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Biomedical subjects

C Lautenschläger

Publications and source records attributed to C Lautenschläger.

At least 19 recordsLinked to original sources

Expression of the stem cell self-renewal gene Hiwi and risk of tumour-related death in patients with soft-tissue sarcoma.

Self-renewal is considered as a common property of stem cells. Dysregulation of stem cell self-renewal is likely a requirement for the development of cancer. Hiwi, the human Piwi gene, encodes a protein responsible for stem cell self-renewal. In this study, we investigated the expression of Hiwi at the RNA level by real-time quantitative PCR in 65 primary soft-tissue sarcomas (STS) and ascertained its impact on prognosis for STS patients. In a multivariate Cox's proportional hazards regression model, we found that an increased expression of Hiwi mRNA is a significant negative prognostic factor for patients with STS (P=0.017; relative risk 4.6, 95% confidence interval (CI) 1.3-16.1) compared to medium expression of Hiwi transcript. However, a low expression of Hiwi transcript is correlated with a 2.4-fold (CI 0.7-8.0) increased risk, but this effect was not significant (P=0.17). Altogether, high-level expression of Hiwi mRNA identifies STS patients at high risk of tumour-related death. This is the first report showing a correlation between expression of a gene involved in stem cell self-renewal and prognosis of cancer patients.

Adult↗

[Cataract types in diabetics and non-diabetics: a densitometric study with the Topcon-Scheimpflug camera].

BACKGROUND: The purpose of this study was to compare types of cataract which appear in patients with the cataractogenous risk factor diabetes mellitus type II and in non-diabetics. MATERIALS AND METHODS: The opaque lenses of 46 diabetics (group I) and 83 non-diabetics (group II) in the age range of 55-93 years, who had to undergo a cataract operation, were documented using the Topcon-Scheimpflug camera SL-45 followed by densitometric analysis. RESULTS: Although there was no significant difference relating to the metabolic disorder, we found a higher percentage of opacity of the deeper anterior (I = 8.7 % II = 3.6 %) as well as in the anterior and posterior cortex (I = 13.0 % II = 8.4 %) comparing diabetics and non-diabetics. CONCLUSION: Diabetics revealed a higher percentage of opacity of the area of the cortex than non-diabetics without detecting any significance. Thereby, we could show positive associations between the existence of diabetes mellitus type II and a higher risk of opacities of the cortex.

Aged↗

[Origin of shoulder pain after "neck dissection". Importance of the cervical plexus].

BACKGROUND: The role of sensitive parts of the cervical plexus for the development of neuropathic pain is not yet clear. Our study investigated the correlation between shoulder pain and cervical plexus damage after different types of neck dissection (ND). MATERIAL AND METHODS: The sensitivity for warm/cold and sharp/blunt was tested in the dermatomes of C2, C3, C4, and the minor occipital nerve. Shoulder pain was measured semiquantitatively by a rating scale. RESULTS: Motion-dependent shoulder pain was observed 6 months postoperatively in 50% after resection and in 29.2% after preservation of these structures. Pain occurred more frequently following radical ND than after modified radical types 1 and 3 ND. DISCUSSION: Our investigations showed that the superficial cervical plexus function is assessable by cutaneous sensitivity tests. The minor occipital nerve seemed to be less affected. Fewer pain symptoms in cases with preserved cervical plexus could be demonstrated. We can conclude that preservation of the superficial cervical plexus is important to diminish postoperative shoulder pain.

Cervical Plexus↗

SCC antigen in the serum as an independent prognostic factor in operable squamous cell carcinoma of the cervix.

The aim of this study was to retrospectively examine whether the occurrence of squamous cell carcinoma (SCC) antigen tumour marker in the serum has prognostic significance in operable SCC of the cervix at the International Federation of Gynaecology and Obstetrics (FIGO) stages IA2-IIB. A total of 129 patients who had undergone a radical hysterectomy for SCC of the uterine cervix at the Department of Gynecology of the Martin-Luther University, Halle-Wittenberg in 1991-2000 were included. SCC antigen (Ag) was measured by IMx SCC-Ag microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, IL, USA). To assess the prognostic value of SCC antigen in the serum, we used a step-by-step multivariate analysis based on the Cox proportional hazard regression model. Using a cut-off value of 3.0 ng/ml, we detected preoperative SCC antigen in the serum as an independent prognostic factor in SCC of the cervix, both for recurrence-free and overall survival (P=0.003 and 0.0078). In this retrospective analysis the value of the SCC antigen tumour marker correlates with prognosis in operable SCC of the cervix, independent of tumour size, pelvic nodal status, cervical stroma infiltration, parametrial spread and tumour grading.

