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1.
Strahlenther Onkol ; 199(2): 121-130, 2023 02.
Article in English | MEDLINE | ID: mdl-36251031

ABSTRACT

PURPOSE: Cervical cancer remains a leading cause of cancer death in women. While immunotherapy has shown great success in combating cancer, the value of immunotherapy in cervical cancer is still only beginning to be explored. Thus, we performed a prospective analysis of patient blood and tumor samples at the beginning and end of conventional chemoradiation to assess changes in the immune cell and immunoreceptor compartments, and investigate if and when the addition of immunotherapy could be beneficial. METHODS: Patients with FIGO II-III cervical cancer receiving standard chemoradiation between January 2020 and December 2021 were included. We collected tumor and blood samples from patients before and at the end of therapy and analyzed immune cell composition and immune checkpoint receptor expression on both immune and tumor cells using multicolor flow cytometry. RESULTS: In all, 34 patients were eligible in the study period; 22 could be included and analyzed in this study. We found that chemoradiation significantly reduces T cell numbers in both tumors and blood, but increases macrophage and neutrophil numbers in tumors. Furthermore, we found that the percentage of immune checkpoint receptor PD­1 and TIGIT-expressing cells in tumors was significantly reduced at the end of therapy and that CD4 and CD8 memory T cell populations were altered by chemoradiation. In addition, we observed that while PD-L1 expression intensity was upregulated by chemoradiation on blood CD8 cells, PD-L1 expression frequency and the expression intensity of antigen-presenting molecule MHC­I were significantly reduced on tumor cells. CONCLUSION: Our data demonstrate that chemoradiation significantly alters the immune cell composition of human cervical tumors and the expression of immune checkpoint receptors on both lymphocytes and tumor cells. As our results reveal that the percentage of PD­1+ CD8 cells in the tumor as well as the frequency of PD-L1-expressing tumor cells were reduced at the end of therapy, neoadjuvant or simultaneous anti-PD­1 or anti-PD-L1 treatment might provide better treatment efficiency in upcoming clinical studies.


Subject(s)
Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/therapy , CD8-Positive T-Lymphocytes , Chemoradiotherapy , Immunotherapy/methods , Tumor Microenvironment
2.
Sci Rep ; 12(1): 2057, 2022 Feb 08.
Article in English | MEDLINE | ID: mdl-35136099

ABSTRACT

Molecular diameters are an important property of gases for numerous scientific and technical disciplines. Different measurement techniques for these diameters exist, each delivering a characteristic value. Their reliability in describing the flow of rarefied gases, however, has not yet been discussed, especially the case for the transitional range between continuum and ballistic flow. Here, we present a method to describe gas flows in straight channels with arbitrary cross sections for the whole Knudsen range by using a superposition model based on molecular diameters. This model allows us to determine a transition diameter from flow measurement data that paves the way for generalized calculations of gas behaviour under rarefied conditions linking continuum and free molecular regime.

3.
Strahlenther Onkol ; 194(11): 965-974, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30112692

ABSTRACT

PURPOSE: For endometrial cancer (EC), clinical and pathological risk factors are taken to triage patients and estimate their prognosis. Lymph node involvement (pN+), lymphovascular space involvement (LSVI), grading, age of the patients, and T classification are internationally accepted parameters for treatment decisions. MATERIALS AND METHODS: Studies on adjuvant radiation, chemotherapy, and chemoradiation are discussed against the background of risk stratification and clinical decision-making in early-to-advanced stage endometrial cancer. Recent publications on adjuvant treatment in high-risk disease and its implications for the patients with regard to expected oncologic benefit and treatment-related toxicity are discussed. RESULTS: Surgery is the mainstay of treatment of EC patients. Well-differentiated tumors and early disease (FIGO IA) should be followed up without further treatment. In FIGO I stage without risk factors, VBT remains the standard treatment after surgery. FIGO I, II patients with one or more risk factors (MI ≥ 50%, Grading[G]3, age >60 years, LVSI) benefit from external beam radiotherapy (EBRT) in terms of survival. There are no data of acceptable quality demonstrating that chemotherapy is superior to radiation in locally advanced carcinomas. Therefore, even in locally advanced disease (FIGO III, IV), EBRT remains the standard of care after surgery. EBRT contributes to the very low rate of local relapses and better DFS in these patients and should not be replaced by chemotherapy only. Whether and which subgroups of patients benefit from an additional (concomitant and/or adjuvant) chemotherapy in terms of disease-free survival remains a controversial issue. The recently published PORTEC-3 trial could not create clear evidence. With a high rate of isolated tumors cells and micrometastases in the specimens, the increasing use of unvalidated sentinel concepts in endometrial cancer raises more questions with regard to indications for adjuvant treatment. In the future, integrated genomic characterization of tumors might be helpful for treatment individualization in the adjuvant setting.


