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A Dietz

Publications and source records attributed to A Dietz.

At least 73 records · Page 4Linked to original sources
PubMed2000

[Prognostic value of hemoglobin level for primary radiochemotherapy of head-neck carcinomas].

The pretherapeutic hemoglobin level (Hb) has been postulated to constitute a prognostic marker for outcome after primary chemoradiation of patients with advanced cancer of the head and neck. However, this hypothesis has not been tested systematically in large study samples. In the years 1992-1997, 125 patients with advanced head and neck cancer (stages III/IV UICC) were treated with primary chemoradiation in two different prospective multicentric trials, 62 patients in trial A (phase II, 1992-1995), and 63 in trial B (phase III, 1995-1997). Beside initial Hb, other pretherapeutic parameters with potential prognostic relevance were assessed and correlated with clinical outcome after 43-months follow-up: total tumor volume (TTV; calculated in initial CT scans), tumor oxygenation (polarographic measurements with Eppendorf histography), TNM, tumor localization, age, and performance status. The evaluation of the clinical end points (progression-free and overall survival and local tumor control) revealed that Hb and TTV were independent parameters with strong predictive character of outcome after primary chemoradiation in both trials (n = 125). Bivariate analysis showed < median (13.5 g/dl) a hazard ratio of 2.1 (P = 0.002) for Hb; and > median (98 ml) a Hazard ratio of 2.0 (P = 0.006) for TTV. Severe anemia (Hb < 10 g/dl) was an adverse factor in three patients. Hypoxia was associated with poorer initial therapeutical response but was not predictive of clinical outcome. Furthermore, tumor oxygenation showed no correlation with Hb. The other parameters examined failed to show prognostic significance. Our results indicate a high prognostic value of initial Hb for outcome after primary chemoradiation in advanced head and neck cancer and imply a therapeutic benefit of Hb substitution or erythropoietin administration. We propose to test this in randomized clinical trials.

Adult↗
PubMed2000

[Quality assurance in ENT tumor surgery].

BACKGROUND AND OBJECTIVE: Quality control is of special importance in head and neck oncology since the quality of medical care constitutes a vital parameter for the diseased patient. In contrast to other medical specialties, no quality assurance program for head and neck cancer patients has yet been established in Germany. Therefore, a survey was conducted to assess the quality assurance instruments that are in use today in otorhinolaryngology-head and neck (ORL-HNS) centers. PATIENTS AND METHODS: In a nationwide survey, questionnaires were sent out to 146 German ORL-HNS departments (the return rate was 75%). RESULTS: 56% of all departments apply dedicated quality assurance processes, and 38% have appointed a formal quality assurance officer. Interdisciplinary oncological conferences are held in the vast majority of all departments with the participation of radiation oncologists in 86 (78%), medical oncologists in 84 (76%), diagnostic radiologists in 82 (74%), and pathologists in 73 (66%). Morbidity-mortality conferences are held in seven departments (6%). A standardized follow-up of oncological patients is carried out in 95 units (86%), and 53 departments use computer-assisted data bases to organize their follow-up data (48%). A wide variety of documentation systems is in use throughout the country: 78 units (71%) offer formal follow-up to their oncological patients. CONCLUSIONS: This survey documents a wide-spread interest in quality assurance procedures. Many individual efforts are being undertaken. However, no uniform quality assurance or auditing system is currently in use in Germany nor is a commonly accepted data base available. The ability to offer oncological follow-up within the national social security system is generally considered indispensable for the maintenance of high-quality oncological care in ORL-HNS departments.

Germany↗
PubMed2000

Repeatability and prognostic impact of the pretreatment pO(2) histography in patients with advanced head and neck cancer.

