Search PubMed⌕ Search

Biomedical subjects

A Dietz

Publications and source records attributed to A Dietz.

At least 91 records · Page 5Linked to original sources
PubMed1999

Rise of oxygenation in cervical lymph node metastasis during the initial course of radiochemotherapy.

It has been hypothesized that during radiation treatment a reoxygenation of hypoxic tumor tissue takes place. To test this hypothesis, we have investigated whether reoxygenation in lymph node metastases could be determined by invasive PO (2) measurements. Through a hypodermic needle inserted transcutaneously into tumor-positive lymph nodes, polarographic oxygen determinations were made in 18 patients with advanced squamous cell carcinomas of the oropharynx and hypopharynx. These measurements were performed before therapy and a week after the onset of radiotherapy or radiochemotherapy, respectively. Low PO (2) values before treatment (mean value of the patient's median was 12.6 mm Hg PO (2)) and a mean hypoxic fraction (PO (2) < 5 mm Hg) of 39.6% indicated manifest tumor hypoxia. After 1 week of treatment, a significant increase in the median PO (2) (mean value of shift: 7.3 mm Hg) and a reduction in the hypoxic fraction (mean value of shift: 13.4% PO (2) < 5 mm Hg, P < 0.03) were observed after both radiotherapy and radiochemotherapy. Thus invasive PO (2) histography fulfills the requirements for a method to confirm tumor hypoxia in head and neck tumors. The results obtained indicate that reoxygenation occurs during the initial phases of radiotherapy and radiochemotherapy, and they will form the basis for future comparative investigations on the possible influence of hypoxic parameters on tumor responsiveness toward radiation and radiochemotherapy.

Adult↗
PubMed1998

TP53 DNA contact mutations are selectively associated with allelic loss and have a strong clinical impact in head and neck cancer.

Recent studies have suggested that different mutation types within the core domain of the tumour suppressor protein p53, i.e. DNA contact mutations and structural mutations, confer different biological properties. We have analysed in 86 head and neck squamous cell carcinomas (HNSCC), whether these p53 mutation types have a differential clinical impact. Thirty-seven missense mutations were identified. Thirteen of these (36%) were DNA contact mutations, occurring in the L3 loop, in the H2 loop sheet helix motif, in the S10 beta strand and in Zinc binding residues. Microsatellite marker analysis revealed a selective association between these mutations and the loss of wild-type alleles (100% LOH vs 50% LOH in tumours with structural mutations; P=0.0034, Fisher's exact, 2-tailed). In comparison to structural mutations or to the absence of mutations in the core domain, DNA contact mutations were associated with higher tumour stages (84.6% vs 62%), a higher incidence of lymph node metastasis (91.7% vs 56%; P=0.014, Fisher's exact, 2-tailed), a shortened recurrence-free survival (8.1 months vs 23.7 months, P=0.047, log rank test) and overall survival (11 months vs 29.2 months; P=0.003, log rank test). The latter was also the case when only stage IV tumours were analysed (P=0.0055, log rank test). These data indicate that in HNSCC, TP53 DNA contact mutations confer a strong selection pressure to eliminate wild-type alleles, and that they result in an accelerated tumour progression and reduced therapeutic responsiveness.

Adult↗
PubMed1998

Etiological involvement of oncogenic human papillomavirus in tonsillar squamous cell carcinomas lacking retinoblastoma cell cycle control.

Two hundred eight primary squamous cell carcinomas of the head and neck have been analyzed with respect to the presence of the retinoblastoma tumor suppressor protein, pRb. Of these, 23 tumors (11%) that preferentially localized to the tonsils revealed complete absence or dramatic reduction in the amount of pRb. Other cell cycle components, cyclin D1 and p16INK4A, which are intimately related to pRb through an autoregulatory loop, were also dramatically decreased or overexpressed, respectively, in these pRb-defective tumors. On the other hand, the majority of the pRb-defective tumors contained the wild-type p53 gene. No evidence was found for genetic defects at the Rb locus in these tumors. Very significantly, in 11 of 12 pRb-defective tonsillar tumors, but in none of 9 pRb-positive tonsillar tumors (P < 10[-7]), DNA of oncogenic human papillomavirus types was identified, providing a strong indication for a human papillomavirus-associated etiology of these tumors and suggesting the functional inactivation of the pRb protein by the viral E7 gene product. In comparison to all head and neck squamous cell carcinomas studied, the pRb-defective tonsillar tumors were in general more poorly differentiated (P = 0.0059), and they were all metastatic at the time of resection. Of particular clinical interest, despite these adverse histopathological factors, the clinical outcome for these patients was relatively favorable, strongly implying that the pRb-defective tumors responded uniformly well toward postoperative radiation therapy.