Subject(s)
Chemoradiotherapy, Adjuvant , Chemotherapy, Adjuvant , Endometrial Neoplasms/therapy , Radiotherapy, Adjuvant , Age Factors , Endometrial Neoplasms/pathology , Evidence-Based Medicine , Female , Humans , Lymphatic Metastasis/pathology , Neoplasm Grading , Neoplasm Micrometastasis/pathology , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Neoplastic Cells, Circulating , Prognosis , Risk Factors , Triage
4.
Breast Cancer Res Treat ; 168(3): 739-744, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29335922

ABSTRACT

PURPOSE: Mastectomy is the standard procedure in patients with in-breast tumor recurrence (IBTR) or breast cancer after irradiation of the chest due to Hodgkin's disease. In certain cases a second breast conserving surgery (BCS) in combination with intraoperative radiotherapy (IORT) is possible. To date, data concerning BCS in combination with IORT in pre-irradiated patients are limited. This is the first pooled analysis of this special indication with a mature follow-up of 5 years. METHODS: Patients with IBTR after external beam radiotherapy (EBRT; treated in two centers) for breast cancer were included. Patients with previous EBRT including the breast tissue due to other diseases were also included. IORT was performed with the Intrabeam™-device using low kV X-rays. Clinical data including outcome for all patients and toxicity for a representative cohort (LENT-SOMA scales) were obtained. Statistical analyses were done including Kaplan-Meier estimates for local recurrence, distant metastasis and overall survival. RESULTS: A total of 41 patients were identified (39 patients with IBTR, 2 with Hodgkin`s disease in previous medical history). Median follow-up was 58 months (range 4-170). No grade 3/4 acute toxicity occurred within 9 weeks. Local recurrence-free survival rate was 89.9% and overall survival was 82.7% at 5 years. Seven patients developed metastasis within the whole follow-up. CONCLUSIONS: BCS in combination with IORT in IBTR in pre-irradiated patients is a feasible method to avoid mastectomy with a low risk of side effects and an excellent local control and good overall survival.


Subject(s)
Breast Neoplasms/surgery , Breast/surgery , Neoplasm Recurrence, Local/surgery , Radiotherapy, Adjuvant/methods , Adult , Aged , Breast/pathology , Breast/radiation effects , Breast Neoplasms/pathology , Breast Neoplasms/radiotherapy , Combined Modality Therapy/adverse effects , Disease-Free Survival , Female , Humans , Intraoperative Care , Mastectomy , Mastectomy, Segmental/adverse effects , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy
5.
HNO ; 65(4): 328-336, 2017 Apr.
Article in German | MEDLINE | ID: mdl-27878599

ABSTRACT

BACKGROUND: According to international standards, determination of acoustic reflex thresholds (ART) is one of the established objective measurements in the diagnostic workup of central auditory processing disorders (CAPD). However, there is still no evidence for the significance of ART in CAPD diagnosis. PATIENTS AND METHODS: This study tested 57 children with proven CAPD and 50 healthy children (control group) with regard to group differences in mean ART (sine tones or bandpass-filtered noise). Additionally, it was investigated whether there were group differences between the mean dissociations of ART for sine tones or bandpass filtered noise. RESULTS: Neither ipsi- nor contralaterally were significant clinically relevant group differences (p < 0.050) between the mean ART of children with and without CAPD found. After Bonferroni correction, a significant group difference in the percentage of non-triggered reflexes was only observed with left-sided contralateral 2 kHz stimuli. Concerning the number of dissociations ≥20 dB, no significant group differences (p < 0.050) were detected either ipsi- or contralaterally (Fisher's test). CONCLUSION: The results of the study seem to indicate no clinically relevant ability of ART measurements to distinguish between children with and without CAPD. This renders the benefit of ART measurements for CAPD diagnosis questionable.