PURPOSE: The purpose of this study was to evaluate the repeatability and the predictive relevance of the pretreatment pO(2) histography on the survival of patients with advanced head and neck cancer. PATIENTS AND METHODS: From July 1995 to August 1998, polarographic pO(2) measurements of lymph node metastases before therapy were performed in altogether 60 patients with histologically proven squamous cell carcinoma of the head and neck using the Eppendorf histograph. Forty-one of 60 patients were treated with an accelerated-hyperfractionated radiotherapy regimen with or without simultaneous chemotherapy as part of a multicenter phase III study. In 23 of 60 patients, two repeated independent measurements of the same tumor were performed with a time interval of approximately 24 h between the two measurements. RESULTS: The multivariate analysis revealed the fraction of pO(2) values </=2.5 mmHg as the only significant prognostic factor for the survival (P=0.05) in the 41 study patients. No correlation was found between tumour oxygenation and the volume of the measured lymph node metastases or the haemoglobin concentration. The coefficient of variation of the repeated measurements representing the assay variability was 57-68% of the total variation. CONCLUSION: Our data support the concept of the relevance of the pretreatment tumour hypoxia for the prognosis of patients with head and neck cancer after fractionated radiotherapy. Because of the relative poor repeatability of the pO(2) histography and the small patient number, further studies are required to confirm this finding and to evaluate the most relevant oxygenation parameter for clinical endpoints.

Adult↗
PubMed2000

Oxygenation of advanced head and neck cancer: prognostic marker for the response to primary radiochemotherapy.

Recent clinical studies suggest that the degree of tumor oxygenation may be predictive of the response of radiation therapy for cancer. In an exploratory investigation of cervical lymph node metastases in 27 patients with advanced squamous cell carcinoma of the oropharynx and hypopharynx, this relationship was investigated by means of oxygen measurements with an Eppendorf PO (2) histograph. The measurements were made before the start of radiation therapy and after the first week of therapy. Clinical response was evaluated 6 weeks after the completion of therapy. Before therapy, marked hypoxia was observed in the lymph node metastases, with a mean PO (2) value of 16.1 +/- 8.2 mm Hg and a hypoxic fraction (PO (2) < 10 mm Hg) of 56.4% +/- 20.0%. After the first week of radiation (9 Gy) there was a general reoxygenation (DeltaPO (2) = 5.0 +/- 10.1 mm Hg, P < 0.05; Deltahypoxic fraction = -11.3% +/- 31.3%, P = 0.11). A relationship between the degree of reoxygenation and tumor response was not observed. Patients without at least partial lymph node response (n = 8) showed poorer pretherapeutic oxygenation (PO (2) mean = 11.1 +/- 2.9 mm Hg) than those who responded to the therapy (n = 19, PO (2) mean = 18.2 +/- 8.8 mm Hg). In this investigation of a defined set of patients with advanced carcinoma of the oropharynx and hypopharynx, we found that pretherapeutic oxygenation data are predictive for the therapeutic response to radiation therapy or radiochemotherapy.

Adult↗
PubMed2000

Immunomodulating effects of surgical intervention in tumors of the head and neck.

The immunomodulating effect of primary surgical intervention in 33 patients with squamous cell carcinoma of the oral cavity, pharynx, and larynx was analyzed prospectively. An operation time of longer than 7 hours was significantly associated with a decrease of total lymphocyte counts, CD4(+) T lymphocytes, and CD8(+) T lymphocytes. The CD4/CD8 ratio as a marker for the downregulation of the cellular immune response was slightly decreased but still in the normal range. CD4(+) lymphocyte counts increased within 7 days, and CD8(+) lymphocytes increased 4 weeks after the operation. The in vitro stimulation of the lymphocytes was impaired for 1 to 4 weeks. Release of interleukins, interferon-gamma, and tumor necrosis factor-alpha remained low despite the surgical trauma. The decreased lymphocyte counts, especially CD4(+) and CD8(+) lymphocytes, were significantly associated with duration of operation and volume of blood loss. Extension of trauma, age, type of anesthesia, and type of intensive care intervention were not associated with specific immunomodulating effects. However, these factors might be responsible for suppression of the immune system, which is expressed by lymphocyte depletion, lymphocyte dysfunction, and impaired upregulation of cytokine secretion.

Adult↗
PubMed2000

Prognostic assessment of sonography and tumor volumetry in advanced cancer of the head and neck by use of doppler ultrasonography.