Adult↗

Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non-small cell lung cancer.

OBJECTIVES: This retrospective study evaluates the probability of survival in patients who had undergone resection for non-small cell lung cancer (NSCLC) and in whom residual disease at the resection margins was found. METHODS: During a period of 6 years, 596 patients with NSCLC were operated upon with curative intention. Residual disease at the resection margin was divided into microscopic (R1) and macroscopic (R2). RESULTS: Twenty-six patients (4.4%) showed R1 and 12 (2%) R2 residual disease. An extrabronchial (thoracic wall, vessels) R1 situation was found in five patients and a bronchial R1 infiltration in 21 cases. The bronchial resection margin was subject to peribronchial infiltration in most cases (16/21). A total of 17/21 (65%) patients with bronchial infiltration had N2 disease. Thirty day lethality was 3.8% in the R1 group. Fifteen patients had postoperative irradiation. The 5-year survival rate for patients with R1 resection was 14%. The differences in survival between patients with extrabronchial vs. bronchial infiltration and N0/N1 vs. N2 were significant using univariate analysis. Adjuvant radiation did not result (especially in N2 disease) in a survival benefit. Among 12 patients with macroscopic residual disease (R2), 3/12 (25%) died within the first 30 days after the operation, and none of the R2 patients survived the first year after the operation. CONCLUSIONS: Patients with an R1 situation have a survival rate of 14% comparable to curative resected patients (RO) in stage III. Adjuvant radiation had no clear effect on survival. Patients with macroscopic tumor (R2) should receive palliative treatment after the operation depending on their condition.

Adenocarcinoma↗

Increased survivin transcript levels: an independent negative predictor of survival in soft tissue sarcoma patients.

Survivin, a recently identified inhibitor of apoptosis protein (IAP), is expressed in diverse embryonic tissues and in various human cancers. We have investigated the quantitative expression of survivin mRNA by a sensitive TaqMan-based RT-PCR assay in tissue samples from 94 patients with soft tissue sarcomas (STS). Survivin transcript levels were measured and normalized to GAPDH transcripts. By using a multivariate Cox regression analysis, we found an inverse correlation between the level of survivin mRNA (ratio >2 zmol survivin/amol GAPDH) and the rate of overall survival (p = 0.009, RR = 2.7). Survivin transcript variants as detected by qualitative RT-PCR analysis were revealed in 36 of 56 STS patients (64%). Only survivin DeltaEx3 and/or full-length survivin variants but not survivin 2B were identified. Our results suggest that a higher level of survivin mRNA is an independent predictor of survival for STS patients.

Adolescent↗

Amplification of the MDM2 gene, but not expression of splice variants of MDM2 MRNA, is associated with prognosis in soft tissue sarcoma.

The MDM2 gene encodes a 90-kDa oncoprotein that is overexpressed in several human carcinomas, osteosarcomas, gliomas and soft tissue sarcomas (STSs). This overexpression is the result of several mechanisms, for example, enhanced transcription or translation, gene amplification and alternative splicing. We found that 19 of 67 (28.4%) STS specimens contained an amplified MDM2 gene. The amplification was more likely to be present in grade 1 tumors than in grade 2 or 3 tumors (58% of grade 1 tumors vs. 15% of grade 2 or 3 tumors, p = 0.001, chi(2) test). Furthermore, patients with tumors that contained an amplified MDM2 gene had a survival estimate (87 months) that was longer than that of patients with tumors that lacked an amplified gene (40 months; p = 0.02, log-rank test). Alternatively and aberrantly spliced MDM2 mRNAs were detected in human STSs by a highly sensitive reverse transcription-polymerase chain reaction method. Of 71 tumor samples, 38 (54%) showed evidence of the spliced forms, which included MDM2-A, MDM2-B and several variants exclusively expressed in STSs. A common feature of all forms was the absence of the MDM2 N-terminal region, which includes the TP53-binding region. Furthermore, the presence of the spliced forms was associated with elevated levels of TP53 (p = 0.01, chi(2) test). Although the presence of spliced forms was associated with late-stage tumor phenotypes (p = 0.05, chi(2) test), we observed no relationship between the presence of splice variants and patient outcome.

