[Possibilities and perspectives of quality management in radiation oncology]. / Möglichkeiten und Perspektiven des Qualitätsmanagements in der Radioonkologie.

The medical discipline radiation oncology and radiation therapy (treatment with ionizing radiation) has developed rapidly in the last decade due to new technologies (imaging, computer technology, software, organization) and is one of the most important pillars of tumor therapy. Structure and process quality play a decisive role in the quality of outcome results (therapy success, tumor response, avoidance of side effects) in this field. Since 2007 all institutions in the health and social system are committed to introduce and continuously develop a quality management (QM) system. The complex terms of reference, the complicated technical instruments, the highly specialized personnel and the time-consuming processes for planning, implementation and assessment of radiation therapy made it logical to introduce a QM system in radiation oncology, independent of the legal requirements. The Radiation Center Hamburg (SZHH) has functioned as a medical care center under medical leadership and management since 2009. The total QM and organization system implemented for the Radiation Center Hamburg was prepared in 2008 and 2009 and certified in June 2010 by the accreditation body (TÜV-Süd) for DIN EN ISO 9001:2008. The main function of the QM system of the SZHH is to make the basic principles understandable for insiders and outsiders, to have clear structures, to integrate management principles into the routine and therefore to organize the learning processes more effectively both for interior and exterior aspects.

Neuropsychological function in high-risk breast cancer survivors after stem-cell supported high-dose therapy versus standard-dose chemotherapy: evaluation of long-term treatment effects.

BACKGROUND: Studies on cognitive functioning in breast cancer patients point out that a subset of women exhibit chemotherapy-related neuropsychological impairment. Thereby, high-dose therapy may elevate the risk of cognitive dysfunctions. The primary purpose of the study was to evaluate the impact of high-dose versus standard-dose chemotherapy on the late neuropsychological outcome in randomized assigned high-risk breast cancer survivors. Next to focusing prevalence, function specificity and extent of cognitive impairment, the question as to whether doses-dependent group differences occur was investigated. PATIENTS AND METHODS: Twenty-four high-dose and 23 standard-dose patients 5 years, on average, after treatment underwent a comprehensive neuropsychological assessment. In addition, 29 early-stage breast cancer patients matched for age, education and time since treatment were recruited as a comparison group. RESULTS: Global cognitive impairment was observed in 8% of high-dose versus 13% of standard-dose compared with 3% of early-stage breast cancer patients. Compared with normative data, all patient groups performed worse on one attention subtest measuring the simple reaction time (P < 0.001 in each case). By contrast, no significant between-group differences on the late neuropsychological outcome were found. CONCLUSIONS: Five years after treatment, standard-dose patients were slightly, but not significantly, more impaired in cognitive performance than high-dose patients.

[Treatment results following breast-conserving therapy in primary breast cancer]. / Behandlungsergebnisse nach brusterhaltender Therapie des primären Mammakarzinoms.

OBJECTIVE: To evaluate mono-institutional results concerning tumor free survival, overall survival, local tumor control and rate of distant metastasis following breast-conserving therapy. PATIENTS AND METHODS: Retrospectively, 274 breast cancer patients who were treated between 1990-1997 in our institution were analysed. The whole breast was homogeneously irradiated (2.0 Gy to 50 Gy), followed by a boost of 10-16 Gy to the tumor bed. Mean follow-up was 55 months. Overall survival, local tumor control and rate of distant metastasis were analysed. RESULTS: Cause-specific survival at 5 years after treatment was 93 %. Within 3 to 60 months following treatment, 18 (7 %) patients suffered from ipsilateral breast recurrence. 24 (9 %) patients developed contralateral carcinoma. Survival from local recurrence (single manifestation) was 78 % at 5 years after treatment, 20 % at 7 years. Occurrence of local failures was significantly correlated to receptor status, contralateral carcinoma, distant metastasis and surgical technique and not to tumor size, margins, grading, nodal status, age or lymphangiosis. 9 % of the patients developed distant metastases, predominantly bone metastases (71 %). Survival from distant metastasis was 64 % at 5 years, 10 % at 7 years. Occurrence of distant metastasis was significantly correlated to grading, tumor size, receptor status, lymphangiosis or local recurrence. CONCLUSION: Our institutional results show that tumor free survival, overall survival, local tumor control and distant failure rate achieved by breast conserving therapy are within the range of literature data.

Comparative evaluation of pulmonary lactoferrin and lysozyme immunoreactivity for the postmortem diagnosis of death due to sepsis.

To determine whether lactoferrin (LF) and lysozyme (LZ) can be used as immunohistochemical postmortem markers of sepsis, pulmonary tissue sections from autopsy cases of sepsis-related fatalities (n = 13) and control cases of non-septic fatalities (n = 14) were evaluated for differences in leucocytic immunoreactivity. LF and LZ were investigated in paraffin sections using the AEC technique. The immunohistochemical expression of both markers was scored, evaluating the quantity of immunopositive cells and the intensity of the intracellular immunoreactivity. There was a statistically significant association between an enhanced expression of LF on pulmonary leucocytes in sepsis-related fatalities in contrast to non-sepsis cases (P < 0.001), whereas no such difference could be observed for LZ immunoreactivity between the two study groups. Pneumonic tissue alterations had no significant influence on LF and LZ immunoreactivity, thus suggesting differences between the degranulation of these non-specific antibacterial agents in local and systemic inflammatory processes. While the variability of LZ immunoreactivity, possibly reflecting a non-specific release from lysosomes according to the length of the postmortem interval, limits its application to the postmortem diagnosis of sepsis, the immunohistochemical detection of an enhanced expression of LF can contribute to the postmortem discrimination between sepsis and non-septic fatalities.