OBJECTIVE: The objective of this trial was to examine the degree of tumor vascularity in lymph node metastases as depicted by computer-assisted color Doppler sonography and the tumor volumes associated with prognosis in carcinomas of the oropharynx and hypopharynx after primary radiochemotherapy. PATIENTS AND METHODS: In a prospective trial, 25 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx (stage IV UICC 1997) were treated with radiochemotherapy. The color Doppler findings were quantified with a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD). As important prognostic cofactor, total tumor volume (TTV) was calculated from CT sections and related to the degree of vascularity. RESULTS: Low CPD in neck metastases showed a correlation with better overall survival. A high-CPD group and a high-TTV group (median survival 10.1 months) were determined and were compared with all other CPD/TTV combinations (median survival 28.4 months); the difference in survival was significant (P = 0.002). CONCLUSION: The results indicate that high tumor vascularity in combination with high TTV indicates a particularly bad prognosis in patients treated with primary radiochemotherapy for head and neck cancer.

Adult↗
PubMed2000

Reduction in defibrillation threshold using an auxiliary shock delivered in the middle cardiac vein.

Defibrillation in the middle cardiac vein (MCV) has been shown to reduce ventricular defibrillation thresholds (DFTs). Low amplitude auxiliary shock (AS) from an electrode sutured to the left ventricle at thoracotomy have also been shown to reduce DFT if delivered immediately prior to a biphasic shock (between the ventricular RV and superior vena caval (SVC) electrodes). This study investigates the impact on DFT of an AS shock from a transvenously placed MCV lead system. A standard defibrillation electrode was positioned in the RV in eight anesthetized pigs (35-43 kg). A 50 x 1.8-mm electrode was inserted in the MCV through an 8 Fr angioplasty guide catheter. A 150-V (leading edge) monophasic AS was delivered (95 microF capacitor) from the MCV-->Can with three different pulse widths (3, 5, 7 ms). A primary biphasic shock (PS) (95 microF capacitor, phase 1: 44% tilt, 1.6-ms extension and phase 2: 2.5-ms fixed duration) was delivered from the RV-->Can +/- AS. The four configurations were randomized and DFTs (PS + AS) assessed using a modified binary search. Ventricular fibrillation (VF) was induced with 60 Hz AC followed 10 seconds later by the test shock. The DFTs were compared using repeated measures analysis of variance (ANOVA). All configurations incorporating AS produced significant (P < 0.05) reduction in the DFT compared to no AS (13.8 +/- 7.4 J). There was no difference in the efficacy of differing pulse widths (P > 0.05); 3 ms (11.0 +/- 5.4 J), 5 ms (11.5 +/- 6.0), and 7 ms (10.6 +/- 5.3 J). In conclusion, delivering an AS from a transvenous lead system deployed in the MCV reduces the DFT by 23% compared to a conventional RV-->Can shock alone.

Analysis of Variance↗
PubMed1999

Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head and neck carcinoma during simultaneous radiochemotherapy.

The kinetics of local drug uptake and metabolism of the anticancer drug 5-fluorouracil (5-FU) has been monitored by means of 19F nuclear magnetic resonance spectroscopy in 17 patients with neck tumors during concurrent radiochemotherapy. All of the patients underwent an accelerated hyperfractionated, concomitant-boost radiochemotherapy with 5-FU [600 or 1000 mg/m2 of body surface (b.s.)] and carboplatin (70 mg/m2 of b.s.). Serial 19F nuclear magnetic resonance spectra were obtained during and after the administration of 5-FU in a 15-T scanner with the use of a 5-cm diameter surface coil positioned on a cervical lymph node metastasis. Examinations were performed at day 1 of therapy and, in 13 patients, also after 43.5 Gy of irradiation at day 1 of the second chemotherapy cycle. Resonances of 5-FU and the catabolites 5,6-dihydro-5-fluorouracil (DHFU) and alpha-fluoro-beta-alanine (FBAL) were resolved in the tumor spectra. The median of the 5-FU and FBAL levels was significantly higher (more than 2-fold) at the second compared with the first examination, whereas the level of DHFU did not change. This effect could indicate an increased delivery of 5-FU into the interstitial space of the tumor in the course of the combined treatment, which would result in an enhanced exposure of the tumor cells to the drug. A potential mechanism for synergy between radio- and chemotherapy is discussed, but alternative mechanisms are also being considered. The findings indicate that a method is available to rationally address the design of dosing schedules in concurrent therapy regimens.