Subject(s)
Hearing Tests/methods , Language Development Disorders/diagnosis , Language Development Disorders/physiopathology , Reflex, Acoustic , Acoustic Stimulation , Child , Female , Humans , Language Development Disorders/classification , Male , Reproducibility of Results , Sensitivity and Specificity , Sensory Thresholds
6.
Bone Marrow Transplant ; 49(9): 1217-22, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25000458

ABSTRACT

We examined the course and the prevalence of a high fear of cancer recurrence (FCR) in patients undergoing allogeneic PBSC transplantation (hematopoietic SCT (HSCT)) before HSCT (N=239), 100 days after (n=150, and 12 months after allogeneic HSCT (n=102). The Fear of Progression Questionnaire-Short Form (FoP-Q-SF), the EORTC Quality of Life Questionnaire, and the Hospital Anxiety and Depression Scale were used. Pre-HSCT 36% of patients, 100 days after HSCT 24% of patients, and 1 year after HSCT 23% of patients fulfilled the criteria for high FCR (FoP-Q-SF cutoff=34). Being married (b=2.76, P=0.026), female gender (b=4.45, P<0.001) and depression (b=4.44, P<0.001) were significantly associated with FCR at baseline. One hundred days after HSCT, depression significantly predicted FCR (b=6.46, P<0.001). One year following HSCT, female gender (b=6.61, P=0.008) and higher depression were (b=4.88, P=0.004) significant predictors for FCR. Over the three assessment points, patients with high FCR had a significantly lower quality of life compared to patients with low FCR in physical functioning (P=0.019), role functioning (P=0.003), emotional functioning (P<0.001), cognitive functioning (P=0.003), social functioning (P<0.001) and global quality of life (P<0.001). Our data provide evidence that FCR is a prevalent problem in patients with hematological malignancies and has a significant adverse impact on health-related quality of life.


Subject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Adolescent , Adult , Aged , Female , Hematologic Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prospective Studies , Quality of Life , Transplantation, Homologous , Young Adult
7.
Histol Histopathol ; 27(4): 507-14, 2012 04.
Article in English | MEDLINE | ID: mdl-22374728

ABSTRACT

The carbohydrate molecules Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA), Lewis Y (LeY) and Thomsen-Friedenreich antigen (TF) are known to mediate the adhesion between tumor cells and endothelium. They are used as serum markers in diagnosis and treatment in a broad spectrum of human carcinomas, but their expression profile and role in the development of cervical cancer remains unclear. The aim of this study was to investigate the expression of SLeX, SLeA, LeY and TF in normal cervical squamous epithelium, cervical dysplasia and cervical cancer. Slides of paraffin-embedded tissue were fixed and incubated with monoclonal antibodies against SLeX, SLeA, LeY and TF. Immunohistochemical staining was evaluated by using a semi-quantitative score (IRS Score). We found a significant difference of SLeA expression in invasive cervical cancer compared to normal epithelium (p=0.006) and all grades of dysplasia (p=0.002). The expression of SLeX in normal epithelium was less intense than in carcinoma in situ (p=0.036). Staining for LeY showed the weakest results of the investigated markers. Significant differences were found when normal epithelium was compared to CIN I (p=0.011), to CIN II (p=0.013) and to invasive cervical cancer (p=0.005). For TF, significant differences were found in normal epithelium compared to CIN I (p=0.011), CIN II (p=0.013) and compared to invasive cervical cancer (p=0.005). This is the first study on the expression of SLeA, SLeX, LeY and TF in normal cervical endothelium, cervical dysplasia, carcinoma in situ and invasive cervical cancer. Further studies and higher numbers are desirable.


Subject(s)
Biomarkers, Tumor/metabolism , Cervix Uteri/pathology , Oligosaccharides/metabolism , Uterine Cervical Dysplasia/pathology , Uterine Cervical Neoplasms/pathology , Antigens, Tumor-Associated, Carbohydrate/metabolism , CA-19-9 Antigen , Cervix Uteri/metabolism , Epithelial Cells/metabolism , Epithelial Cells/pathology , Female , Humans , Immunoenzyme Techniques/methods , Lewis Blood Group Antigens/metabolism , Sialyl Lewis X Antigen , Uterine Cervical Dysplasia/metabolism , Uterine Cervical Neoplasms/metabolism
9.
J Microsc ; 230(Pt 2): 224-32, 2008 May.
Article in English | MEDLINE | ID: mdl-18445151