Post-mortem markers of sepsis: an immunohistochemical study using VLA-4 (CD49d/CD29) and ICAM-1 (CD54) for the detection of sepsis-induced lung injury.

The up-regulation of different adhesion molecules such as VLA-4 (CD49d/CD29) and ICAM-1 (CD54) on the pulmonary endothelium and leukocytes, is a key event in sepsis-induced lung injury leading to inflammatory tissue alterations. The value of VLA-4 and ICAM-1 as micromorphological post-mortem markers for the detection of sepsis-induced lung injury, was evaluated in a semiquantitative immunohistochemical study. VLA-4 was strongly expressed on intravascular, interstitial and intra-alveolar leukocytes in sepsis-associated fatalities, whereas in non-septic fatalities an irregular weak immunoreactivity was observed on interstitial leukocytes and no positive immunohistochemical expression was detected on intravascular or intra-alveolar leukocytes. ICAM-1 was strongly expressed on endothelial cells of the pulmonary microvasculature and on pulmonary macrophages and lymphocytes in sepsis-associated fatalities. In contrast, an infrequent weak immunohistochemical reaction for ICAM-1 was found on pulmonary endothelium and on perivascular leukocytes in non-septic fatalities. Based on the results of the present preliminary study, VLA-4 and ICAM-1 can be considered as useful immunohistochemical post-mortem markers of sepsis.

Immunohistochemical expression of E-selectin in sepsis-induced lung injury.

The vascular endothelium controls leukocyte extravasation into tissue by the induction and modulation of endothelial cell adhesion molecules, such as E-selectin (CD62E). E-selectin is not expressed by non-stimulated endothelium, but is activated by cytokines and initiates neutrophil recruitment in sepsis-induced lung injury. The aim of the present study was to assess the value of the immunohistochemical expression of endothelial E-selectin for the post-mortem differentiation between death due to sepsis and death due to other causes. The immunohistochemical expression of E-selectin was investigated in lung specimens obtained at autopsy from sepsis-associated fatalities (n = 6), possible sepsis-associated fatalities (n = 7), non-sepsis group I (death due to unnatural causes, e.g. trauma, electrocution, drowning, hanging n = 17) and non-sepsis group II fatalities (death due to natural causes, e.g. myocardial infarction, intracerebral bleeding n = 7). E-selectin was detected in paraffin sections using the ABC technique and the expression was scored semiquantitatively by evaluating the intensity and incidence of positively stained endothelium of the interstitial pulmonary microvasculature. E-selectin was strongly expressed in all cases of the definite sepsis group, in 29% of the possible sepsis-associated fatalities and in only 4% of the cases in the non-sepsis groups I and II. In comparison to all other study groups, E-selectin expression in the definite sepsis group differed significantly (p < 0.05). Cases with inflammatory and mechanical lung tissue alterations from the control groups showed no positive immunohistochemical reaction for E-selectin; therefore, false positive results should not be expected in non-sepsis cases. Our findings suggest that the immunohistochemical detection of an intense expression of E-selectin in lung tissue may prove to be a valuable diagnostic tool in the forensic post-mortem elucidation of death due to sepsis.

Additive cytotoxic effect of cisplatin and X-irradiation on human glioma cell cultures derived from biopsy-tissue.

PURPOSE: Investigation of the in vitro cytotoxic effect of X-rays, either alone or combined with cisplatin on early passage cell cultures derived from human glioblastoma multiforme biopsy tissue. MATERIALS AND METHODS: Fresh tumour specimens from four patients were processed to cell cultures. The U373 glioma cell line was used as a reference. Early passage cell cultures were X-irradiated (0-8 Gy) either alone or in combination with cisplatin (0.5-1 microgram/ml). Cell survival was determined by either clonogenic assay or the colorimetric MTT assay. Survival curves were generated and mathematically analysed using the linear quadratic model, to obtain the radiosensitivity parameters alpha, beta, and SF2, i.e., the Surviving Fraction after 2 Gy. RESULTS: Two patient-derived glioma cell cultures and the U373 cell line showed rather high SF2 values of 0.61-0.72 in the clonogenic assay, indicating relative high radiation resistance. Cisplatin alone (1 microgram/ml) reduced cell survival by 10-30% (n = 4). When combined with irradiation, a clear additive cytotoxic effect of cisplatin was demonstrated by the unaltered value of the alpha-parameter for reproductive cell death. CONCLUSION: Cisplatin exerted an additive rather than radiosensitising cytotoxic effect in uncharacterised patient derived glioma cell cultures.