Medizin - Open Access LMU - Teil 14/22 Archiv

The processing of emotional facial expression is a major part of social communication and understanding. In addition to explicit processing, facial expressions are also processed rapidly and automatically in the absence of explicit awareness. We investigated 12 healthy subjects by presenting them with an implicit and explicit emotional paradigm. The subjects reacted significantly faster in implicit than in explicit trials but did not differ in their error ratio. For the implicit condition increased signals were observed in particular in the thalami, the hippocampi, the frontal inferior gyri and the right middle temporal region. The analysis of the explicit condition showed increased blood-oxygen-level-dependent signals especially in the caudate nucleus, the cingulum and the right prefrontal cortex. The direct comparison of these 2 different processes revealed increased activity for explicit trials in the inferior, superior and middle frontal gyri, the middle cingulum and left parietal regions. Additional signal increases were detected in occipital regions, the cerebellum, and the right angular and lingual gyrus. Our data partially confirm the hypothesis of different neural substrates for the processing of implicit and explicit emotional stimuli. Copyright (c) 2007 S. Karger AG, Basel.

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3-5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI -4.6 to 10.8%, p > 10.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined. Copyright (C) 2008 S. Karger AG, Basel.

Background: Patients with metastatic breast cancer (MBC) are increasingly exposed to anthracyclines and taxanes either during treatment of primary breast cancer or during initial therapy of metastatic disease. The combination of gemcitabine and carboplatin was therefore investigated as an anthracycline- and taxane-free treatment option. Patients and Methods: MBC patients previously treated with chemotherapy were enrolled in a multicenter phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) i.v. on days 1 and 8) and carboplatin (AUC 4 i.v. on day 1) applied every 3 weeks. Results: Thirty-nine patients were recruited, and a total of 207 treatment cycles were applied with a median of 5 cycles per patient. One complete response and 11 partial responses were observed for an overall response rate of 31% (95% CI: 17-48%). Twelve patients (31%) had stable disease. Median time to progression was 5.3 months (95% CI: 2.6-6.7 months) and median overall survival from start of treatment was 13.2 months (95% CI: 8.7-16.7 months). Grade 3/4 hematological toxicity included leukopenia (59%/5%), thrombo-cytopenia (26%/23%) and anemia (10%/0%). Nonhematological toxicity was rarely severe. Conclusion: Combination chemotherapy with gemcitabine and carboplatin is an effective and generally well-tolerated treatment option for intensively pretreated patients with MBC. Due to a considerable incidence of severe thrombocytopenia it would be reasonable to consider starting gemcitabine at the lower dose level of 800 mg/m(2). Copyright (c) 2008 S. Karger AG, Basel.

Objective: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. Methods: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m(2) twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. Results: A median of 3 treatment cycles (range 1-36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5-45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7-45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. Conclusion: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended. Copyright (C) 2008 S. Karger AG, Basel.

Imatinib has had marked impact on outcomes in chronic myelogenous leukemia (CML) patients for all stages of the disease and is endorsed by international treatment guidelines as the first line option. Although imatinib is highly effective and well tolerated, the development of resistance represents a clinical challenge. Since the most frequently identified mechanism of acquired imatinib resistance is bcr-abl kinase domain point mutations, periodic hematologic, cytogenetic, and molecular monitoring is critical throughout imatinib therapy. Once cytogenetic remission is achieved, residual disease can be monitored by bcr-abl transcript levels as assayed by reverse transcription polymerase chain reaction (RT-PCR). Detection of bcr-abl mutants prior to and during imatinib therapy can aid in risk stratification as well as in determining therapeutic strategies. Thus, mutation screening is indicated in patients lacking or losing hematologic response. Moreover, search for mutations should also be performed when a 3-log reduction of bcr-abl transcripts is not achieved or there is a reproducible increase of transcript levels. In patients harboring mutations which confer imatinib resistance, novel second line tyrosine kinase inhibitors have demonstrated encouraging efficacy with low toxicity. Only the T315I bcr-abl mutant has proved totally resistant to all clinically available bcr-abl inhibitors. Strategies to further increase the rates of complete molecular remissions represent the next frontier in the targeted therapy of CML patients.

