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The intention of this retrospective analysis with follow-up was to assess results after decompressive or additional stabilising operations in the clinical setting of degenerative lumbar spinal stenosis.74 patients, operated upon from 1995 to 2001, were investigated clinically, radiologically and with questionnaire score 1 to 8 years (mean 2.5) postoperatively. All data were compared and evaluated with the preoperative findings. The results of the group with decompressive operations were compared with those for the group with additional stabilising operations.The patients with stabilising operations showed an improvement of 78.3% on the visual analogue scale and of 76.1% on the Oswestry score. The patients with decompressive operations showed an improvement of 91.7% on the visual analogue scale and of 75.0% on the Oswestry score. The difference between the two groups was not significant. There was a poorer outcome for previously operated patients or patients with a prolonged course of disease.The choice of the operative treatment with regard to spinal stenosis requires a differentiated preoperative diagnostic procedure in accord with the respective living situation and age of the patients. Instability in terms of degenerative spondylolisthesis, lumbar scoliosis as well as intraoperatively recognised or generated instability has to be additionally stabilised with an instrumented fusion in regard to the functional aspect of the stenosis.

Topotecan has demonstrated exceptional central nervous system penetration as well as radiosensitizing properties in glioblastoma xenografts [Chastagner et al., Int J Radiat Oncol Biol Phy 50: 777-782, 2001]. This phase I trial was performed to determine the maximum tolerated dose and the recommended dose of topotecan continuous infusion administered together with concomitant radiotherapy in patients with glioblastoma.A total of 20 patients were treated in this trial. Twenty one day topotecan continuous infusion was escalated from 0.3 mg/m2/d in increments of 0.1 mg/m2/d and cohorts of 3-6 patients until maximum tolerated dose was reached; Three-dimensional (3d) conformal radiotherapy was applied concurrently twice daily with a fraction size of 1.75 Gy up to 57.75 Gy total dose. Three additional cycles of maintenance topotecan chemotherapy were scheduled.Fifty-three courses were performed in 5 dose levels (0.3 mg/m2/d: 12 cycles, 0.4 mg/m2/d: 6 cycles, 0.5 mg/m2/d: 10 cycles, 0.6 mg/m2/d: 6 cycles, 0.7 mg/m2/d: 19 cycles). Maximum tolerated dose was reached at dose level 5 (0.7 mg/m2/d), because 3/7 patients suffered from dose limiting toxicity. These were febrile sinusitis, bacterial sepsis and grade 4 thrombocytopenia. Neutropenia of grade 4 was encountered in 2 cycles (0.5 and 0.7 mg/m2/d). Response data were available in 17 patients, 3 of which (18%) achieved partial remission, 12 (71%) stable disease throughout the observation period and 2 (11%) progressive disease.The recommended dose for further trials will be 0.6 mg/m2/d topotecan administered as 21 days continuous infusion in combination with accelerated 3d conformal radiation.

The aim of the study was to analyze the results of stereotactic radiotherapy using a linear accelerator in patients with brain metastases. We quantified the following clinical parameters: tumor response and tumor control after therapy, survival, and side effects. Results of the treatment were compared with those from traditional treatment strategies such as surgery and whole brain irradiation. Sixty patients with brain metastases (80 lesions, 36 men and 24 women, mean age 57 years) were treated with stereotactic radiotherapy. The mean follow-up time was 13 months.Stereotactic radiotherapy is an important option in the treatment strategy for patients with brain metastases. In comparison to whole brain irradiation, stereotactic radiotherapy achieved a higher local tumor control with a lower rate of side effects. In comparison to surgery, stereotactic radiotherapy has the advantages of shorter treatment time and lower treatment-related morbidity and mortality.