Adult↗
PubMed1999

[Predictive value of serum levels of basic fibroblast growth factor, vascular endothelial growth factor and matrix metalloproteinase-2 in advanced carcinomas of the head and neck].

The objective of this trial was to analyse the predictive character of the angiogenic factors vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and matrix metalloproteinase-2 (MMP-2) in the sera of patients with advanced carcinomas of the head and neck treated by primary radiochemotherapy. From 1992 to 1995, 25 patients with UICC stage cancers and one patient with stage III disease were treated in the departments of otolaryngology and radio-oncology of the University of Heidelberg according to a protocol of accelerated concomitant boost radiochemotherapy with carboplatin. The serum levels of VEGF, bFGF and MMP-2 were measured by enzyme-linked radiosorbent assay and data were correlated with followup findings (median time of follow up: 60 months). Patients with serum levels above normal were detected for VEGF in 4 patients, MMP-2 in 7 patients and for bFGF in 13 patients. An increase in bFGF serum levels above the upper limit of normal controls was significantly associated with a shorter time of locoregional control (P=0.036). In a covariate analysis bFGF proved to be independent of other prognostic factors, such as age, site, total tumor volume and response to therapy. No prognostic relevance of VEGF and MMP2 serum levels could be determined. The present suggest that bFGF is an independent prognostic factor for tumor control in advanced head and neck cancer after primary radiochemotherapy.

Adult↗
PubMed1999

[Construction workers as an extreme risk group for head and neck cancer?].

BACKGROUND: Workers in the construction industry carry an increased risk for head and neck cancer due to the high consumption of alcohol and tobacco plus exposure to occupational carcinogenic or co-carcinogenic agents. These latter substances include asbestos, tar products, metal dust, wood dust, cement dust and paints. RESULTS: The Heidelberg case-control studies showed a statistically increased risk of pharyngeal cancer (RR=2.5 adjusted for tobacco and alcohol) and laryngeal cancer (RR=2.3 adjusted for tobacco and alcohol) in the construction workers (23.3%) when compared to controls (8.2%). A random sample analysis of patients with head and neck cancer referred by the largest health assurance company in Heidelberg (AOK), revealed that 21.2% were employed in the construction industry. Similar results have been obtained in a number of international epidemiological studies. CONCLUSIONS: Our findings show that male construction workers who regularly consume alcohol and tobacco represent an extreme risk group for head and neck cancer. Measures for early detection are important and must be implemented carefully.

Adult↗
PubMed1999

[Prognostic significance of cell-cycle regulatory proteins for outcome after primary radiochemotherapy in patients with advanced head and neck cancer].

BACKGROUND: Primary radiochemotherapy is gaining increasing importance for the treatment of advanced head and neck squamous cell carcinomas. However, there is a lack of clinical factors concerning prognostic information in relation to treatment. In this pilot study, we examined whether molecular factors can provide such information. PATIENTS AND METHODS: The expression patterns and their possible prognostic relevance of the cell cycle regulatory proteins p53, p21(WAF/CIP1), Rb, p16(INK4A), CDK4 and Cyclin D1, MIB1 (Ki-67) and BCL-2 were analysed in pretreatment tumor biopsies from 43 patients with advanced carcinomas of the oropharynx (n = 26), hypopharynx (n = 10) and larynx (n = 7) by applying immunohistochemistry to paraffin sections of tumor specimens. All patients were treated by the same method of an accelerated "concomitant boost" radiochemotherapy with carboplatin in a phase II study. Median followup time was 56 months. RESULTS: No correlation was found between any of the markers and the remission rate, T-stage, N-stage, rate of loco-regional recurrences and distant metastases. However, independent of the tumor stage, patients with CDK4/cyclin-D1 overexpressing tumors had a significantly shortened overall survival (P = 0.014 and 0.026, respectively). CONCLUSION: The results of this pilot study indicate that CDK4 and cyclin D1 over-expression provide useful prognostic information about clinical outcome after primary radiochemotherapy of head and neck cancer patients.

