Symptom Burden and Factors Associated with Acute Respiratory Infections in the First Two Years of Life-Results from the LoewenKIDS Cohort.

Acute respiratory infections (ARIs) are the most common childhood illnesses worldwide whereby the reported frequency varies widely, often depending on type of assessment. Symptom diaries are a powerful tool to counteract possible under-reporting, particularly of milder infections, and thus offer the possibility to assess the full burden of ARIs. The following analyses are based on symptom diaries from participants of the German birth cohort study LoewenKIDS. Primary analyses included frequencies of ARIs and specific symptoms. Factors, which might be associated with an increased number of ARIs, were identified using the Poisson regression. A subsample of two hundred eighty-eight participants were included. On average, 13.7 ARIs (SD: 5.2 median: 14.0 IQR: 10-17) were reported in the first two years of life with an average duration of 11 days per episode (SD: 5.8, median: 9.7, IQR: 7-14). The median age for the first ARI episode was 91 days (IQR: 57-128, mean: 107, SD: 84.5). Childcare attendance and having siblings were associated with an increased frequency of ARIs, while exclusive breastfeeding for the first three months was associated with less ARIs, compared to exclusive breastfeeding for a longer period. This study provides detailed insight into the symptom burden of ARIs in German infants.

Effect of ibandronate on disseminated tumor cells in the bone marrow of patients with primary breast cancer: a pilot study.

BACKGROUND: Breast cancer patients may experience disease relapse even 10-20 years after primary diagnosis. Recurrence is caused by dormant disseminated tumor cells (DTCs) in the bone marrow (BM). Whereas chemotherapy is unable to eradicate these non-proliferating cells, bisphosponates are currently being discussed as eliminating DTCs. The purpose of our study was to: i) analyze the presence of DTCs in the BM of breast cancer patients 2-10 years after first diagnosis of cancer, and ii) to study the effect of ibandronate on DTCs in those patients with DTC persistence. PATIENTS AND METHODS: Bilateral BM aspirates of 54 individuals diagnosed 2-10 years ago with breast cancer, but currently disease free, were analyzed for DTCs by immunocytochemistry using pan-cytokeratin antibody A45-B/B3. Patients with DTC persistence received oral ibandronate treatment (50 mg per day) for six months and bilateral BM aspirates were analyzed for DTCs again after therapy. RESULTS: DTCs were found in 18/54 (33%) of the patients, with a median number of 3 disseminated tumor cells (range 1-6 cells). These 18 patients received ibandronate orally for 6 months and 17/18 patients were analyzed for DTCs again after therapy. Only 3/17 (18%) patients remained DTC-positive, with the detection of 1 (n=2 patients) and 3 DTCs, respectively. These three DTC-positive patients continued their ibandronate intake for a further six months and re-examination of the BM resulted in no detection of DTCs in any of the three patients. CONCLUSION: Our pilot study indicates the potential effect of ibandronate on DTCs and further studies are needed to demonstrate these findings in a larger patient cohort.

[Screening for distress in women with breast cancer diagnosed for the first time: employment of HADS-D and PO-Bado]. / Screening von psychischen Belastungen bei erst erkrankten Brustkrebspatientinnen: Einsatz von HADS-D und PO-Bado.

OBJECTIVES: In the context of an intensification of efforts to ensure sufficient psychooncological care for breast-cancer patients, the discussion concerning valid psychometric screening instruments gains a special relevance. METHODS: The discriminant and diagnostic validity of HADS-D and PO-Bado were investigated in a sample of 123 women with breast cancer diagnosed for the first time. RESULTS: An ROC analysis revealed a cut-off score of greater than 9 for the subscale anxiety (sensitivity: 50%; specificity: 90%) for the use of HADS-D among breast cancer patients, whereas the recommended cut-off value was greater than 7 (sensitivity: 56%; specificity: 80%) for the subscale depression. Based on the anxiety and depression scores measured by HADS-D, 74% of the clinical cases could be classified correctly. Scores for physical and mental distress measured with PO-Bado were significantly lower in the investigated sample than in the control sample. CONCLUSIONS: HADS-D has only a moderate sensitivity for the group at hand. PO-Bado is a comprehensive basic documentation for specific psychooncological distress, though without cut-off values it is not useful as a screening instrument.