Background: Irinotecan-based second-line chemotherapy of metastatic colorectal cancer (CRC) is effective, it might, however, be contraindicated in cases of severe liver dysfunction due to advanced liver metastases. Case Report: A 57-year-old woman with diffuse CRC liver metastases showed progressive disease on first-line treatment with capecitabine and oxaliplatin (XELOX). Chronic cholestasis and hyperbilirubinemia caused by advanced liver involvement prohibited second-line treatment with irinotecan-based chemotherapy. We initiated combined antibody treatment with cetuximab and bevacizumab. Results: Clinical performance status as well as laboratory parameters improved rapidly. Staging investigations after 8 weeks revealed a partial remission. Since bilirubin levels had returned to the upper limit of normal, therapy could be changed to standard irinotecan, 5-fluorouracil, folinic acid, and bevacizumab. Conclusion: Combined treatment with cetuximab and bevacizumab may be considered as an effective treatment option in patients who cannot be treated with standard chemotherapy regimens due to impaired liver metabolism of cytotoxic substances.

Background: Paravasation is a rare but severe complication of treatment with cytotoxic agents. Some anticancer drugs are considered to be of high toxicity (vesicant), some are merely irritant, and some are regarded as nearly non-toxic to healthy tissue as is the case with cyclophosphamide. Case Report: In this report, we present the first case of severe tissue damage caused by a paravasation of cyclophosphamide in a breast cancer patient receiving chemotherapy. Conclusion: Therefore, every attending oncological physician should be aware of the possibility of severe tissue damage as a consequence of cyclophosphamide paravasation.

Background: Due to an aging population the incidence of both cardiac and tumor-related illnesses is increasing. A problem may arise if radiotherapy is necessary in close anatomic proximity to an implantable cardioverter-defibrillator (ICD). These highly precise devices may respond to ionizing radiation with a loss of function or uncontrolled stimulation, with both effects being potentially life threatening. Available guidelines recommend the dose maximum to a pacemaker to be cumulative below 2 Gy. For most patients undergoing radiation therapy of the neck or of the chest this limit is exceeded, thus making a removal of the device and an implantation of an external ICD necessary. Case Report: A patient with severe cardiac problems underwent an implantation of an ICD. However, a recurrence of a laryngeal cancer was diagnosed. The irradiation dose after resection was 60 Gy to the tumor region and 50 Gy to the lymph nodes. Irradiation peakload to the ICD was calculated to be 2.5 Gy. This dose was verified with thermoluminescence measurements. The ICD was externally deactivated during the sessions of irradiation. Device checks demonstrated no malfunction. Conclusion: Even though the dose limits of the ICD of 2 Gy were exceeded, the device demonstrated a regular function during and after radiotherapy.

Background: The carbohydrate antigen 19-9 (CA 19-9) is currently the most widely used serum tumor marker in pancreatic cancer (PC). CA 19-9 pretreatment levels as well as CA 19-9 kinetics during systemic chemotherapy can provide prognostic information regarding survival of patients with metastatic PC. Case Reports: We report the clinical course of 2 patients with metastatic PC who underwent palliative chemotherapy with gemcitabine. Both patients showed a significant elevation of pretreatment CA 19-9 levels (7,505 and 150,000 U/ml, respectively), however, subsequently they experienced a highly significant reduction (> 90%) of CA 19-9 kinetics under gemcitabine chemotherapy. A good disease control and a clinical benefit response were achieved in both patients. Time to tumor progression was 30 weeks and 28 weeks, overall survival 14 months and 11 months, respectively. Conclusion: These data indicate that CA 19-9 kinetics under chemotherapy may possibly serve as a useful surrogate marker for time to tumor progression and survival in advanced PC.