Adult↗
PubMed1999

[The role of oncogenic human papillomaviruses in tonsillar squamous cell carcinomas with functional inactivation of the retinoblastoma protein].

In order to identify squamous cell carcinomas of the head and neck (HNSCC) with common biological and clinical features, we investigated the incidence and properties of carcinomas lacking retinoblastoma protein (pR6) cell cycle control. Of 208 HNSCC investigated, 23 (11%) showed a lack of pRb expression. The majority of these tumors (65%) were tonsillar carcinomas. The pRb-negative tonsillar tumors were all stage IV, had metastasized to lymph nodes at the time of diagnosis and were in general poorly differentiated or undifferentiated. Very significantly, the pRb-negative phenotype was strongly associated with the presence of oncogenic human papilloma viruses, implying a viral etiology and functional inactivation of pRb by the viral E7 oncoprotein. Despite the very adverse histopathological factors, patients with pRb-negative tonsillar carcinomas had a better clinical outcome, which was consistent with a uniform favorable responsiveness of these tumors to postoperative radiation therapy.

Carcinoma, Squamous Cell↗
PubMed1999

[Effect of primary radiochemotherapy on cellular and subcellular immunologic parameters].

PURPOSE: It is well known that chemotherapy and radiotherapy in other tumor sites than head and neck cause immunomodulating effects. The purpose of this trial was to assess the influence of radiochemotherapy in head and neck on cellular and subcellular immunity. PATIENTS AND METHODS: In a phase II/III-trial fifty patients with advanced squamous cell carcinoma of the head and neck were treated by simultaneously accelerated radiochemotherapy with Carboplatin (70 mg/sqm). Total radiation dose was 66 Gy/35 days. The following immunological parameters were investigated at several time points during therapy: total lymphocytes, total T-lymphocytes, CD4+ lymphocytes, CD8+ lymphocytes, monocytes, natural killer cells, interleukin-2-receptor-positive T-cells, MHC class II-positive B-cells, monocytes and T-cells, CD4/CD8-ratio; Cytokines: II-1, soluble II-1-receptor antagonist, II-2, soluble II-2-receptor, II-3, II-4, II-6, soluble II-6-receptor, II-8, interferon-alpha, granulocytes-macrophages-colony-stimulating-factor, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1. In addition, responses to the in vitro stimulation of lymphocytes by mitogens was tested. RESULTS: During therapy lymphocyte subpopulation counts decreased significantly but reversibly. Simultaneously, the function of lymphocytes was significantly but reversibly reduced. Also, II-8-concentration decreased significantly whereas concentrations of II-6 and soluble II-1-receptor antagonist significantly increased. CONCLUSIONS: The accelerated radiochemotherapy with Carboplatin induces a severe impairment of cellular immunity, followed by compensatory cytokine reaction.

Adult↗
PubMed1999

[Immunosuppression caused by head and neck surgery].

The immunomodulating effect of primary surgical intervention was investigated in 33 patients with squamous cell carcinomas of the oral cavity, pharynx and larynx. An operation time longer than 7 h was significantly associated with a decrease in lymphocytes, CD4(+) T-lymphocytes and CD8(+) T-lymphocytes. The CD4/CD8-ratio as a marker for the down-regulation of the cellular immune response was slightly decreased but was still in the normal range. CD4-lymphocyte counts increased 7 days after operation while CD8 lymphocytes were found elevated 4 weeks after surgery. The in vitro stimulation of the lymphocytes was impaired for 1 to 4 weeks. Interleukins, interferon-gamma and tumor necrosis factor did not show any changes after surgery. Decreases of lymphocytes, especially CD4(+) and CD8(+) lymphocytes, were significantly associated with the time of operation and the volume of blood loss. Extensive trauma, age, different kinds of anesthesia and intensive care interventions were not associated with specific immunomodulating effects, although these factors might be responsible for suppressing cytokine responses.