Speed of haemoglobin response in patients with cancer: a review of the erythropoietic proteins.

BACKGROUND: Patients with cancer-related anaemia generally have a poor prognosis. Evidence suggests that an effective erythropoietic protein (epoetin)-mediated haemoglobin (Hb) response provides marked improvement in quality of life (QoL). An early Hb response to erythropoietic protein therapy in these patients would appear ideal but few studies have compared the speed of response to different erythropoietic proteins, or the potential benefits associated with an early Hb response. RESULTS AND DISCUSSION: The pharmacokinetic/pharmacodynamic profiles of commercially available erythropoietic proteins are reviewed along with available clinical data to examine Hb response and associated clinical outcomes for each of these agents. Randomised, head-to-head trials comparing epoetin alfa and darbepoetin alfa suggest that patients administered with epoetin alfa achieve a satisfactory Hb response significantly earlier than those given darbepoetin alfa, and with consistently lower monthly transfusion rates. Non-comparative studies support this, suggesting also that epoetin beta may provide a relatively faster Hb response in a greater number of patients than either epoetin alfa or darbepoetin alfa, irrespective of malignancy or chemotherapy type. Moreover, studies suggest consistently that a 'front-loading' dosing regimen with epoetin alfa does not convey improved speed of Hb response over epoetin beta administered according to current clinical practice guidelines. CONCLUSIONS: Given the poor prognosis of anaemic patients with cancer, the use of an agent which provides clinical benefits quickly but with minimal thromboembolic risk, should be considered an essential component of anaemia management in these patients. However, more head-to-head studies are required to confirm the relative efficacy of currently available erythropoietic proteins.

Whole-body MR imaging: evaluation of patients for metastases.

PURPOSE: To compare the results of whole-body magnetic resonance (MR) imaging with staging based on computed tomographic (CT), dedicated MR imaging, and nuclear scintigraphic results as standard of reference. MATERIALS AND METHODS: Fifty-one patients with known malignant tumors were included in the study. Patients were placed on a rolling table platform capable of moving the patient rapidly through the isocenter of the magnet bore. The thorax and the abdomen were imaged by using fast breath-hold T2-weighted sequences in the transverse plane. After intravenous administration of a paramagnetic contrast agent, three-dimensional gradient-echo data sets were collected in five stations and covered the body from the skull to the knees. Location and size of cerebral, pulmonary, hepatic, and osseous metastases were documented by two experienced radiologists. Whole-body MR imaging findings were compared with results obtained at skeletal scintigraphy, CT, and dedicated MR imaging. RESULTS: The mean examination time for whole-body MR imaging was 14.5 minutes. All cerebral, pulmonary, and hepatic metastases greater than 6 mm in diameter could be identified with whole-body MR imaging. Small pulmonary metastases were missed with MR imaging, which did not change therapeutic strategies, but MR imaging depicted a single hepatic metastasis that was missed with CT. Skeletal scintigraphy depicted osseous metastases in 21 patients, whereas whole-body MR imaging revealed osseous metastases in 24 patients. The additional osseous metastases seen with MR imaging were confirmed at follow-up examinations but did not result in a change in therapy. Whole-body MR imaging performed on a per-patient basis revealed sensitivity and specificity values of 100%. CONCLUSION: Whole-body MR imaging for the evaluation of metastases compared well with the reference techniques for cerebral, pulmonary, and hepatic lesions. Whole-body MR imaging was more sensitive in the detection of hepatic and osseous metastases than were the reference techniques.

Rare expression of target antigens for immunotherapy on disseminated tumor cells in breast cancer patients without overt metastases.