The aim of this study was to evaluate the prognostic value of SPECT imaging using the amino acid analog 3-[(123)I]iodo-L-alpha-methyltyrosine (IMT) in patients with gliomas.One hundred fourteen consecutive patients with newly diagnosed gliomas were examined by IMT SPECT (low-grade glioma, n = 12; anaplastic astrocytoma or oligodendroglioma, n = 46; glioblastoma, n = 56). Seventy-one of these patients had undergone tumor resection 4-6 wk before SPECT imaging (group A). Forty-three patients with unresectable tumors were examined after stereotactic biopsy (group B). IMT uptake at the site of the tumor was assessed visually and quantified relative to a contralateral reference region (IMT uptake ratio). After IMT SPECT, all patients were treated with conformal radiotherapy. The median follow-up time was 27 mo.In group A, focal IMT uptake at the resection site was visible in 52 of 71 patients (73%). Median survival was only 13 mo in these patients, whereas median survival was reached in patients without focal IMT uptake (P = 0.02). Furthermore, the intensity of IMT uptake significantly correlated with survival: patients with an IMT uptake ratio1.7 were at a 4.6 times higher risk of death than were patients with a lower IMT uptake (P0.001). The IMT uptake ratio remained a significant prognostic factor when age and grading were included in a multivariate model. In contrast, IMT uptake did not correlate with survival in group B (P = 0.95).In patients with unresectable high-grade gliomas, IMT uptake appears not to correlate with the biologic aggressiveness of tumor cells. Nevertheless, the clear association between focal IMT uptake after tumor resection and poor survival suggests that IMT is a specific marker for residual tumor tissue. Therefore, IMT SPECT is expected to become a valuable tool for the planning and monitoring of local therapeutic modalities.

To evaluate overall survival, local tumor control and cosmetic outcome after breast-conserving surgery followed by radiotherapy without boost irradiation.In a retrospective study 270 breast cancer patients were treated with breast conserving surgery combined with a homogenous radiation of the tumor bearing breast up to a total dose of 56 Gy without local boost irradiation. Mean follow-up was 48 months. Local tumor control, side effects, cosmetic results and contentment with treatment were assessed using physical examinations and interviews based on a standardized questionnaire.Cause-specific survival at 5 years after treatment was 88.3%, actuarial disease-free survival at 5 years was 76.1%. Within 23 to 78 months after treatment 12 patients suffered from ipsilateral breast recurrence. The actuarial freedom from local recurrence (single tumor manifestation) was 96.8% at 5 years after treatment, 89% at 10 years. The occurrence of local failures was not significantly correlated to tumor size, margins, grading, nodal status, age or lymphangiosis. 15.6% of the patients developed distant metastases. In all patients treatment was performed without interruption. Side effects were predominantly of mild degree, no severe side effects were detected. 73% of physicians and 81% of patients scored their cosmetic outcome as excellent or good. 93% of patients would again decide in favor of this procedure. Whereas use of adjuvant chemotherapy as well as subcutaneous reconstruction of breast tissue did not significantly affect breast cosmesis, analysis demonstrated impaired cosmetic results related to a larger breast size.The data of this study show that tumor control achieved by breast conserving surgery in combination with a radiation technique up to a total dose of 56 Gy which omits boost irradiation is within the range of literature data. Side effects of the therapy were tolerable. The treatment displayed a good compatibility with tolerable side effects and good cosmetic results.

Clinical investigation of a potential relationship between the polarographically measured tumor oxygenation and the p53 status in patients with squamous cell carcinoma of the head and neck.In 99 patients with mostly advanced, histologically proven squamous cell carcinoma of the head and neck we estimated the classical tumor parameters (TNM stage, histological grading) the immunohistochemical p53-overexpression (DO-7) and the tumor oxygenation status (Eppendorf pO2 Histograph). The tumor volume and the hemoglobin concentration were evaluated simultaneously.No statistically significant difference could be detected between immunohistological p53-positive (p53or = 10% stained cells) and p53-negative tumors (p5310% stained cells) regarding both the median pO2 and the relative frequency of valuesor = 5 mm Hg. Moreover, no statistically relevant differences could be seen between both p53-groups considering the hemoglobin concentration, the TNM stage, the histological grading and the tumor volume.Our data imply that there is no association between p53-overexpression and tumor hypoxia in head and neck carcinomas. However, this is not necessarily in contradiction to experimental or clinical data that confirmed a relationship between hypoxia and p53-mediated increased malignancy of tumor cells in other tumor entities. The comparable oxygenation status of p53-positive and p53-negative tumors in our study is associated with an analogous clinical tumor aggressiveness of both groups. That could be caused by a hypoxia related but p53-independent selection of tumor cells with a more malignant phenotype in head and neck carcinomas. However, further research is needed to prove this possible relationship.