Adult↗
PubMed1999

Prognostic impact of total tumor volume and hemoglobin concentration on the outcome of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

PURPOSE: To identify prognostic clinical and treatment related factors for local control, distant metastasis-free survival, and survival by means of a multivariate analysis in patients with advanced squamous cell carcinoma of the head and neck after concomitant boost radiochemotherapy. PATIENTS AND METHODS: From 1992 to 1995, 68 patients with squamous cell cancer of the head and neck (93% stage IV disease) were treated with a simultaneous radiochemotherapy with Carboplatin using a concomitant boost technique. The total tumor volume (TTV) was quantitatively determined based on computed tomography scans in 56 patients. A Cox proportional hazards regression analysis was performed for each of the above endpoints and statistical significance of the Cox models was verified using the likelihood ratio test and Bonferroni correction for multiple testing. RESULTS: The survival and locoregional control rates at three years were 35 and 32%. The multivariate analysis revealed a significant association between the TTV and survival (P = 0.0008) and between the pretreatment serum hemoglobin concentration and locoregional control (P = 0.01) and survival (P = 0.05). The locoregional control was significantly associated with the N-stage (P = 0.007) and there was a good correlation between the N-stage and TTV in this study population. CONCLUSION: Our data corroborate the prognostic relevance of the tumor volume and hemoglobin concentration. In studies comparing the survival of patients with advanced cancer of the head and neck, the use of the TTV as a covariable may improve the statistical power.

Adult↗
PubMed1999

Acute and late toxicity, tumour control and intrinsic radiosensitivity of primary fibroblasts in vitro of patients with advanced head and neck cancer after concomitant boost radiochemotherapy.

BACKGROUND AND PURPOSE: The existence of hereditary factors influencing the cellular response to ionising radiation has led to the hypothesis that the inter-patient variability of clinical radiation reactions may, at least in part, be attributable to an individual, or intrinsic, radiosensitivity. Considerable effort has been spent in the development of test systems that would determine individual radiosensitivity before or early during radiotherapy to possibly predict treatment outcome, but the results are still conflicting. The present explorative study was therefore aimed at the detection of associations between acute and late radiation effects, tumour control and in vitro radiosensitivity of primary normal tissue fibroblasts. PATIENTS AND METHODS: Sixty-eight patients with squamous cell carcinoma of the head and neck (93% UICC stage IV) were treated with a simultaneous concomitant boost radiochemotherapy with Carboplatin as part of a prospective non-randomised multicenter study at the University of Heidelberg. Primary fibroblasts were obtained from skin biopsies prior to treatment from 25 unselected patients of this study and the SF2 was determined using the colony forming assay and high dose-rate irradiation. The median follow-up was 21 months (range 2.5-81 months). RESULTS: The locoregional control rate at three years was 32%. No significant association between acute (mucosa reaction grade 1 or 2 vs. grade 3 and 4), late radiation effects (subcutaneous fibrosis, osteonecrosis, larynx oedema), locoregional tumour control and SF2 of primary fibroblasts was found using Cox proportional hazards regression analysis, log-rank test and Mann-Whitney U-test. Although a steep dose-response relationship was observed for the radiation-induced severe larynx oedema, Cox proportional hazards regression analysis could not fully explain the occurrence of severe radiation-induced larynx oedema with the dose to the larynx (P = 0.09). In the subgroup of twenty-five patients, where the SF2 was determined, bivariate analysis revealed about the same non-significant influence of the dose to the larynx on the larynx oedema (P = 0.1) and no influence of the SF2 (P = 0.5). CONCLUSIONS: In our study of patients with advanced cancer of the head and neck, neither the normal fibroblast SF2 nor the severity of acute radiation effects were able to predict late radiation effects or locoregional tumour control.

Adult↗