Alleles↗

Multivariate analysis of clinicopathologic parameters for the insular subtype of differentiated thyroid carcinoma.

HYPOTHESIS: Insular carcinoma represents a more aggressive subtype of differentiated thyroid cancer on multivariate analysis after controlling for various clinicopathologic parameters. DESIGN: Retrospective analysis. SETTING: Tertiary referral center at a university hospital. PATIENTS: One hundred twenty-seven consecutive patients having a histological diagnosis of the follicular variant of papillary thyroid carcinoma or follicular thyroid carcinoma. MAIN OUTCOME MEASURE: A logistic regression model was used to examine the relationship between various clinicopathologic parameters and the insular subtype. RESULTS: The insular subtype involved 14 of 127 tumors. Unlike extrathyroidal extension and nodal metastasis, primary tumor diameter (> 40 mm vs < or = 40 mm; P = .008) and distant metastasis (P = .003) correlated with the insular subtype. Both parameters were interrelated since tumors greater than 40 mm displayed distant metastasis more often (30% vs 8%; P = .008) than tumors measuring 40 mm or less. CONCLUSIONS: These findings suggest that an unidentified somatic event may induce an accelerated proliferation of the transformed thyrocytes, which may ultimately result in enhanced rates of distant metastasis with increasing tumor volume.

Adult↗

Prognostic significance of local recurrence in breast cancer after postmastectomy radiotherapy.

PURPOSE: We have retrospectively analyzed the impact of local recurrence in patients with adjuvant radiation therapy after mastectomy for breast cancer. PATIENTS AND METHODS: From January 1985 through December 1993, 959 patients were irradiated after mastectomy for breast cancer. The age ranged from 34 to 79 years, the median follow-up was 3.1 years (range: 0.3-12.2 years). 368 (38%) were pre- and 591 (62%) postmenopausal. 35% had T3-4 tumors, 62% had axillary lymph node involvement, and 66% received additional systemic hormonal and/or cytotoxic therapy. Postmastectomy radiotherapy was administered in case of positive axillary nodes and in high-risk pN0-patients. The chest wall and lymphatics (axilla, parasternal and supraclavicular nodes) were irradiated with an anterior photon field with 50 Gy and the chest wall with an electron field with 44 Gy in 2-Gy fractions. RESULTS: The overall survival was 70.5% after 5 and 59.8% after 10 years. 53 patients (5.5%) developed a locoregional recurrence 2-96 months after treatment (median 26 months). The local control rate was 92.7% after 5 and 86.4% after 10 years. Axillary lymph node involvement was the most important and (in a multivariate analysis the only) risk factor for local recurrence (p = 0.0001). Patients with local control had a significantly better 10-year distant-disease-free survival and overall survival as compared to patients with local recurrence (44.5% vs 15.4%, p = 0.002 and 62.1% vs 34.8%, p = 0.004). Local recurrence increased the risk of death by a factor of 1.7 and in a Cox regression model, axillary lymph node status, T-category and local recurrence were significant prognostic factors for overall survival. In patients with local recurrence, the initial axillary lymph node status was the most important prognostic factor for survival after local recurrence. The 3-year survival after local relapse was 86% for patients with pN0 status vs 27% in with positive axillary nodes (p = 0.025). CONCLUSIONS: Local recurrence after treatment of breast cancer with mastectomy + radiotherapy +/- systemic therapy is associated with a significantly higher risk of distant metastases and death. In this analysis, local recurrence was a strong and, besides lymph node status and T category, an independent risk factor for survival. Minimizing the risk of local recurrence is therefore an essential goal of a curative treatment concept.

Adult↗

Tumor hypoxia and systemic levels of vascular endothelial growth factor (VEGF) in head and neck cancers.