Background: To perform lamellar keratolimbal allograft transplantation in a one- step procedure with a single graft, we investigated the feasibility of harvesting eccentric lamellar keratolimbal grafts from conventionally processed corneoscleral buttons using a manually guided microkeratome in conjunction with an artificial anterior chamber system. Methods: We used the Moria LSK- One microkeratome and the automated lamellar therapeutic keratoplasty ( ALTK) system ( Antony, France). Ten human donor eyes were used to obtain single- piece lamellar keratolimbal grafts. Specimens were processed for light and electron microscopy. Results: Eccentric keratolimbal grafts could be obtained from all human donor buttons. Grafts include a crescent- shaped limbal and a large corneal portion. No visible damage to the limbal region was discernible. Conclusion: Our data show that the LSK- One microkeratome in conjunction with the ALTK system allows harvesting eccentric keratolimbal grafts from donor corneoscleral buttons. Copyright (c) 2007 S. Karger AG, Basel.

Purpose: To compare and correlate imaging of classic subfoveal choroidal neovascularization (CNV) with noninvasive 3-dimensional imaging by the retinal thickness analyzer (RTA) to conventional fluorescein angiography (FA). Methods: A total of 29 eyes of 29 consecutive patients with predominantly classic CNV eligible for photodynamic therapy underwent FA and RTA imaging. The FA dimensions of the CNV were measured independently by two graders. With the RTA, masked to FA the size of the CNV itself as imaged in 3-dimensional reconstruction, the size of significantly thickened retina overlying the CNV and the maximum retinal thickness were measured. Results: The mean diameter of the CNV determined from 3-dimensional RTA reconstructions showed an excellent correlation with measurements from FA (r = 0.91, p < 0.001). The area of retinal thickening was by a mean of 0.7 mm in diameter larger and correlated moderately well with the size of the CNV on FA (r = 0.65, p < 0.001). In contrast, there was no correlation between the absolute retinal thickness and the CNV size on FA. Conclusions: Noninvasive quantitative mapping of predominantly classic CNV by RTA is feasible and also allows 3-dimensional measurement of the lesion itself. The results correlate well with FA assessment but visualize different properties of the disease. Copyright (c) 2007 S. Karger AG, Basel.

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >= 50% in eyes with high-risk characteristics. Pan-retinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level. Copyright (c) 2007 S. Karger AG, Basel.

Background: The implementation of automated techniques improves the workflow and quality of immuno-hematological results. The workflows of our university blood bank were reviewed during the implementation of an automated immunohematological testing system. Methods: Work impact of blood grouping and subgrouping, cross- matching and antibody search using the Immucor Galileo system was compared to the previous used standard manual and semi- automated methods. Results: The redesign of our workflow did not achieve a significant reduction of the specimen's working process time, the operator's time however was reduced by 23%. Corresponding results were achieved for blood grouping, Rhesus typing, antibody screen and for autocontrol when changing from two semi- automated to the Galileo system. Because of the higher sensitivity of the Immucor antibody detection system, the rate of the initial positive antibody screens rose from 4 to 6% Conclusion: The Immucor Galileo system automates routine blood bank testing with high reliability, specificity and higher sensitivity compared to our previous used standard manual and semi- automated methods.

Background: Psychoeducational interventions that provide disorder-related information in a goal-oriented and structured manner have been integrated in psychiatric and psychotherapeutic approaches. The present cognitive psychoeducational group programme for inpatients with affective disorders is based on a multidimensional functional illness concept which covers aspects of vulnerability, stressors and coping strategies. It covers information about the disorder and its treatment options, building up rewarding activities, cognitive restructuring and relapse prevention. Materials und Methods: This programme was developed and modified at the University of Munich, Department of Psychiatry (LMU). A feasibility study was set up in a follow-up single group design and analyses of variance (ANOVAs) were performed. A total of 231 patients participated in 46 groups. Results: 125 patients evaluated the effectiveness of the programme and its treatment strategies. The group programme was widely accepted among patients that were pharmacologically and psychotherapeutically treated: more than three quarters of the patients rated its contents to be informative, helpful and applicable to everyday living. Conclusions: Inpatients with affective disorders may already benefit from a structured group programme if it takes into account their cognitive and motivational deficits. The group leaders' didactic and psychotherapeutic strategies as well as the patients' exchanging ideas with each other play a central role. In the course of further investigations the programme was differentiated for patients with major depression or bipolar disorders.