Carcinoma, Squamous Cell↗
PubMed1998

[Chronic laryngeal edema as a late reaction to radiochemotherapy].

In addition to mucositis and myelotoxicity as well known early reactions after radiotherapy or radiochemotherapy in advanced head and neck tumors, late toxicity following treatment is an often underestimated problem. Between 1992 and 1995, 68 patients with advanced oro- and hypopharyngeal tumors were treated primarily with accelerated concomitant boost radiochemotherapy (total dose irradiations of 66 Gy and carboplatin as chemotherapy). Ninety-three per cent of the patients had stage IV disease according to the UICC-TNM classification. Monitoring of follow-up included late toxicity with special attention given to laryngeal edema. In 37 patients (54%) edema of the larynx as a late complication of radiochemotherapy was observed by clinical investigation and CT scan. The median onset of laryngeal edema was found 121 days after completion of therapy, with a median time of observation of 250 days. Observations in these patients demonstrated the chronic character of this edema. An increase in the laryngeal edema in 5 cases resulted in tracheostomy. Laryngeal edema in 10 patients was associated with recurrence of tumor. These results show that after xerostomia laryngeal edema is the main late toxicity in the head and neck after radiochemotherapy and should lead to further investigations to exclude possible recurrent tumor.

Adult↗
PubMed1998

[Macrolide antibiotic-induced vasculitis (Churg-Strauss syndrome)].

BACKGROUND: Macrolides are known to have relatively few side effects and are prescribed in cases of allergic reaction to penicillin. The new macrolides, for example Azithromycin and Roxithromycin, are increasingly preferred over erythromycin at the ear, nose, and throat out-patient department due to improved oral reabsorption (acid resistance), better penetration into tissue, prolonged half-life, extended antibacterial activity, modest side effects, and better pharmacokinetics. There are only few case reports concerning side effects of macrolides. We report on the appearance of a Churg Strauss-Syndrome (CSS) in a patient following intake of the macrolide antibiotic azithromycin and roxithromycin. PATIENT: A 50-year-old patient with asthma for three years presented with arthritis and mononeuritis multiplex. Laboratory and radiological investigations revealed eosinophilia (64%), eosinophilic infiltrations of bone marrow, raised IgE-level, and transient pulmonary infiltrates. THERAPY AND DEVELOPMENT: Intravenous steroid therapy was started and resulted in normalization of eosinophilia, IgE-level, and asthmatic symptoms. The neurologic deficits showed only a weak tendency for improvement. CONCLUSION: The diagnosis of CSS was established on the basis of clinical criterias and laboratory investigations. The diagnosis was supported by the fact that a similar course of the disease was observed one year ago following administration of azithromycin, another macrolide.

Anti-Bacterial Agents↗
PubMed1997

[Drug therapy of cardiac arrhythmias 199].

Current antiarrhythmic drug therapy is employed in strict compliance with the proper indication, which is itself limited by the side effects of the available drugs, and modified by the increasing success of such non-drug options as electrical ablation and implantable cardioverters/defibrillators. Drug treatment is restricted to 3 major indications, regular paroxysmal supraventricular tachycardias, atrial flutter and fibrillation, and ventricular tachycardias. Class IA and IC agents are used only to treat supraventricular and ventricular arrhythmias with no structural heart disease. Class III drugs, e.g. sotalol and in particular amiodarone are used preferentially to treat the pre-damaged heart, in particular left-ventricular functional impairment and in coronary heart disease in consideration of their side effects. In the case of the most common treatment-requiring arrhythmia-atrial fibrillation-anticoagulation alone may be indicated. For the prevention of sudden death, beta-blockers continue to be the drugs of first choice.

Anti-Arrhythmia Agents↗
PubMed1997

Predictive value of the flow cytometric PCNA assay (proliferating cell nuclear antigen) in head and neck tumors after accelerated-hyperfractionated radiochemotherapy.

