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Showing papers by "Bethesda Hospital published in 2013"


Journal ArticleDOI
TL;DR: These evidence-based recommendations for surgical therapy reflect various “treatment corridors” that are best discussed within multidisciplinary teams and the patient considering tumor type, stage, progression, and inherent surgical risk.
Abstract: Introduction Over the past years, the incidence of thyroid cancer has surged not only in Germany but also in other countries of the Western hemisphere. This surge was first and foremost due to an increase of prognostically favorable (“low risk”) papillary thyroid microcarcinomas, for which limited surgical procedures are often sufficient without loss of oncological benefit. These developments called for an update of the previous practice guideline to detail the surgical treatment options that are available for the various disease entities and tumor stages.

220 citations


Journal ArticleDOI
TL;DR: Diagnostic leukapheresis is a clinically safe method that enabled a reliable detection of CTCs at high frequency even in nonmetastatic cancer patients, and might facilitate the routine clinical use of C TCs as in the sense of a liquid biopsy.
Abstract: Circulating tumor cells (CTCs) are promising biomarkers for diagnosis and therapy in systemic cancer. However, their infrequent and unreliable detection, especially in nonmetastatic cancer, currently impedes the clinical use of CTCs. Because leukapheresis (LA) targets peripheral blood mononuclear cells, which have a similar density to CTCs, and usually involves processing the whole circulating blood, we tested whether LA could substantially increase CTC detection in operable cancer patients. Therefore, we screened LA products generated from up to 25 L of blood per patient in two independent studies, and found that CTCs can be detected in more than 90% of nonmetastatic breast cancer patients. Interestingly, complete white blood cell sampling enabled determining an upper level for total CTC numbers of about 100,000 cells (median, 7,500 CTCs) per patient and identified a correlation of CTC numbers with anatomic disease spread. We further show that diagnostic leukapheresis can be easily combined with the US Food and Drug Administration-approved CellSearch system for standardized enumeration of CTCs. Direct comparison with 7.5 mL of blood revealed a significantly higher CTC frequency in matched LA samples. Finally, genomic single-cell profiling disclosed highly aberrant CTCs as therapy-escaping variants in breast cancer. In conclusion, LA is a clinically safe method that enabled a reliable detection of CTCs at high frequency even in nonmetastatic cancer patients, and might facilitate the routine clinical use of CTCs as in the sense of a liquid biopsy. Combined with technologies for single-cell molecular genetics or cell biology, it may significantly improve prediction of therapy response and monitoring of early systemic cancer.

177 citations


Journal ArticleDOI
TL;DR: The indications for treatment with anti-TNF agents were comparable for patients with radiographic axial SpA and those with nonradiographic axIAL SpA.
Abstract: Objective To evaluate the baseline characteristics of patients with radiographic axial spondyloarthritis (SpA; ankylosing spondylitis [AS]) and patients with nonradiographic axial SpA, to investigate determinants of anti–tumor necrosis factor (anti-TNF) agent prescription on the background of a nonrestrictive reimbursement policy, and to assess the response to TNF inhibition. Methods We compared the characteristics of radiographic axial SpA and nonradiographic axial SpA in 1,070 patients from the Swiss Clinical Quality Management (SCQM) Cohort who fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA. By taking advantage of the situation that patients who are eligible for anti-TNF treatment are preferentially enrolled in the SCQM Cohort for patients with AS/axial SpA, we explored parameters leading to the initiation of anti-TNF treatment in single and multiple regression models and assessed treatment responses. Results We confirmed a similar burden of disease (as determined by self-reported disease activity, impaired function, and quality of life) in patients with nonradiographic axial SpA (n = 232) and those with radiographic axial SpA (n = 838). Patients with radiographic axial SpA had higher median levels of acute-phase reactants and higher median AS Disease Activity Scores (ASDAS; 3.2 versus 3.0). Anti-TNF treatment was initiated in 363 patients with radiographic axial SpA and 102 patients with nonradiographic axial SpA, preferentially in those with sacroiliitis on magnetic resonance imaging, peripheral arthritis, a higher C-reactive protein (CRP) level, a higher ASDAS, and a higher Bath Ankylosing Spondylitis Disease Activity Index level. The ASAS criteria for 40% improvement responses at 1 year were higher in patients with radiographic axial SpA compared with those with nonradiographic axial SpA (48.1% versus 29.6%; odds ratio [OR] 2.2, 95% confidence interval [95% CI] 1.12–4.46, P = 0.02). The difference was smaller in the subgroups of patients with elevated baseline CRP levels (51.6% in patients with radiographic axial SpA versus 38.5% in those with nonradiographic axial SpA; OR 1.7, 95% CI 0.68–4.48, P = 0.29). Conclusion The indications for treatment with anti-TNF agents were comparable for patients with radiographic axial SpA and those with nonradiographic axial SpA. With the exception of patients with elevated CRP levels at baseline, higher rates of response to TNF inhibition were achieved in the group of patients with radiographic axial SpA than in the group with nonradiographic axial SpA.