ABSTRACT

The conformational transition of alpha-helix-rich cellular prion protein (PrP(C)) to an isomer with high beta-sheet content is associated with transmissible spongiform encephalopathies. With the ultimate long-term goal of using imaging techniques to study PrP aggregation, we report the results of initial experiments to determine whether PrP molecules could be visualized as single molecules, and if the observed size corresponded to the calculated size for PrP. The investigation of single molecules, and not those embedded into larger aggregates, was the key in our experimental approach. Using atomic force microscopy (AFM) as an imaging method, the immobilization of recombinant histidine (His)10-tagged PrP on mica was performed in the presence of different heavy metal ions. The addition of Cu2+ resulted in an enhanced PrP immobilization, whereas Ni2+ reduced coverage of the surface by PrP. High-resolution data from dried PrP preparations provided a first approximation to geometrical parameters of PrP precipitates, which indicated that the volume of a single PrP molecule was 30 nm3. Molecular dynamics simulations performed to complement the structural aspects of the AFM investigation yielded a calculated molecular volume of 33 nm3 for PrP. These experimentally observed and theoretically expected values provide basic knowledge for further studies on the size and composition of larger amyloidal PrP aggregates, PrP isoforms or mutants such as PrP molecules without octarepeats.


Subject(s)
Microscopy, Atomic Force/methods , Prions/chemistry , Prions/ultrastructure , Aluminum Silicates/chemistry , Amyloid/chemistry , Amyloid/ultrastructure , Animals , Cattle , Metals, Heavy , Models, Molecular , Prions/genetics , Protein Folding , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/ultrastructure
10.
Laryngorhinootologie ; 2007 Jan 26.
Article in German | MEDLINE | ID: mdl-17253339

ABSTRACT

BACKGROUND: Stapedius muscle reflexes (SMR) are among the objective procedures which are used in the diagnostics of auditory processing disorders (APD). The significance of SRM for APD-diagnosis is open up to now. METHOD: Twenty-six children (8 - 10 years) with diagnosed APD and a control group of 17 children the same age were examined in order to determine whether differences with regard to the mean SMR (sine tones or band pass noise) exist between groups. In addition, differences between groups were investigated regarding the mean difference between the reflex thresholds for sine tones and the thresholds for band pass noises. RESULTS: Significant differences between groups existed in the mean value ipsilateral with 500 Hz, 1 kHz, 4 kHz and low bandpass noise as well as contralateral with 500 Hz. The contralateral measurements using sine tones (500 Hz, 1 kHz, 2 kHz and 4 kHz) showed reflex thresholds of about 100 dB only in the APD group. The results of the remaining types of stimulation showed a more or less distinctive area of overlap between the APD-group and the control group without the possibility of definite classification to a particular group. Group differences in the mean value with regard to the reflex thresholds for sine tones and the thresholds for band pass noises appeared only in low frequency stimuli. However, the area of overlap between the APD group and the control group in other frequencies was very large. CONCLUSION: Elevated thresholds measured in contralateral SMRs seem to support the assumption of APD. In contrast, the results of SMRs using ipsilateral measurements as well as low or high pass filtered noises contribute little toward diagnosing an APD. This applies identically to the difference between the reflex thresholds on sine tones and the thresholds on band-pass noises.