BACKGROUND: Hypoxia is the most important stimulus for the up-regulation of vascular endothelial growth factor (VEGF), one of the key cytokines for angiogenesis. We have investigated the possible relationship between tumor hypoxia and systemic levels of VEGF. PATIENTS AND METHODS: 56 patients with head and neck cancers underwent measurement of tumor volume (pretreatment CT scans), tumor oxygenation (pO2 histography) and serum levels of VEGF. The hemoglobin level ranged from 9.1 to 16 g/dl. The absolute amount of hypoxic tumor (hypoxic tumor volume) was determined as the product of the absolute tumor volume and the relative frequency of hypoxic (< 5 mm Hg) measurements in the pO2 histography. RESULTS: The serum VEGF levels in the 56 head and neck cancer patients ranged from 102 to 1699 pg/ml (median 405 pg/ml, mean 527 +/- 396 pg/ml). Elevated serum-VEGF levels (> 700 pg/ml) were found in 14/56 patients (25%). Serum-levels of VEGF were significantly and independently correlated with hypoxic tumor volume (R2 = 0.63, p < 0.001), but also with total tumor volume, hemoglobin levels, platelet counts and tumor hypoxia. There was no correlation with T and N category, histological grading, and age. CONCLUSIONS: The strong and independent impact of the hypoxic tumor volume on systemic VEGF levels suggests that the absolute amount of hypoxia within a tumor represents the most important stimulus for up-regulation of angiogenesis. Anemia acts as a co-factor via worsening of tumor tissue oxygenation.

Adult↗

[In vitro determination of the cytotoxic activity of saliva samples of smokers].

BACKGROUND: The question arised whether saliva can be included in populations monitoring of high risk groups for the development of head and neck squamous cell carcinomas. Cytotoxic mechanisms strongly influence the carcinogenesis of squamous cell carcinomas. PATIENTS AND METHODS: Saliva specimen of 131 abusing and non-abusing probands were tested on their biological (cytotoxic) effects to draw conclusions on the individual cancer risk. To determine the cytotoxic activity of saliva, we used the "plating efficiency index" of lungfibroblasts of the chinese hamster. RESULTS: We found significantly increased cytotoxic effects in the saliva of smoking probands (p < 0.002). Regularly combined smoking and drinking of alcohol led to a highly significant increased risk of cytotoxic saliva in the tested persons (odds ratio: 17.4; p < 0.005). CONCLUSIONS: Including patients with head and neck squamous cell carcinomas, ongoing studies must prove the practical relevance of this biomarker for estimating the relative cancer risk in the upper aerodigestive tract.

Adult↗

[Ames test as biomarker].

BACKGROUND AND OBJECTIVE: The incidence of squamous cell carcinomas in the upper aerodigestive tract has increased worldwide. The main risk factors are chronic tobacco and alcohol consumption. The detection of high-risk persons is important because early diagnosis of these tumors provides a good chance for permanent healing. Biomonitoring programs may help to give precise information about the individual cancer risk among smoking and drinking persons. The aim of this study was to evaluate the Ames test as a biomarker to detect the genotoxicity of saliva. PATIENTS AND METHODS: Saliva specimens of 131 probands were investigated for their genotoxic effects using the Ames test. RESULTS: Our results showed an increased trend of genotoxic activity in the saliva of smokers. A highly significant additional increase of genotoxicity was measured in smoking and drinking individuals. CONCLUSIONS: Our study shows that the Ames test could be used to show genotoxic effects in saliva specimens. In combination with other biomarkers, this test may help to develop a valid concept for detecting cancer-endangered people.

Adult↗

[Is diabetes in the elderly patient a risk factor for cataracts?].

The higher prevalence of diabetes for cataracts as a component of the multifactorial genesis of age-related cataracts has been proven in several epidemiological studies. Most of these results identified diabetes as a highly significant risk factor for cataracts in older diabetic males and females. The increased cataract risk of diabetics then decreases after the age of 65 years and is related to different types of opacity. In addition to the sorbitol pathway, diabetic hyperglycaemia causes increased formation of glucose-derived advanced glycation cytotoxic end-products. In connection with these specific pathological changes, the crucial role of the lens epithelium with respect to cataractogenesis is emphasised in several studies. The results of our own prospective clinical study proved the significantly lower mean cell density in type II diabetics compared with eyes from non-diabetics. Together with the other determined morphological cell characteristics, this result seems to be due to the cataractogenic influence of diabetic metabolic disorders on the lens There are some indications for the primary cataractogenic importance of the lens epithelium in type II diabetes.