Radiotherapy became an important component in the treatment of brain gliomas. The aim of this study is to analyse several advantages of the three-dimensional conformal radiation therapy in comparison with a two-dimensional conventional technique and to present the clinical results of 43 patients with brain gliomas treated according to a three-dimensional planning.Between January 1994 and December 1995, 43 patients with malignant brain gliomas (WHO III and IV) were treated in our department according to a three-dimensional treatment planning. The patients received a total irradiation dose of 60 Gy, 2 Gy/day, 5 days/week. The rate of survival was analysed in relation with the known prognostical factors: histology, Karnofsky index, age, resection status. In 10 patients a three-dimensional treatment planning was compared with a conventional two-dimensional planning: the volume of the normal brain tissue irradiated to high dose levels (95% isodose) and the normal tissue complication probability (NTCP) for the brain by Kutcher and Lyman were comparatively analysed.The survival rate for the whole group was 14 months. The histology of the tumor, age, Karnofsky index and resection status were important prognostical factors. The three-dimensional planning allows a 15 to 20% reduction in the volume of normal brain tissue irradiated to high dose levels (95% isodose). The NTCP is significantly lower using the three-dimensional technique (range 0.03% to 13%), in comparison with the two-dimensional conventional technique (range 0.1% to 26%). The value of NTCP increases with tumor volume.Concerning the tumor control and survival rate, the three-dimensional treatment planning shows no advantages compared to the standard conventional methods. The main advantage of the three-dimensional treatment planning is the possibility to spare normal brain tissue. The possibility to integrate mathematical models in the evaluation of the therapy could give this technique new dimensions.

We report on a novel protocol involving iridium 192 high-dose-rate brachytherapy and follow-up of up to 130 months in patients with prostatic carcinoma. Using regional anesthesia, five to seven hollow needles are placed within the prostate by perineal puncture under ultrasound guidance. A 9-Gy prostate dose is applied followed by 30 min of hyperthermia (since 1991). This treatment is repeated once after 7 days; 2 weeks later, 18 x 2-Gy external beam radiation (small-field prostate) is added as percutaneous dose saturation. Since 1984 we have treated 40 patients with this protocol. Local tumor control was achieved by means of prostatic biopsy at 18 months after therapy and determination of prostate-specific antigen (PSA) values in about 70% of the patients; after a mean follow-up period of more than 6 years (16-130 months), 80% of the patients show either no evidence of disease or stable disease. We therefore conclude that iridium 192 high-dose-rate brachytherapy is a useful alternative in the treatment of localized prostate cancer in patients who are not eligible for radical prostatectomy.