11.
Histol Histopathol ; 22(2): 169-76, 2007 02.
Article in English | MEDLINE | ID: mdl-17149689

ABSTRACT

OBJECTIVE: The endometrium expresses estrogen (ER) and progesterone receptor (PR), which are related to autocrine and paracrine processes that respond to estrogen and progesterone. Therefore, the aim of this study was to evaluate the distribution pattern of ERalpha, ERbeta, PR-A and PR-B with monoclonal antibodies in normal human endometrial tissue. STUDY DESIGN: Human endometrial tissue was obtained from 84 premenopausal and 11 postmenopausal patients and immunohistochemically analysed with monoclonal antibodies against ERalpha, ERbeta, PR-A and PR-B. RESULTS: ERalpha, PR-A and PR-B declined significantly (p<0.001, p<0.05, p<0.05 respectively) in glandular epithelium from proliferative to late secretory phase. The ERbeta immunohistochemical reaction showed a similar significant declining pattern (p<0.05), although the staining intensity was lower than that of ERalpha. While ERalpha, ERbeta and PR-B decrease significantly in atrophic endometrial tissue compared to proliferative endometrium, a significant up-regulation of PR-A was observed compared to late secretory phase (p<0.05). CONCLUSION: ERalpha, ERbeta, PR-A and PR-B were expressed in normal human endometrium with a cyclical variation during the menstrual cycle. In normal postmenopausal endometrial tissue, a down-regulation of ERalpha, ERbeta and PR-B occurs with a subsequent higher expression of PR-A. These results show the presence of steroid receptors in human epithelium, indicating that these cells respond to estrogen and progesterone, thus playing a significant role in endometrial physiology.


Subject(s)
Endometrium/metabolism , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Receptors, Progesterone/metabolism , Atrophy/pathology , Biomarkers/metabolism , Endometrium/pathology , Female , Humans , Immunoenzyme Techniques , Menstrual Cycle/physiology , Premenopause
12.
J Mol Histol ; 37(1-2): 43-52, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16670820

ABSTRACT

During human pregnancy the placenta produces a variety of proteins like steroid hormones and their receptors that are responsible for the establishment and ongoing of the feto-placental unit. Inhibins are dimeric glycoproteins, composed of an alpha-subunit and one of two possible beta-subunits (beta (A) or beta (B)). Aims of the present study were the determination of the frequency and tissue distribution patterns of the inhibin/activin subunits in human placental tissue of normal pregnancies and pregnancies complicated with fetal growth restriction (IUGR). Slides of paraffin embedded placental tissue were obtained after delivery from patients diagnosed with IUGR (n = 6) and normal term placentas (n = 8). Tissue samples were fixed and incubated with monoclonal antibodies inhibin/activin-subunits -alpha, -beta (A), -beta (B). Intensity of immunohistochemical reaction on the slides was analysed using a semi-quantitative score and statistical analysis was performed (P<0.05). A significant lower expression of the inhibin-alpha subunit in IUGR extravillous trophoblast compared to normal pregnancies was observed, while the inhibin-alpha immunostaining was significantly upregulated in syncytiotrophoblast. Additionally, a significant down-regulation of inhibin-beta (B) subunit in extravillous trophoblast cells in IUGR syncytiotrophoblast cells was demonstrated. A co-localisation of inhibin-alpha and the beta-subunits was also observed, suggesting a production and secretion of intact inhibin A and inhibin B. Although the precise role of these inhibin/activin subunits in human placenta and IUGR pregnancies is still unclear, they could be involved in autocrine/paracrine signalling, contributing to several aspects like angiogenesis and tissue remodelling.


Subject(s)
Activins/metabolism , Fetal Growth Retardation/metabolism , Inhibins/metabolism , Trophoblasts/metabolism , Adult , Biomarkers/metabolism , Female , Fetal Growth Retardation/pathology , Fluorescent Antibody Technique, Indirect , Humans , Immunoenzyme Techniques , Inhibin-beta Subunits/metabolism , Pregnancy , Signal Transduction , Trophoblasts/pathology , Young Adult
13.
Acta Neurochir (Wien) ; 147(5): 533-40; discussion 540-1, 2005 May.
Article in English | MEDLINE | ID: mdl-15806332

ABSTRACT

BACKGROUND: The prototype of a 3D ultrasound navigation system, with a trackable 4- to 8-MHz phased-array ultrasound probe was used in syrinx-surgery. The aim of this study was to evaluate the advantages offered by 3D ultrasound and navigation in syringomyelial surgery. METHODS AND MATERIALS: After laminectomy, with a free-handed tilt of the ultrasound probe, the 3D volume of the target area is acquired within 15 seconds. The data are visualized after reconstruction in an axial, coronal, and sagittal view, offering the possibility of ultrasound-based guided surgery. RESULTS: Based on the intraoperative volume information, it was possible to navigate with the 3D ultrasound images in all cases. The orientation and image quality with respect to resolution, spatial information, and the identification of anatomical structures facilitated the surgery in all seven cases. The navigation tool, with a length of 12 cm and a tip diameter of 1 mm, was simple to place into the surgical site. The availability of an up-to-date 3D-image resulted in less interruption of the surgical procedure, with no need to repeatedly fill the cavity with sterile saline for new ultrasound acquisitions. New ultrasound images were only required if shift occurred. The coronal and "trajectory-plane" views, offer additional information about the syrinx cavity. The target borders are easier to determine and orientation in separated cavities was possible. Particularly in syringomyelial surgery it was helpful to determine the surface point of the syrinx to place the myelotomy or insert a catheter. CONCLUSION: 3D ultrasound offers the advantages of visualizing the third dimension of the target. For orientation and border determination navigation within the 3D ultrasound volume is very helpful and can take place with the ultrasound probe out of the way. Any disruption in the surgical procedure is minimized by not having to repeatedly fill the cavity with a sterile saline solution, there are fewer difficulties with image orientation because of new image adjustments.