Adult↗

Thyroid carcinoma invading the cervicovisceral axis: routes of invasion and clinical implications.

BACKGROUND: Controversy exists about the routes of invasion (extrathyroidal versus lymphogenic extension) when differentiated carcinoma (DTC) and medullary thyroid carcinoma (MTC) invade the cervicovisceral axis (ie, larynx, trachea, esophagus). METHODS: We carried out an institutional analysis, from November 1994 to October 1999, of 451 consecutive patients undergoing surgery for DTC and MTC. RESULTS: Irrespective of tumor entity, carcinomas with cervicovisceral invasion (n = 34) were significantly larger and displayed higher pT categories (mainly pT4) than noninvasive carcinomas. In invasive papillary thyroid carcinoma (PTC) and MTC, the rates of positive lymph nodes were significantly higher than in noninvasive controls. When separate logistic regression analyses were fitted for laryngeal, tracheal, and esophageal invasion, extrathyroidal growth (pT4) consistently was a significant factor predictive of invasion in both DTC and MTC, with relative risks of 10.9 to 67.8. As the routes of invasion are similar in DTC and MTC, all data were pooled for multivariate analyses. Herein, the pN1 category had a significant impact only on esophageal invasion, with a relative risk of 4.7. CONCLUSIONS: Invasion of the cervicovisceral axis is more often caused by extrathyroidal growth than by nodal metastasis. To keep nodal metastasis from encroaching onto the cervicovisceral axis, paratracheal and paraesophageal lymph nodes should be cleared from the cervicocentral compartment at the primary operation.

Carcinoma, Medullary↗

Extended surgery and early postoperative radiotherapy for undifferentiated thyroid carcinoma.

The current study was devised to evaluate the therapeutic potential of extended surgery for improving survival in undifferentiated thyroid carcinoma (UTC). An institutional retrospective survival analysis (July 1994 to December 1998) of 30 patients who underwent surgery for UTC with locally curative intent was done. Median and 1-year survival was 4 months and 37%, respectively. Primary patients were older (70 vs. 59 years; p = 0.026) and deceased earlier (median survival 4 vs. 20 months; p = 0.027, log-rank test) than their reoperative counterparts, suggesting a referral bias toward younger patients. Survival analysis was restricted to primary pT4 UTC, leaving 18 patients. On univariate analysis, pN and M category, degree of resection (R2 versus R0/1 and radiotherapy (0-30 Gy versus >30 Gy) were identified as parameters suitable for further testing. On multivariate analysis, pN1 was a significant prognosticator of decreased survival (RR = 5.9; p = 0.043), followed by R2 (RR = 4.1, p = 0.088) and M1 (RR = 3.6; p = 0.089). Because of low patient numbers after stratification for radiotherapy, only pN and degree of resection were analyzed on subsequent multivariate analysis. In the incomplete radiotherapy stratum, neither of the two parameters affected survival, whereas R2 and pN1 limited survival in the complete radiotherapy stratum. In primary pT4 UTC, a subset of pN0 patients with R0/1 resections and radiotherapy greater than 30 Gy seemed to benefit from extended surgery. Because pN1 and R2 patients with radiotherapy of 30 Gy or less comprised most UTC patients, only 1-year, but not median, survival improved compared to literature controls.

Aged↗

Prophylactic completion thyroidectomy for differentiated thyroid carcinoma: prediction of extrathyroidal soft tissue infiltrates.