Water-filtered infrared-A-radiation (IR/A-HT) can be used to heat superficial malignant tumors. A prospective multicenter phase I-II study was conducted to evaluate toxicity and efficacy of IR/A-HT combined with external beam radiotherapy (RT).From December 1991 to June 1994, a total of 53 patients with 58 malignant lesions were entered in the study. There were 14 primary, 36 recurrent and 8 metastatic tumors which were located in the head and neck region (14), chest wall (31), abdominal wall (2) and the extremities (11). The mean tumor volume was 100 cm3. IR/A-HT was applied 1 to 2 times per week with up to 3 IR/A-HT-radiators directly before or after external RT for 1 hour at 40.5 to 44 degrees C. Temperatures were controlled at various locations at the skin surface and invasively at depth.IR/A-HT was well tolerated: in 31 (53%) lesions acute (pain, pulse or blood pressure changes, increased skin reaction etc.) and in 25 (43%) chronic side-effects (atrophy, telangiectasis, fibrosis etc.) were noted; usually the toxicity was minor and temporary. At 3 months FU, 32 (55%) lesions achieved a local CR and 19 (35%) a PR; at 12 months FU, 25 (43%) had persistent CR; 16 patients (18 lesions) were deceased and 3 (4 lesions) not yet in FU. In univariate analysis the following prognostic factors for CR at 3 or 12 months FU were found: Karnofsky, metastatic status, tumor size, total RT-dose, thermal parameters T min(av) and T mean. For acute toxicity maximum temperature Tmax(av) was prognostically decisive. Significant differences were also found when considering the "quality of the HT-application". The microwave technique was superior to the infrared-A-HT-technique with regard to the penetration depth of energy deposition.Water-filtered infrared-A-radiation can be safely and effectively applied to heat localized superficial tumors (up to 1 cm depth). To increase the area of HT application multiple infrared-A-radiators have to be combined. A multi-element-system is in progress.

Experimental data have shown that hypoxic areas in tumors can increase their malignant potential and reduce their sensitivity to chemotherapy and radiation treatment. Until now, the only incomplete data on the oxygenation of human tumors during therapy have been available.The distribution of partial pressure of oxygen in malignant head and neck processes was measured in four patients with lymph-node metastases by means of invasive computerized histography (system manufactured by Eppendorf). All patients received primary radiation treatment and chemotherapy with a two-week respite after 30 Gy and the first cycle of chemotherapy. The total dose consisted of 70 Gy in the tumor and two cycles of chemotherapy. Oxygen measurements were taken before the onset of treatment, before and after the respite, and after completion of treatment.In three of the four patients, we measured prominent hypoxic areas in the cancers with PO2 values less than 5 mmHg. The average value was between 12 and 46 mmHg. We were impressed by the observation that oxygenation appeared to improve in every cancer during the respite. Only the patient who showed good initial oxygenation without any measurable hypoxic fraction suffered a complete recurrence six weeks after the completion of therapy.Prominent areas of hypoxic tissue are present in human head and neck cancers. Radiation treatment and chemotherapy can alter the oxygenation. Further studies are required to investigate the significance of the oxygenation of human head and neck cancers and the changes occurring in it during different types of therapy in order to assess its clinical impact.

Since portal images taken with conventional X-ray films suffer from poor contrast and unsharpness due to the high energy of the radiation beam, scattered radiation, patient motion, and the large dimensions of the radiation source, comparison of portal images with simulation images is often difficult and time consuming. Therefore many efforts have been made to improve such images. The use of storage phosphors and electronic image post-processing provides a remarkable improvement of image quality with better delineation of anatomical landmarks in high contrast areas such as head, neck, and mediastinum, as well as in low contrast regions, i.e. abdomen and pelvis.

From 1971 to 1980, 639 patients with carcinoma of the cervix and 271 patients with endometrial cancer were treated in the Division of Radiation Therapy of the Medical School Hannover. In 606 patients radical radiation therapy was followed by routine surgery, 304 patients have been irradiated primarily due to the local spread of the tumor. The radiation therapy consisted of a combination of external beam and intracavitary therapy. In patients with carcinoma of the cervix the five-year survival was 92% for stage Ia, 78% for stage Ib, 67% for stage IIa, 47% for stage IIb, 20% for stage III and 7% for stage IV. In patients with endometrial cancer the five-year survival was 91% for stage I, 71% for stage II, 60% for stage III and 0% for stage IV. Severe complications, i.e., ureteral stricture or fistula occurred in 1% to 1.5% of the patients with cervix cancer and in 0.5% to 1% of the patients with endometrial cancer.