PURPOSE: Proliferation of tumor cells during radiotherapy may limit tumor control, especially in rapidly proliferating tumors such as head and neck carcinomas. We present a flow cytometric method for detection of PCNA in solid head and neck tumors and how these data correlate with outcome. METHODS AND MATERIALS: Pretherapeutic biopsies of 20 inoperable patients with Stage IV squamous cell carcinoma were examined. Biparametric flow cytometry was done after anti-PCNA (PC10) and propidium iodine staining were performed. PCNA index (percentage PCNA positive cells), DNA index, and S phase fraction (SPF, euploid tumors only) were determined. The therapy consisted of an accelerated-hyperfractionated radiochemotherapy (66 Gy/5 weeks, concomitant boost of 1.6 Gy/day in weeks 4+5, Carboplatin 5 x 70 mg/m2 in weeks 1+5). The median follow-up time was 30 months. RESULTS: Fourteen patients suffered from disease progession and 12 died. Median actuarial, cause-specific survival, and disease-free survival (DFS) times were 17 and 9 months, respectively. PCNA indices ranged from 4 to 70% (median 9%); there were 7 aneuploid and 13 euploid tumors. SPF ranged from 4 to 14.5% (median 10.5%). Neither SPF nor ploidy had a significant influence on outcome. Patients were divided according to PCNA index in higher (n = 10) and lower (n = 10) than the median. Survival and DFS were 13 and 6 months for the group >9% and 20 and 15 months for the group <9%. The difference in DFS was significant (p = 0.03, log rank test). CONCLUSION: These results fall in line with other studies showing the influence of pretherapeutic proliferation on outcome after radiotherapy. Although the moderately accelerated therapy regimen certainly reduces the influence of proliferation on outcome, patients with faster proliferating tumors still have a worse outcome. DFS is the more relevant endpoint in this study because of effective salvage therapies, which influence survival.

Adult↗
PubMed1997

[Polarographic detection of reoxygenation of lymph node metastases in the initial phase of primary radio- and radiochemotherapy in patients with advanced squamous epithelial carcinomas of the head and neck].

The therapeutic effect of radiotherapy depends amongst other things on the degree of oxygenation of tumour tissue. Epithelial carcinomas of the head-neck region exhibit considerable hypoxic areas which vary markedly between individuals and not encompassed by current staging and grading. It is assumed that during radiation treatment a reoxygenation of hypoxic tumour cells takes place. It was investigated wether the occurrence of reoxygenation could be determined by invasive oxygen partial pressure measurements in lymph node metastases. Using a needle probe inserted transcutaneously into a lymph node polarographic oxygen determinations (Eppendorf pO2-Histiograph) were made on 13 patients with advanced oro- and hypopharyngeal carcinomas before therapy and after a week of accelerated radio- or radiochemotherapy. Low pO2 values before treatment (median 13.5 mmHg, average 20.3 mmHg) and a hypoxic fraction (pO2 < 10 mmHg) of 45.2% indicated manifest tumour hypoxia. After the first week of treatment a significant increase in the median- (24.1 mmHg) and the average pO2 (28.2 mmHg) as well as a reduction in the hypoxic fraction (27%) were observed. Invasive pO2 histiography fulfils the requirements for a method to confirm tumour hypoxia in head-neck tumours. The results obtained indicate that reoxygenation occurs during the initial phases of radio- and radio-chemotherapy.

Adult↗
PubMed1997

[Occupational exposure to paint, lacquer and solvents, and cancer risk in the area of the upper aero-digestive tract].

So far, only few studies exist that have investigated the influence of occupational exposure to paint and lacquer on the risk of cancer in the upper aerodigestive tract. Based on data from the Heidelberg case control study which enrolled 369 patients with carcinomas of the upper aerodigestive tract and 1476 randomized control subjects, the relative risk of head and neck cancer in patients exposed to paint, lacquer and varnish was analyzed. The relative risk (RR) of squamous cell cancer (after adjustment for possible alcohol and tobacco effects) was significantly increased for the larynx (RR = 2.3) and the oral cavity (RR = 3.6). However, this risk was not increased for the pharynx. Our findings and a critical analysis of the literature provide evidence that chronic exposure to paint, varnish and lacquer is a definite risk factor for cancer of the upper aerodigestive tract. Further studies are required to confirm these findings, and to identify more precisely toxic substances encountered in the workplace.

Carcinoma, Squamous Cell↗
PubMed1997

In vitro radiosensitivity of primary human fibroblasts. Lack of correlation with acute radiation toxicity in patients with head and neck cancer.