Controversy exists on the extent of completion surgery for differentiated thyroid carcinoma (DTC). Between November 1994 and October 1999, 88 consecutive DTC patients who had no evidence of residual tumor after primary surgery underwent completion total thyroidectomy in conjunction with a systematic en bloc resection of the cervicocentral lymph node compartment. To identify individual parameters predictive of occult residual tumor, three separate logistic regression analyses were fitted for intrathyroidal tumor, extrathyroidal soft tissue infiltrate and cervicocentral nodal metastasis. Altogether, occult residual tumor was found in 22% (19/88) of patients. Occult intrathyroidal tumor, extrathyroidal soft tissue infiltrate, and cervicocentral nodal metastasis were encountered in 11%, (10/88), 6% (5/88), and 10% (9/88), respectively. On logistic regression analysis, patients with multifocal DTC on primary surgery had a 17.4 times higher risk (p = 0.026) on reoperation to harbor extrathyroidal soft tissue infiltrates within the cervicocentral compartment. At least in multifocal DTC, a systematic en bloc resection of the thyroid remnant and cervicocentral lymph node compartment is warranted to ensure clearance of occult extrathyroidal soft tissue infiltrates, setting the stage for radioiodine therapy. Selective lymph node dissection alone does not seem capable of eliminating these soft tissue infiltrates from the cervicocentral compartment.

Humans↗

[Association between elevated serum VEGF and polarographically measured tumor hypoxia in head and neck carcinomas].

PURPOSE: Clinical investigation of a potential relationship between VEGF concentration in serum (sVEGF) and polarographically measured tumor oxygenation in patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: In 56 patients with SCCHN we estimated the classical tumor parameters, the sVEGF concentration (immunoassay) and the tumor oxygenation (Eppendorf pO2 histograph). The platelet count and the tumor volume were evaluated simultaneously. RESULTS: In a unifactorial analysis the total volume (132 cm3 vs. 38 cm3), the hypoxic subvolume (HSV = total volume multiplied with the relative frequency of values < or = 5 mm Hg/63 cm3 vs. 10 cm3) and the platelet count (380 10(9)/l vs. 271 10(9)/l) were significantly higher in the patient group with a sVEGF level > 707 pg/ml compared to the group with a sVEGF below this threshold. The multifactorial analysis confirmed significant effects for the hypoxic subvolume and the platelet count. Regarding hypoxic subvolume and sVEGF as continuous parameters a significantly positive correlation was found. This correlation remained somewhat weaker but significant after inclusion of the platelet count as covariate. CONCLUSION: On base of our data a clinical association between elevated sVEGF and polarographically measured tumor hypoxia could be confirmed. This was possible considering not only the relative grade of hypoxia but also the absolute amount of hypoxic regions. The VEGF released from platelets during blood clotting influences the sVEGF level essentially, however, the hypoxia effect was not completely deleted. Due to the platelet effect an estimation of sVEGF is not able to substitute polarographical measurement of tumor pO2. Therefore in an ongoing study we investigate whether VEGF values estimated in plasma are better correlated with the polarographically measured tumor pO2 than serum VEGF levels.

Adult↗

Flow cytometric analysis of DNA content and proliferation and immunohistochemical staining of Ki-67 in non-small cell lung cancer.

BACKGROUND: The aim of our study was to examine the significance of tumour DNA-content and proliferation in lung cancer. METHODS: The DNA content and S-phase fraction (SPF) was determined by flow cytometry in 125 resected tumours of patients with non-small cell lung cancer. In 40 cases we compared the SPF with immunohistochemical staining of the Ki-67 protein using MIB-1 antibody. RESULTS: DNA aneuploidy was detected in 84.8% (106/125). Cell cycle analysis for the determination of proliferation activity was only possible in 69 (55.2%) cases. An SPF of 0-8% as a sign of low proliferation was found in 27 specimens. In advanced tumours at stage III and IV the proportion of tumours with SPF 9-16% was significantly (p<0.05) increased as compared to tumours at stage I and II. There was a significant correlation (p=0.012, ascent: 0.045) between SPF and MIB-1. Patients with aneuploid tumours had a relative risk of 1.4 to die earlier than patients with diploid tumours. Patients with SPF of 9-16% in the tumour tended to decreased survival (5-year survival rate: 29%) in correlation to patients with a percentage of SPF 0-8% (5-year survival rate: 38%, p=0.5). These differences were significant (p=0.048) in patients with adenocarcinomas only. In the multivariate COX-regression model age (p=0.03) and stage (p=0.0001) were significant prognostic factors, ploidy state (p=0.33) was of no prognostic significance. CONCLUSIONS: Flow cytometry seems to be a useful method for understanding the clinical behaviour of lung cancer. Especially the SPF in adenocarcinomas may be used as a prognostic indicator.

Analysis of Variance↗