Subject(s)
Imaging, Three-Dimensional/methods , Neurosurgical Procedures/methods , Spinal Cord/diagnostic imaging , Surgery, Computer-Assisted/methods , Syringomyelia/diagnostic imaging , Ultrasonography/methods , Cervical Vertebrae/anatomy & histology , Cervical Vertebrae/surgery , Feasibility Studies , Humans , Magnetic Resonance Imaging , Neurosurgical Procedures/instrumentation , Predictive Value of Tests , Reproducibility of Results , Spinal Cord/pathology , Spinal Cord/surgery , Surgery, Computer-Assisted/instrumentation , Syringomyelia/pathology , Syringomyelia/surgery , Ultrasonography/instrumentation
14.
Childs Nerv Syst ; 21(2): 156-60, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15095106

ABSTRACT

INTRODUCTION: Malignant intracranial ependymomas in childhood have a poor prognosis, supratentorial ependymomas have the poorest clinical course with a survival rate after 5 years of 45%. The most important prognostic factor in these cases is a radical operation, which cannot usually, however, prevent relapse. CASE REPORT: We demonstrate the case of a large malignant ependymoma of the left cerebral hemisphere in a child who has so far lived for 16 years without relapse after an extensive but uncomplicated left-sided hemispherectomy. The patient has also shown an improvement in her preoperative neurologic deficits. Her epilepsy, which was difficult to manage preoperatively, has been completely eliminated. She went to a special school for handicapped children and now works there. She does not need any help in handling everyday activities. CONCLUSION: This case shows the significance of complete tumor resection in malignant ependymomas, which may, under certain circumstances, lead to lasting tumor control.


Subject(s)
Ependymoma/surgery , Hemispherectomy/methods , Supratentorial Neoplasms/surgery , Female , Humans , Infant , Longitudinal Studies , Magnetic Resonance Imaging/methods , Staining and Labeling/methods , Supratentorial Neoplasms/pathology , Tomography, X-Ray Computed/methods , Treatment Outcome
15.
Zentralbl Neurochir ; 64(2): 65-70, 2003.
Article in English | MEDLINE | ID: mdl-12838474

ABSTRACT

INTRODUCTION: Expression of hemagglutinin antigen of influenza virus (HA) by the murine colon carcinoma cell line (CT-26) produces systemic immunization against tumor challenges in the cecum, liver and lungs but not in the brain of BALB/c-mice. Immunization with IL-4 expressing CT-26 cells inhibits lung metastases formation. The purpose of our study was to examine the effects of HA or IL-4 expression on brain metastases formation. METHODS: Using selective internal carotid artery injections, brain metastases formation of HA or IL-4 expressing CT-26 cells with and without subcutaneous pre-immunization was evaluated in Balb/c mice. RESULTS: Systemic pre-immunization with HA or IL-4 expressing tumor cells cannot protect against brain metastases, while the local, intracerebral expression of HA or IL-4 inhibits the growth of hematogenous brain metastases. CONCLUSION: Pre-immunization with HA or IL-4 expressing tumor cells did produce systemic immunity against liver and lung metastases but not against brain metastases. Local, intracerebral expression of HA or IL-4 prevents from cerebral metastases formation in an animal model.