BACKGROUND AND PURPOSE: There is a considerable hope among clinicians and radiobiologists to detect genetically radiosensitive patients prior to radiotherapy. A predictive assay would enable adjustment of the total irradiation dose to the individual at a constant risk of normal tissue complications. In this prospective study, the clonogenic survival assay for primary human fibroblasts to determine radiosensitivity in vitro was evaluated and then correlated with clinically observed acute radiation reactions. MATERIALS AND METHODS: One hundred twenty-five independent survival experiments with primary fibroblasts derived from 63 biopsies from 55 cancer and non-cancer patients were performed. RESULTS: A wide variation of cell survival between biopsies was detected. Statistical analysis revealed a highly significantly larger interindividual than intraindividual variation of SF2 values. However, a considerable scatter of SF2 values in repeated experiments was observed in individual cases. Age, gender, disease status (cancer patient, non-cancer patient) and origin of fibroblasts (skin, periodontal tissue) were demonstrated not to be statistically significant confounding factors on the intrinsic radiosensitivity in vitro. In a prospective study, no correlation of the SF2 and acute reactions in 25 patients with head and neck cancer treated with a primary accelerated radiochemotherapy was detected. CONCLUSION: Our data show that the clonogenic assay is able to distinguish between intrinsic radiosensitivities of primary human fibroblasts if a statistical approach is used but does not predict acute radiation toxicity.

Acute Disease↗
PubMed1997

Prognostic significance of color Doppler findings in head and neck tumors.

We examined whether or not the degree of tumor vascularity in lymph node metastases as depicted by color Doppler is associated with a patient's prognosis. Cervical lymph node metastases in 25 patients with head and neck cancer were examined before combined accelerated radiotherapy and chemotherapy. The findings were quantified using a computer-assisted protocol that quantitatively describes color Doppler images by the relative color pixel density (CPD) and the color hues, which are numerically expressed by the mean color value (MCV). We found that, in the patient group with a CPD below median, the median survival was 958 days and, in the group with a higher CPD, it was 423 days (p = 0.05). The time to detection of distant metastases was 18 months with a low CPD, and 6 months with a high CPD (p = 0.05). However, the time to local or nodal progression was not different between the groups. The MCV was not correlated with prognostic data. These results indicate that, in patients with metastatic head and neck cancer, highly vascularized lymph nodes detected with color Doppler sonography may indicate a shorter survival and earlier occurrence of distant metastases.

Blood Flow Velocity↗
PubMed1996

[Ultrasound diagnosis in primary staging of head-neck tumors].

The radiologic imaging methods play an important role in the precise staging as basic requirement for an effective concept of tumor therapy. The accuracy of ultrasound in the primary staging according to the TNM-classification (UICC) was therefore prospectively investigated in 260 patients with head and neck tumors of the clinical stages T1N0 to T4N3. The clinically (C1) and sonographically (C2) evaluated pretherapeutic stages were compared to the postoperative histopathologic tumor classifications. The clinical staging was correct in 75.0%, high in 7.7%, low in 17.3%, the N-stages were correct in 59.2%, high in 17.7%, low in 23.1%. The sonographic staging was apparently superior with the T-classifications correct in 92.3%, high in 7.7%, low 0.0%. The N-stages were correct in 89.6%, high in 9.2%, low in 1.2%. The accuracy of combined TN classification rose from clinical 46.5% to 84.6% by sonography. Accompanying inflammations, foregoing biopsies and tooth extractions were the main reasons for incorrect staging. Therefore, the thorough sonographic investigation performed after the clinical examination and before invasive procedures, due to little patient discomfort, good availability and high accuracy, is an excellent sectional imaging method for staging, therapy-planning and follow up of tumors of the head and neck especially of the orofacial regions.

Adult↗
PubMed1996

[Accelerated hyperfractionated simultaneous radiochemotherapy in advanced head-neck carcinomas in comparison: split course and concomitant boost concept].