A retrospective analysis of 63 patients with malignant major salivary gland tumours treated between 1972 and 1988 is presented. In 54 patients the tumour was located in the parotid gland, in the remaining nine patients the tumour was located in the submandibular gland, 31 patients were treated for stage I to II disease, 32 patients for stage III to IV disease. All patients were irradiated postoperatively using 60 Co. 137 Cs photons or electrons of adequate energies. As basic techniques ipsilateral portals, a wedge pair of portals or parallel opposed fields were used. The target doses ranged between 45 and 70 Gy with fractions of three to five times 2 to 3 Gy weekly, dependent on postoperative status and stage. In 25% of the patients a local recurrence was evident after radiotherapy with 13% developing distant metastases. The five-year survival was 95% for stage I, 83% for stage II, 30% for stage III and 7% for stage IV. Additionally, the prognosis varied according to lymph node involvement, grading and microscopic or macroscopic residual disease.

Objective and design Atherosclerosis (ATH) is a chronic inflammatory disease that involves cascades of signaling events mediated by various effector proteins. Here we sought to determine if the expression of Wnt5a, a secreted glycoprotein, is altered in discrete regions of the arterial plaque. Methods Atherosclerotic plaque tissues from 14 human subjects undergoing elective carotid endarterectomy were used in this study. Immunohistochemistry and laser capture microdissection combined with quantitative real-time PCR were used to determine the expression of Wnt5a and Toll-like receptors (TLRs) in different sections of the arterial lesions. Atherosclerotic serum samples (n = 30) and serum from healthy subjects (n = 16) were quantified for Wnt5a using an enzyme-linked immunosorbent assay (ELISA). Results The data analysis revealed that Wnt5a transcripts and protein were elevated in advanced arterial lesions relative to less advanced arterial lesions; that Wnt5a expression correlated with the presence of TLR4 and TLR2 transcripts; and that the average amount of Wnt5a protein present in atherosclerotic patient serum was significantly higher compared to healthy controls. Conclusions This study is the first to provide evidence that the expression of Wnt5a increases as the disease progresses to a more advanced stage, and that this expression is coincident with that of TLR2 and TLR4. In addition, we found that the average Wnt5a levels in the serum of atherosclerotic patients are elevated relative to healthy controls, which is consistent with the hypothesis that Wnt5a plays a role in ATH.

Prior to a combined treatment with ionizing radiation and hyperthermia, 38 patients with superficial, semi-deep, and deep tumors received catheters for temperature measuring probes which were introduced under CT control. After having established a localization diagnosis and determined the angle for the puncture as well as the length of the puncture canal, a puncture needle containing a closed teflon catheter was introduced subsequent to local anaesthesia and puncture incision of the skin. None of the patients needed a general analgetic and sedative treatment. 10% of the patients presented a dislocation making necessary a reimplantation. Local infections at the catheter insertion point were observed in three cases, a phlegmonous inflammation was seen only in one patient who had undergone an immunosuppression by means of cytostatic drugs. In one patient a temporary bleeding led to a slight haemoglobin reduction which, however, did not require further therapeutic measures. The insertion of catheters for intratumoral temperature measurement was well tolerated by the patients. It could be performed in out-patients with good general condition and no further risk factors.

From 1973 through 1986, twelve patients suffering from carcinomas of the outer auditory canal were irradiated at the Radiologic Hospital of Essen. The five-year survival was 64% after postoperative irradiation and 0% after irradiation alone. Considering the data communicated by other authors, the following therapy recommendations can be deduced: early stages where bones or cartilages are not involved represent an indication for sole operation. These tumors can be successfully treated by sole radiotherapy, too. In case of greater tumors, combined surgery and postoperative radiotherapy is the most favorable method. Besides a high total dose (50 to 60 Gy for microscopic tumor residues, about 70 Gy for macroscopic tumor residues), a sufficiently great target volume has to be chosen which includes the ear, the temporal bone, the preauricular lymph nodes and the angle of mandible. To prevent bone and cartilage necroses, it is recommended to restrict the individual doses to 1.8 to 2 Gy each.