135 citations


Journal ArticleDOI
19 Aug 2013-Trials
TL;DR: The ADAPT trial aims to combine static prognostic and dynamic predictive markers, focusing not just on single therapeutic targets, but also on general markers of proliferation and cell death, to maximally individualize therapy and avoid unnecessary toxicity by ineffective treatment.
Abstract: Adjuvant treatment decision-making based on conventional clinical/pathological and prognostic single molecular markers or genomic signatures is a therapeutic area in which over-/under-treatment are still key clinical problems even though substantial and continuous improvement of outcome has been achieved over the past decades. Response to therapy is currently not considered in the decision-making procedure. ADAPT is one of the first new generation (neo)adjuvant trials dealing with individualization of (neo)adjuvant decision-making in early breast cancer and aims to establish early predictive surrogate markers, e.g., Ki-67, for therapy response under a short induction treatment in order to maximally individualize therapy and avoid unnecessary toxicity by ineffective treatment. The prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III ADAPT trial has an innovative “umbrella” protocol design. The “umbrella” is common for all patients, consisting of dynamic testing of early therapy response. ADAPT will recruit 4,936 patients according to their respective breast cancer subtype in four distinct sub-trials at 80 trial sites in Germany; 4,000 patients with hormone receptor positive (HR+) and HER2 negative disease will be included in the ADAPT HR+/HER2- sub-trial, where treatment decision is based on risk assessment and therapy response to induction therapy, and 380 patients will be included in ADAPT HER2+/HR+. A further 220 patients will be included in ADAPT HER2+/HR- and 336 patients will be recruited for ADAPT Triple Negative. These three sub-trials focus on identification of early surrogate markers for therapy success in the neoadjuvant setting. Patients will be allocated to the respective sub-trial according to the result of their diagnostic core biopsy, as reported by local/central pathology for HR and HER2 status. Recent trials, such as the GeparTrio, have shown that response-guided therapy using clinical response may improve outcome. For chemotherapy or HER2-targeted treatment, pathologic complete response in a neoadjuvant setting is an excellent predictor of outcome. For endocrine therapy, response to short induction treatment – as defined by decrease in tumor cell proliferation – strongly correlates with outcome. ADAPT now aims to combine static prognostic and dynamic predictive markers, focusing not just on single therapeutic targets, but also on general markers of proliferation and cell death. Biomarker analysis will help to optimize selection of subtype-specific treatment. ClinicalTrials.gov: ADAPT Umbrella: NCT01781338 ; ADAPT HR+/HER2-: NCT01779206 ; ADAPT HER2+/HR+: NCT01745965 ; ADAPT HER2+/HR-: NCT01817452 ; ADAPT TN: NCT01815242 .