Occult disseminated tumor cells are the major cause of relapse in patients with primary operable breast cancer but detection and characterization of these few cells is difficult. Applying immunohistochemistry, an immunomagnetic enrichment technique (IET) and immunocytochemistry (IC), we studied 58 breast cancer patients without overt metastases for the frequency of cytokeratin-positive (CK+) bone marrow (BM) cells coexpressing the epithelial adhesion molecule 17-1A (EpCAM) and c-erbB-2 and analyzed the primary tumor for these antigens as a strategy for additional immunotherapy. The primary tumors were analyzed for the target antigens by a pathologist. Dissemination of CK+ cells was studied in 4-6 x 10(6) BM cells by IC alone. For characterization of CK+ cells, 10-15 x 10(6) BM cells were incubated with microbeads coupled to antibodies detecting the target antigens, labelled cells were separated on selection columns and the positively (BM cells carrying the target antigen) and negatively (BM cells without target antigen) selected fractions were stained for CK+ cells. The effectiveness of these methods was confirmed in cell culture models. 17-1A was detected in all primary tumors and c-erbB-2 overexpression (2+, 3+) was found in 25/58 tissue samples. In total, analyzing 15-20 x 10(6) BM cells in each patient, the detection rate for CK+ cells in the BM was 69% (40/58 patients). Interestingly, analysis of the positive and negative enrichment fractions showed that the 17-1A antigen was coexpressed on CK+ cells in only 6 patients and c-erbB-2/CK+ cells were found in only one patient. Although 17-1A and c-erbB-2 were frequently detected in the primary tumor, these antigens were rarely expressed on CK+ BM cells. Whether the applied IET is not able to detect low amounts of these target antigens has to be clarified. Nevertheless, applying cell-cycle independent protocols in clinical trials requires careful elucidation of those patients who might benefit from these therapies.

Rare expression of epithelial cell adhesion molecule on residual micrometastatic breast cancer cells after adjuvant chemotherapy.

PURPOSE: Over the past 5 years, several clinical studies on a total of approximately 2500 patients have shown that the immunocytochemical detection of occult metastatic tumor cells in bone marrow (BM) at primary surgery provides important prognostic information in breast cancer (e.g., Ref 13 ). Here, we evaluated whether these cells can survive first-line chemotherapy and express epithelial cell adhesion molecule (Ep-CAM), recently suggested as promising target for immunotherapeutic interventions in breast cancer. EXPERIMENTAL DESIGN: A total of 62 patients with node-negative and -positive breast cancer but without distant metastases (Tumor-Node-Metastasis stage M(0)) was treated with two or more courses of various forms of adjuvant chemotherapy (e.g., cyclophosphamide-methotrexate-5-fluorouracil, anthracyclines). After chemotherapy, BM was aspirated from the upper iliac crest and analyzed for the presence of tumor cells. A first cohort of 34 BM aspirates was enriched for tumor cells by Ficoll density gradient centrifugation, and 2-4 x 10(6) mononuclear cells were analyzed per patient. The tumor cells were detected by anticytokeratin monoclonal antibody (Mab) A45-B/B3 and double labeled with Mab 3B10 against an Ep-CAM-epitope. The subsequent 27 BM aspirates were specifically enriched for Ep-CAM(+) cells using magnetic beads coupled to Mab 3B10, and tumor cells were identified by Fab fragments of Mab A45-B/B3 directly conjugated with alkaline phosphatase. RESULTS: After chemotherapy, 10 of 35 (28.6%) Ficoll-enriched BM samples contained cytokeratin-positive tumor cells. In total, 26 cytokeratin-positive cells were detected, but none of these cells coexpressed Ep-CAM. Even within the second cohort of 27 Ep-CAM-enriched BM samples, only 2 specimens (7.4%) harbored cytokeratin-positive cells costaining with the Ep-CAM antibody. CONCLUSION: Our results indicate that disseminated breast cancer cells in BM can survive first-line adjuvant chemotherapy. Ep-CAM expression is, however, restricted to a subset of these cells, which may limit the broad applicability of Ep-CAM as target for second-line adjuvant therapy in breast cancer.