Biomedical subjects

R Willers

Publications and source records attributed to R Willers.

76 records · Page 5Linked to original sources

PubMedDate not supplied

An approach for cure: PEI-chemotherapy and regional deep hyperthermia in children and adolescents with unresectable malignant tumors.

BACKGROUND: Elevated temperatures of 40 - 44 degrees C increase the actions of various anticancer drugs including N-lost derivatives, cytotoxic antibiotics and platinum analoga. In clinical usage thermochemotherapy (TCH) should facilitate surgical resection and ameliorate local tumor control. PATIENTS AND METHODS: From 07/1993 to 12/2002 a total of 39 patients have been enrolled onto a phase-II study (female = 24, male = 15, age 1 - 37.5 years, median 5.2). Among these, 24 patients had extracranial non-testicular germ cell tumors and 15 patients soft tissue or chondrosarcomas. INDICATION: locoregional relapse (n = 29) or unresectable tumor after neoadjuvant chemotherapy (n = 10). Among these two groups, there were ten patients with poor response or progressive disease under primary or relapse chemotherapy. Ten out of the 29 relapse patients had more than one relapse. Tumor site: pelvis (30), abdomen (4), head and neck (2), proximal leg (2) and lumbar spine (1). Thermochemotherapy (TCH): 1800 - 2000 mg ifosfamide/m (2) and 100 mg etoposide/m (2) on days 1 - 4 and 40 mg cisplatin/m (2) on days 1 + 4 combined with regional deep hyperthermia (42 - 44 degrees C, 1 h) on days 1 + 4. RESULTS: In 39 protocol patients a total of 166 TCH courses (332 heat sessions) were applied. 20 patients achieved complete response, and 10 patients achieved partial response. TCH was followed by surgical tumor resection in 28/39 patients and/or radiotherapy in 13/39 patients. At a median follow-up of 27 months, outcome in this high-risk patient population was 22 NED, 3 AWD, 12 DOD, 2 DOC. Five year event free (EFS) and overall survival (OS) for the whole study cohort was 0.39 +/- 0.11 (20/39 patients) and 0.52 +/- 0.11 (25/39 patients), respectively. CONCLUSION: TCH shows substantial therapeutic efficacy and facilitates complete tumor resection in 14 out of 28 operated patients. Multimodal treatment including TCH, surgical resection and/or radiotherapy leads to sustained remission in the majority of patients with locoregional tumor recurrence. The therapeutic effect is most pronounced, if TCH is administered at first relapse. Due to the clinical and histologic heterogeneity the number of patients eligible for TCH is limited. Therefore, a more valid assessment of treatment efficacy can only be made by a matched-pair comparison in cooperation with the clinical registers.

Abdominal Neoplasms↗

PubMedDate not supplied

The prognostic significance of proliferative activity, apoptosis and expression of DNA topoisomerase II alpha in multimodally-treated oesophageal squamous cell carcinoma.

The present study retrospectively examined the correlation between the outcome of patients with locally advanced oesophageal squamous cell carcinoma (cT3-4 cN0-1 cM0) after multimodal treatment (radiochemotherapy +/- surgical resection) and the parameters proliferative activity, apoptotic index and expression of the nuclear enzyme topoisomerase II alpha (topo II alpha) in pre-therapeutic tumour biopsies. Fifty-eight patients who took part in a prospective multicentred trial received radiochemotherapy, optionally followed by surgery. Pre-therapeutic biopsies were immunohistochemically investigated for the extent of proliferation (MIB-I index) and expression of the topo II alpha-enzyme. The apoptotic index was determined by the TUNEL-assay. The three parameters were correlated with tumour response to polychemotherapy and with overall survival. Topo II alpha expression was found in all samples with different percentages of positive cells. The proliferation indices ranged between 9% and 97% (median: 43%) while the apoptotic indices ranged between 0.2% and 2.8% (median: 0.5%). Strong expression of topo II alpha (>50% positive tumour cells) was positively-correlated with response to polychemotherapy (p=0.016) whereas proliferative activity or apoptotic index showed no impact. None of the three parameters under investigation was predictive of overall survival. Pre-therapeutic determination of topo II alpha expression may predict chemosensitivity of oesophageal squamous cell carcinomas. However, determination of proliferative activity and apoptotic index has no predictive value.

Antigens, Neoplasm↗

PubMedDate not supplied

Tumor vascularization and prognosis in squamous cell carcinomas of the esophagus.

Quantification of tumor vascularization has recently been shown to be a parameter of potential prognostic significance in various types of malignant tumors. To determine the prognostic value of tumor vascularization in esophageal cancer, tumor samples from 150 patients with squamous cell carcinoma of the esophagus and 10 samples of normal esophageal mucosa were stained immunohistochemically with the monoclonal antibody QBEND/10 (CD34), which recognises endothelial cells. Using light microscopy, the number of microvessels was counted in the areas with the highest microvessel density (MVD). The microvessel density was significantly higher in the normal esophageal mucosa (mean: 130/mm2) than in the tumor samples (mean: 69/mm2, p = 0.0001). Correlation of the MVD in the tumor tissue with other prognostic factors showed significantly lower microvessel counts in tumors with lymphatic-vessel invasion (p = 0.0076) and in high pT-stages (p = 0.0081). No significant correlation was found between the MVD and pN stage, tumor size, tumor grade, blood-vessel invasion and proliferative activity. In the univariate survival analysis no significant differences were found between poorly vascularized tumors and highly vascularized tumors. A Cox proportional hazard regression selected the parameters lymphatic-vessel invasion (p = 0.0001), pT stage (p = 0.0034) and pN stage (p = 0.0256) but not MVD as independent prognostic variables.

Age Factors↗

PubMedDate not supplied

The prognostic significance of epidermal growth factor receptor expression in squamous cell carcinomas of the oesophagus.

EGFR expression in 150 potentially curative resected squamous cell carcinomas of the oesophagus was analyzed immunohistochemically and correlated with survival. Altogether, 124 of 150 (82.7%) tumours expressed different levels of EGFR. The percentage of tumour cells expressing EGFR varied greatly between the different tumours (median: 70%). 62 (50.0%) tumours showed weak and intense staining, respectively. Regarding the staining pattern 19 (15.3%) tumours showed exclusively membraneous immunoreactivity, 27 (21.8%) an exclusively cytoplasmic immunoreactivity and 78 (62.9%) a mixed staining pattern. No significant correlation however could be found between EGFR expression and various clinicopathologic parameters such as pT category, pN category, tumour size, histologic grade and blood vessel invasion. In univariate survival analysis, no correlation between EGFR expression and postoperative survival time was observed. In a forward multivariate Cox regression analysis only the parameters lymphatic-vessel invasion (p = 0.001), pT category (p = 0.0034) and pN category (p = 0.0256), but not the EGFR expression, could be verified as independent prognostic variables. In conclusion, the evaluation of the EGFR expression does not provide prognostic information for patients who underwent potentially curative resection for SCC of the oesophagus.

Adult↗