86 citations


Journal ArticleDOI
TL;DR: There is no evidence of an increased risk of ovarian cancer following IVF in women who give birth; nulliparous women have a marked increase in risk.

76 citations


Journal ArticleDOI
TL;DR: An overview of the tests that can be used to detect DPD deficiency are given and the advantages and disadvantages of these tests are discussed.
Abstract: 5-Fluorouracil (5-FU) is rapidly degraded by dihyropyrimidine dehydrogenase (DPD). Therefore, DPD deficiency can lead to severe toxicity or even death following treatment with 5-FU or capecitabine. Different tests based on assessing DPD enzyme activity, genetic variants in DPYD and mRNA variants have been studied for screening for DPD deficiency, but none of these are implemented broadly into clinical practice. We give an overview of the tests that can be used to detect DPD deficiency and discuss the advantages and disadvantages of these tests.

73 citations


Journal ArticleDOI
TL;DR: Women undergoing IVF treatment are at increased risk of being diagnosed with borderline ovarian tumours, according to a whole-population cohort study of women seeking hospital infertility treatment or investigation in Western Australia in 1982-2002.

55 citations


Journal ArticleDOI
TL;DR: In this paper, compartmental Michaelis-Menten elimination-based modeling has proven to be a sensitive and accurate tool for analyzing the pharmacokinetics of 5-FU and to identify patients with a dihydropyrimidine dehydrogenase deficiency.
Abstract: 5-fluorouracil (5-FU) remains the cornerstone of all currently applied regimens for the treatment of patients with cancers of the gastrointestinal tract, breast, and head and neck. Unfortunately, a large variation in the clearance of 5-FU has been observed between patients, suggesting that some patients might receive nonoptimal 5-FU doses. However, therapeutic drug monitoring of 5-FU has been shown to result in reduced intra- and inter-individual variability in 5-FU plasma levels and pharmacokinetically guided dose adjustments of 5-FU-containing therapy results in a significantly improved efficacy and tolerability. To date, compartmental Michaelis-Menten elimination-based modeling has proven to be a sensitive and accurate tool for analyzing the pharmacokinetics of 5-FU and to identify patients with a dihydropyrimidine dehydrogenase deficiency. These Michaelis-Menten models also allow the use of a limited sampling strategy and offer the opportunity to predict a priori the 5-FU plasma concentrations in patients receiving adapted doses of 5-FU.

47 citations


Journal ArticleDOI
TL;DR: While each laboratory showed good reproducibility, there was a wide range of average values relative to the consensus value from -24.0% to +22.7%.

33 citations


Journal ArticleDOI
TL;DR: Clear demographic and clinical differences were observed between T2DM patients with and without Parkinson's disease and in PD patients, metabolic control is better, potentially due to more intensive medical care.

19 citations


Journal ArticleDOI
TL;DR: Compared to Bodymass index, age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculation of %body fat, has no further benefit to predict cardiovascular disease risk factors in adult type 2 diabetic patients.
Abstract: OBJECTIVE In clinical practice Body Mass Index is generally used to evaluate overweight status in adults. The present multicenter study examines whether Body Mass Index (BMI), age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculated %body fat is a better predictor for cardiovascular disease risk factors, specifically hypertension and dyslipidemia, in a high-risk population. METHODS Data of 42 048 adult type 2 diabetic patients (median age: 67.1 years) from 161 centers in Germany (n=158) and Austria (n=3) registered in a standardized, prospective, computer-based documentation program, were included in the study. For each patient body weight, height, blood pressure and blood lipids were documented. Spearman correlation analyses as well as multivariable logistic regression models were used to examine the relationship between anthropometric measurements and cardiovascular disease risk factors. RESULTS Correlation and regression analyses revealed minor, non significant differences between the 3 anthropometric measurements (all p>0.05). In both genders, relationships between anthropometric measurements and hypertension or reduced HDL-cholesterol were nearly identical. Only for increased triglycerides, the relations with the 3 anthropometric measurements were significantly stronger in males than in females (p<0.0001, respectively). With increasing age, associations between anthropometric measurements and hypertension, reduced HDL-cholesterol or increased triglycerides became weaker. Spearman correlation coefficients for total cholesterol and LDL-cholesterol revealed weak associations with the 3 anthropometric measurements. CONCLUSION Compared to Body Mass Index, age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculation of %body fat, has no further benefit to predict cardiovascular disease risk factors in adult type 2 diabetic patients.