Subject(s)
Brain Neoplasms/prevention & control , Brain Neoplasms/secondary , Hemagglutinin Glycoproteins, Influenza Virus/biosynthesis , Interleukin-4/biosynthesis , Animals , Brain Neoplasms/immunology , Carotid Artery, Internal , Colonic Neoplasms/immunology , Colonic Neoplasms/metabolism , Female , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Immunization , Injections, Intra-Arterial , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Survival Analysis , Tumor Cells, Cultured
17.
Nervenarzt ; 73(10): 967-71, 2002 Oct.
Article in German | MEDLINE | ID: mdl-12376885

ABSTRACT

The case of a patient suffering from renal cell carcinoma and recurrent brain metastases shows how the survival period can be significantly prolonged by a combination of stereotactically guided percutaneous single-dose convergent beam irradiation and surgery. This 58-year-old man's left kidney was completely excised because of a renal cell carcinoma. After 18 months and 25 months, respectively, a right frontal brain metastasis was operated on. In the next 7 years, biannual MRI checks were carried out which successively showed five different brain metastases, each of which was immediately subjected to single-dose stereotactic irradiation (median dosage: 20 Gy prescribed to the 80% isodose). In the following 2 years, operations were carried out on two metastases which could not be treated by radiation because of their considerable size and partial compression of the ventricle. In the next 3 years, four more brain metastases were subjected to single-dose stereotactic irradiation. There were no metastases in the other organs. At present, the patient is in good clinical condition and mobile. A negative prognosis is usually delivered for patients suffering from renal cell carcinoma and brain metastasis. However, in individual cases, the survival period can be significantly prolonged by regular MRI examinations and a combination of neurosurgery and single-dose stereotactic irradiation.


Subject(s)
Brain Neoplasms/secondary , Carcinoma, Renal Cell/secondary , Cerebral Cortex/surgery , Kidney Neoplasms/surgery , Radiosurgery , Brain Neoplasms/diagnosis , Brain Neoplasms/surgery , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/surgery , Cerebellar Neoplasms/diagnosis , Cerebellar Neoplasms/secondary , Cerebellar Neoplasms/surgery , Cerebral Cortex/pathology , Follow-Up Studies , Frontal Lobe/pathology , Frontal Lobe/surgery , Humans , Kidney Neoplasms/diagnosis , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/diagnosis , Neoplasm Recurrence, Local/surgery , Nephrectomy , Reoperation
18.
Schmerz ; 16(5): 404-11, 2002 Sep.
Article in German | MEDLINE | ID: mdl-12235505

ABSTRACT

INTRODUCTION: Neuralgias of the face, especially trigeminal neuralgia and glossopharyngeal neuralgia are indications for surgical interventions after failed medical therapy. In contrast to other forms of headache or atypical facial pain, where surgical measures are considered to be contraindicated, percutaneous procedures or microvascular decompression are able to produce immediate and longstanding pain relief. Careful preoperative evaluation is essential to confirm the clinical diagnosis and to rule out other causes as multiple sclerosis or tumors afflicting the cranial nerves. The following study will summarize the common surgical techniques and their role considering a mechanism-based therapy as well as document long-term results of these measures. METHODS: Between 1977 and 1997 316 thermo-controlled radiofrequency trigeminal rhizotomies (TK) and 379 microvascular decompressions (MVD) were performed in our hospital to treat trigeminal neuralgia; additional 6 MVDs for glossopharyngeal neuralgia and one MVD of the intermediate facial nerve were carried out. Questionnaires were sent out to all patients still living in 1981, 1982, 1992 and 1998. For all other patients, interviews with relatives or the general practitioners were conducted. A retrospective analysis of postoperative pain relief was performed using Kaplan-Meier curves at the latest follow-up. Additionally 80 patients underwent careful quantitative sensory testing with Von-Frey-hairs. RESULTS: 225 patients who underwent microvascular decompression and 206 with radiofrequency trigeminal rhizotomies were further analyzed. There was a 50% risk for pain recurrence two years after radiofrequency rhizotomy. On the other hand 64% of patients who underwent microvascular decompression remained painfree 20 years postoperatively. Patients with microvascular decompression without sensory deficit were painfree significantly longer than patients with postoperative hypesthesia. DISCUSSION: Etiology and pathogenesis of facial neuralgias are far from understood despite several hypotheses. Based on current models there is no explanation for the immediate pain relief especially after microvascular decompression. Some authors even discuss surgical trauma as the only cause for postoperative pain relief.


