performed. Results: 180 patients with a median age of 52 years entered the analysis. We observed 77 recurrences after a median time of 2.9 years. 24% of the recurrences occurred later than 5 years after operation. Median recurrence-free survival of the whole cohort was 101 months. In univariate analysis grade by Ki-67, stage, high lymph node ratio and microangioinvasion were significant predictors of recurrence. On multivariate analysis these parameters were confirmed as independent prognostic parameters with stage and microangioinvasion being the most important predictors. Conclusions: After R0 resection of neuroendocrine tumors, postoperative surveillance should be extended to at least 10 years. Patients with distant metastases and microangioinvasion are at high risk of recurrence. Clinical trials of adjuvant treatment protocols are indicated in these patients. © 2014 S. Karger AG, Basel. Source


Trapp C.,University of Bonn | Schiller W.,University of Bonn | Mellert F.,University of Bonn | Halbe M.,University of Zurich | And 3 more authors.
Thoracic and Cardiovascular Surgeon | Year: 2015

Background During the last decades many efforts have been made to reduce transfusion requirements and adverse clinical effects during cardiopulmonary bypass (CPB). The minimal extracorporeal circulation (MECC) system and the technique of retrograde autologous priming (RAP) of a conventional CPB circuit have been associated with decreased hemodilution. Our study aimed to compare conventional CPB (cCPB), RAP, and the ROCsafe MECC (Terumo Europe N.V., Leuven, Belgium) system in elective coronary artery bypass patients. Patients and MethodsData were retrospectively collected on three cohorts of 30 adult CPB patients. Patients were operated using cCPB, RAP, and the ROCsafe MECC system. ResultsThe three groups were comparable in demographic data. The priming volume in the ROCsafe and RAP group was significantly less compared with the conventional priming group (p <0.05). The mean time of extracorporeal circulation and aortic cross-clamp time (p <0.05) were significantly shorter in the ROCsafe group. The levels of hemoglobin (Hb) and hematocrit (Hct) during CPB and postoperatively showed significant differences between the three groups (p〈0.05) and resulted in significantly higher blood transfusion requirements (p〈0.05). Lactate, serum creatinine, troponin, and creatine kinase-myocardial band (CK-MB) levels did not differ significantly among the three groups (p >0.05). There was also no statistically significant difference in ventilation time, intensive care unit (ICU) stay, overall hospital stay, and postoperative complications (p >0.05). ConclusionIn conclusion, RAP is compared with cCPB and MECC a safe and low-cost technique in reducing the priming volume of the CPB system, causes less hemodilution, and reduces the need for intra- and postoperative blood transfusion. © 2015 Georg Thieme Verlag KG Stuttgart. Source


Meyer S.,Saarland University | Sander J.,Saarland University | Graber S.,Institute of Medical Biometry | Gottschling S.,Saarland University | Gortner L.,Saarland University
Journal of Paediatrics and Child Health | Year: 2010

Purpose: Blood pressure constitutes an important parameter in the assessment of the cardiovascular status in preterm infants. Invasive arterial blood pressure (IBP) is considered the 'gold-standard', but non-invasive blood pressure (NIBP) is used frequently in preterm infants. The aim of this prospective study was to compare mean IBP and mean NIBP arterial blood pressure measurements in three subsets of preterm infants (>1500 g; 1000-1500 g, and <1000 g, and >31 weeks, 28-31 weeks, and <28 weeks of gestation). Methods: Prospective, simultaneous assessment of both IBP and NIBP measurements in 50 preterm neonates at 6, 12, 18, 24 h after birth in a tertiary University centre. Results: Mean gestational age was 26.7 ± 2.2 (24-32) in group I (n = 18), 29.6 ± 2.0 (27-34) in group II (n = 19) and 32.2 ± 1.9(30-36) weeks in group III (n = 13), respectively; mean birth weight was 777 ± 161 (495-995), 1251 ± 154 (1010-1490) and 2010 ± 332 (1590-2550) g. Mean IBP and mean NIBP increased significantly during the first 24 h of life in all three sub-groups (P < 0.01); IBP and NIBP measurements were significantly correlated, and showed good agreement, irrespective of birth weight and gestational age. Conclusions: Although IBP monitoring is considered the 'gold standard', NIBP values showed good agreement with those obtained invasively irrespective of gestational age and birth weight. We conclude that NIBP monitoring constitutes an important parameter in the assessment of the cardiovascular status even in extremely low birth weight infants. © 2010 Paediatrics and Child Health Division (Royal Australasian College of Physicians). Source

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