Journal Article
TL;DR: Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side of Sturge-Weber syndrome, and the age of epilepsy onset is related to the extent of leptomeningeal angiomatosis.
Abstract: BACKGROUNDS AND PURPOSE To correlate the extent of the leptomeningeal angiomatosis with clinical features in Sturge-Weber syndrome (SWS) METHODS The study group consisted of 86 consecutive patients aged two months to 56 (mean 79 +/- 103) years with SWS and epilepsy Clinical and MRI data were analyzed RESULTS Based on the extent of leptomeningeal angiomatosis, patients were divided into two subgroups: 43 patients had hemispheric angiomatosis and atrophy, whereas, another 43 had focal involvement Nine of the 43 hemispherial patients (10%) showed bilateral involvement: all of these bilateral cases demonstrated dominance in a single side with hemispheric leptomeningeal angiomatosis and contralateral focal extension Hemispheric and focal subgroups were clinically different Patients with hemispheric SWS were younger at the age of epilepsy onset (p < 0001) and age at MRI examination (p < 005) Neither gender, lateralization, duration of epilepsy, appearance of secondarily generalized seizures, nor seizure frequency revealed a significant difference between subgroups CONCLUSION Bilateral involvement is frequent and occurs in cases with a hemisperic involvement on one side The age of epilepsy onset is related to the extent of leptomeningeal angiomatosis Patients with hemispheric form of SWS presented with earlier age of seizure onset Focal pial angiomatoses do not tend to progress (a longer duration is not associated with more frequent hemispheric involvement) Other variables including seizure frequency and secondary generalized tonic-clonic seizures are not associated with the extent of angiomatosis

Journal ArticleDOI
TL;DR: AMH was affected by the combined oral contraceptive pill and further studies on the effect of oral contraceptives are warranted.

Journal ArticleDOI
TL;DR: The study indicated that the use of the clinical pathway in the stroke treatment improved the outcome of the patients with stroke.
Abstract: Stroke becomes world health problem all over the world because it is the causal factor of high mortality and disability. Good and well-organized process of healthcare service will improve the outcome of the patients with stroke. Clinical pathway may be used as clear standard to help reduce unnecessary variations of medical treatment and measure. The study aimed at finding out the correlation between the use of clinical pathway and the outcome of the patients with ischemic stroke in Bethesda Hospital Yogyakarta. It was an observational and analytic study with cohort restorative study design. The author compared the outcomes of acute ischemic stroke between the group with clinical pathway and the group without the clinical pathway. Data was collected using consecutive sampling from the electronic registry and medical record data of the patients from January 1 st , 2011 to December 31 st , 2011. It was conducted to 124 patients with ischemic stroke assigned to two groups (the first groups of 62 patients with clinical pathway and the second groups of 62 patients without clinical pathway). The basic characteristics of the two groups were the same. The results of the analysis showed that there was a significant decrease in the incidence of complication and a significant increase in the use of antiplatelete drugs, antidiabetic drugs and statin as secondary preventive measure of the recurrent stroke. There was not any significant difference in the duration of the hospitalized healthcare, the financing and the mortality between the two observation groups. The study indicated that the use of the clinical pathway in the stroke treatment improved the outcome of the patients with stroke. It was necessary to conduct further study to evaluate the effectiveness of the clinical pathway in improving the outcome of the patients with bigger number of the subjects and the longer period of time.