Subject(s)
Facial Neuralgia/surgery , Diagnosis, Differential , Facial Neuralgia/diagnosis , Humans , Neurosurgical Procedures , Recurrence , Retrospective Studies , Rhizotomy , Risk Factors , Trigeminal Nerve/surgery
19.
Acta Neurochir (Wien) ; 144(5): 433-43, 2002 May.
Article in English | MEDLINE | ID: mdl-12111499

ABSTRACT

BACKGROUND AND PURPOSE: In clinically non-functional pituitary macroadenomas, prospective follow-up magnetic resonance imaging (MRI) was conducted after transsphenoidal surgery both to study the changes of the sellar contents at the post-operative site over time and to assess the amount of residual adenoma tissue. METHODS: A total of 50 patients with clinically non-functional pituitary macroadenomas were treated by transsphenoidal tumour resection and were examined by MRI before and directly after surgery (early MR) and 3 months (intermediate MR) and 1 year after surgery (late MR). Changes in the sellar contents over time and the degree of tumour excision were studied on T1-weighted enhanced and unenhanced scans. All patients underwent complete neuro-ophthalmological and endocrinological assessments before and 3 months after surgery. For the interpretation of the post-operative images the results of the endocrinological examinations after surgery were also taken into account. RESULTS: The maximum size of tumour extension on coronal T1-weighted images ranged from 1.2 cm to 5.0 cm (mean 2.3 cm). Despite tumour resection, early post-operative images still showed a persistent mass in the sella in 83% that was usually caused by post-operative haemorrhage, fluid collection and implanted fat material. However, rapid improvement in visual symptoms was noted in 89%. Changes in the sellar region at the early post-operative site markedly hindered the interpretation of MR images for detecting residual tumour tissue, which was suspected in half of the patients (1 intrasellar, 13 suprasellar, and 11 parasellar). Regression of the post-operative mass in the sella was present 3 months after surgery, resulting in a 50% change in the volume of the coronal sellar extension, which also improved the reliability in interpreting the post-operative MR images. On the intermediate MR images residual tumour tissue was detected in 30% of the patients (4 intrasellar, 2 suprasellar and 9 parasellar). Because the suprasellar mass descended over time, an increasing rate of tumour remnant within the sella was seen 3 months following surgery. Before surgery the pituitary gland was visible superiorly or posterosuperiorly to the macroadenomas in 35 patients. However, at the early post-operative site the remaining gland was only visible in 12 patients. Under the condition that endocrinological function tests confirmed adequate hormonal function, the remaining gland was detectable by MRI in 36 patients 3 months after surgery. CONCLUSION: Delayed regression of the sellar contents after transsphenoidal surgery of pituitary macroadenomas was demonstrated by this prospective MR study. Owing to the changes at the post-operative site, it was difficult to interpret early post-operative images and detect residual adenoma tissue. With respect to the delayed regression of the sellar contents, the interpretation of post-operative images for detection of residual adenoma was improved 3 months after surgery. At this time, residual adenoma tissue was found in 30% of clinically non-functional macroadenomas, mostly at the parasellar and, after descent from the suprasellar space, at the intrasellar site.


Subject(s)
Adenoma/surgery , Pituitary Neoplasms/surgery , Sella Turcica/pathology , Adenoma/pathology , Adult , Aged , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm, Residual/pathology , Pituitary Neoplasms/pathology , Treatment Outcome
20.
Minim Invasive Neurosurg ; 45(2): 91-6, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12087506

ABSTRACT

High frequency stimulation of the basal ganglia has gained much interest during the last years. Based on the reevaluation of the results of functional neurosurgery for movement disorders from Leksell's group, pallidotomy as lesional procedure was the first functional operation that underwent a renaissance for the treatment of movement disorders. The work by Benabid and Siegfried who carried out thalamic high frequency stimulation to suppress tremor, the knowledge about deep brain stimulation (DBS) for the treatment of chronic pain as well as better understanding in basal ganglia physiology and the development of reliable stimulation hardware led to an increasing number of centers worldwide who currently apply high frequency DBS for different movement disorders. In the present review the current status of DBS for movement disorders is presented and the results with high frequency stimulation targeted at different brain areas are summarized.


Subject(s)
Basal Ganglia/surgery , Electric Stimulation Therapy/methods , Movement Disorders/therapy , Subthalamic Nucleus/surgery , Ventral Thalamic Nuclei/surgery , Animals , Humans , Movement Disorders/surgery
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