PATIENTS: Between 1989 and 1992, 38 patients with advanced squamous cell carcinomas of the head and neck were treated by an accelerated hyperfractionated split-course radiochemotherapy (SCRC). This therapy was carried out at the ENT department and department of radiooncology of the University of Heidelberg. Within 51 days, 70.2 Gy were applied in three courses. In every course, simultaneous chemotherapy with cisplatin (60 mg/m2/week)/5 Fu (bolus: 350 mg/m2/d)/Leucovorin (bolus: 50 mg/m2 + 100 mg/m2/24 h) was carried out. Between 1992 and 1994, 50 patients suffering from advanced head and neck cancer (stage III, V) were also treated with an accelerated hyperfractionated concomitant-boost radiochemotherapy (CBRC) at the same departments. A total dose of 66 Gy, was applied within 33 days. The patients were also treated with simultaneous chemotherapy with carboplatin (70 mg/m2/24 h) in the first and fifth week. RESULTS: In about 50% of the patients treated with SCRC, the therapy was more than 10 days longer than the scheduled period. The lack of compliance due to toxicity was considered as one of the main reasons for this delay. After the first course of SCRC, eight of 38 patients showed mucositis of the upper aerodigestive tract (WHO grade > 3); after the second course, 11 of 38 patients; and after the third course, 15 of 38 patients. Fifty-two percent of the patients developed emesis, 10% leucopenia < 1 nl, 10% nephrotoxicity, 3% pancreatitis, 3% thrombosis, 3% gastritis, and 3% auditory threshold shifts of about more than 10 dB. In about 7.5% of the patients treated with CBRC, the therapy was more than 10 days longer than the scheduled period. The mucositis of the upper aerodigestive tract (50% of the patients showed WHO-grade > 3) was considered to be the main reason for this. In four patients a neutropenia < 1 nl was detected, in one patient anemia < 7 g/dl and n 33 patients thrombocytopenia < 100/nl. CONCLUSIONS: In conclusion, the concomitant boost radiochemotherapy showed a lower toxicity and higher acceptance than the split-course radiochemotherapy. This is documented in lower protocol delays and better results in the two-years survival time in case of concomitant boost radiotherapy.

Adult↗
PubMed1996

Phase I clinical and pharmacokinetic study of irinotecan, fluorouracil, and leucovorin in patients with advanced solid tumors.

PURPOSE: To determine the maximum-tolerable dose (MTD) of fluorouracil (5FU) when given with fixed doses of leucovorin and irinotecan (CPT-11), to define the dose-limiting toxicities of this combination, and to evaluate the effect of 5FU on the pharmacokinetics of CPT-11. PATIENTS AND METHODS: CPT-11, leucovorin, and 5FU were administered in repeated 6-week cycles that consisted of weekly treatment with all three drugs for 4 consecutive weeks followed by a 2-week break. On day 1 of treatment, CPT-11 alone was given by 90-minute infusion, and pharmacokinetic sampling was performed over 24 hours. Leucovorin and 5FU were administered by brief intravenous injection on day 2. On days 8, 15, and 22, CPT-11 infusion was immediately followed by leucovorin and then 5FU. A second 24-hour pharmacokinetic sampling was performed on day 8, which permitted comparison of the pharmacokinetics of CPT-11 with and without 5FU. For the second 6-week cycle, leucovorin was administered first, followed by 5FU and then CPT-11, and a third pharmacokinetic sampling was performed. RESULTS: Forty-two patients were entered onto this trial. The CPT-11 dose was initially fixed at 100 mg/m2. Leucovorin was fixed at 20 mg/m2. 5FU doses of 210, 265, 340, 425, and 500 mg/m2 were studied. When the 500-mg/m2 dose of 5FU was found to be tolerable, this was then maintained and CPT-11 was escalated to 125 and then 150 mg/m2. This final CPT-11 dose exceeded the MTD. Neutropenia was the major dose-limiting toxicity. Diarrhea was common, but was rarely dose-limiting. Coadministration of 5FU had no substantial effect on the pharmacokinetics of CPT-11 or SN-38. Among the 38 patients with colorectal cancer, six partial responses (PRs) were seen in this predominantly 5FU-refractory patient population. CONCLUSION: 5FU does not substantially affect the metabolism of CPT-11 to its active metabolite, SN-38. The combination of CPT-11125 mg/m2, 5FU 500 mg/m2, and leucovorin 20 mg/m2 is feasible and tolerable on this schedule.

Adult↗
PubMed1996

[Distant metastasis and incidence of second carcinomas in patients with oropharyngeal and hypopharyngeal carcinomas].

Thirteen per cent of oropharyngeal carcinoma patients (n = 23/178) developed a secondary carcinoma, and 10% of hypopharyngeal carcinoma patients (n = 11/113). The latency time of occurrence of the second carcinoma was 37 months for the oropharyngeal tumors and 25 months for the hypopharyngeal tumors. The main location of the secondary cancers was the oral cavity and oropharynx. Early recognition of secondary cancers by routine follow-up examinations made surgical removal possible in most of the patients. The post-operative survival time for the oropharyngeal lesions was 59 months and was 34 months for the hypopharyngeal cancers. Distant metastases were found in 13% of the patients with oropharyngeal cancers and in 17% with hypopharyngeal cancer and were mainly located in the lungs. After diagnosis of distant metastases patients with oropharyngeal lesions died within 4.5 months and those with hypopharyngeal tumors died within 9 months.

Adult↗