Biomedical subjects

P Würl

Publications and source records attributed to P Würl.

At least 37 records · Page 2Linked to original sources

PubMed2001

[Luxation of the clavicle as rare cause of monstrous thrombus formation of the internal jugular vein].

Summary.A 55-year-old female with massive painless swelling of the right cervical soft tissue was admitted for surgical exploration. The operation revealed an ectasia of the internal jugular vein with a diameter up to 7 cm which was obliterated by thrombotic material. We discussed a retrosternal dislocation of the clavicle proved by chest X-ray. We resected the internal jugular vein from the basis of the skull to the upper thoracic aperture. The postoperative course was uneventful.

Clavicle↗

PubMed2000

A MboII polymorphism in exon 11 of the human MDM2 gene occuring in normal blood donors and in soft tissue sarcoma patients: an indication for an increased cancer susceptibility?

The human MDM2 oncogene, well known as the tumor suppressor gene p53's partner, plays an important role in tumorigenesis whether it is dependent on or independent of TP53. In this study, we investigated in a PCR-sequencing analysis the exon 11 of the human MDM2 gene for gene alterations. A MboII polymorphism occurs in 8% of normal blood donors (8 out of 100 probands) and in 13% of the soft tissue sarcoma patients (11 out of 82 patients). Of note was that two STS patients carried the gene alteration only in the tumor specimens heterozygously but not in normal tissue. In a Kaplan-Meier analysis, patients without the polymorphism, indicated a median survival rate of 57 months, whereas, patients with the polymorphism survived on average only 38 months. We suggest that this polymorphism might be associated with an increased cancer susceptibility.

Base Sequence↗

PubMed2000

Gains in chromosomes 7, 8q, 15q and 17q are characteristic changes in malignant but not in benign peripheral nerve sheath tumors from patients with Recklinghausen's disease.

In order to investigate typical genomic alterations in patients with Recklinghausen's disease (NF1) we studied one from each of the six patients with NF1 several benign and/or malignant tumors. By means of comparative genomic hybridization (CGH) gained results from six benign neurofibromas and 14 malignant peripheral nerve sheath tumors (MPNSTs) were compared with four benign peripheral nerve sheath tumors (BPNSTs) from patients without NF1. In all 14 MPNSTs DNA sequence copy number changes were detected with a mean value of 13.5 imbalances per sample. The most frequent gains were in 8q, 17q (12 tumors each), 7p, 15q (ten tumors each), and 7q (nine tumors). We found ten high-level amplifications in nine of the 14 samples. In two cases, the high-level amplification involved 7p14-pter and 17q24-qter as well. The most frequent loss was in 17p (seven tumors). The benign neurofibromas from NF1-patients and the sporadic BPNSTs revealed only partially DNA sequence copy number changes without any distinct pattern. The gains of #7, 8q, 15q, and 17q were found exclusively in MPNSTs but not in neurofibromas and are supposed to be associated with malignant tumor progression. In comparison of the results of the 14 MPNSTs from NF1-patients with the results of previously published 20 sporadic MPNSTs, we found that the gain of 8q occurs most frequently in both tumor groups. Of course additionally in the sporadic MPNSTs there were more frequent gains of 5p, #6, and statistically significant gains of 20q. On the other hand in the MPNSTs from NF1-patients the most frequent gains were found in #7, and statistically significant in 15q, and 17q.

Adult↗

PubMed2000

Colony formation of soft tissue sarcoma cells is inhibited by lipid-mediated antisense oligodeoxynucleotides targeting the human mdm2 oncogene.

More than one third of human soft tissue sarcoma (STS) have elevated levels of the MDM2 oncoprotein, resulting either from gene amplification or alternate mechanisms. MDM2 functions as a negative feedback regulator of the tumor suppressor p53. The aim of the present study was to investigate whether mdm2-antisense oligodeoxyribonucleotides (AS-ODNs) can influence the growth characteristics of two MDM2-overexpressing STS cell lines (US8-93, LMS6-93) where both have heterozygous p53 non-missense mutations. Cells were treated with lipofectamine-complexed mdm2 AS-ODNs complementary to a sequence of the mdm2 cDNA initiation site in comparison to sense control ODNs. After seeding and cultivation of a defined cell number the clonogenic survival was performed. The treatment of US8-93 cells with AS-ODNs, but not with sense ODNs, decreased the number of colonies up to > 80%. Western blot analysis demonstrated a significant decreasing of MDM2 protein level in AS-ODN transfected cells indicating an AS-specific inhibition of mdm2 transcription in US8-93 cells. Additionally, an increase of the G2/M population was found. In contrast, in the LMS6-93 cells treated with AS-ODNs only a decrease in clonogenic survival up to 26%, no change in MDM2 protein level and no cell cycle alterations were seen. All these factors taken together into consideration can be suggest that lipid-mediated mdm2 AS-ODNs could be as an effective therapeutic strategy for STS with an abnormal mdm2 overexpression.

Cell Division↗

PubMed2000

[The radiological and surgical management of nonpalpable breast lesions].

In this retrospective study the results of surgical biopsy of suspected breast cancer in 319 outpatients are reported. In 113 cases (35.4%) the lesion was palpable, in 206 cases (64.6%) it was not. Concerning the nonpalpable lesions, mammography was performed in 98 patients (47.6%) for work-up of fibrocystic changes, in 41 patients (19.9%) for initial participation in a breast cancer prevention program, and in 33 patients (16.0%) for surveillance after breast conservation therapy. Prior to operation, 84.0% (n = 173) of the nonpalpable lesions were detected by mammography, 11.2% (n = 23) by sonography, and 4.8% (n = 10) by magnetic resonance imaging. Intra-operative specimen mammography was carried out in every case detected by mammography. In 19.4% (n = 40) of 206 nonpalpable lesions a malignant tumor was found. Twenty-five percent (n = 10) of all marked tumors were diagnosed and treated as in-situ stage tumors, while 65% (n = 26) were diagnosed and treated as tumors in the pT1 stage. As regards the nodal stage, 85% (n = 34) of the tumors were diagnosed and treated as pNO tumors, and 100% (n = 40) were found to be free from any distant metastases. Consequently, for improving prognosis and, at the same time, for reducing the rate of breast amputations as a means of curative therapy of breast cancer, regular screening in defined risk groups is necessary. Surgical treatment of patients with small and nonpalpable findings should be reserved for departments with marking and quick-freezing facilities.

Adolescent↗

PubMed2000

Cytokeratin-positive cells in bone marrow in comparison with other prognostic factors in colon carcinoma.

BACKGROUND AND AIMS: Despite the use of radical locoregional therapeutic methods and although conventional methods of diagnosis give no indication of metastases at the time of operation, distant metastases develop in approximately 50% of carcinoma patients within 5 years. While local relapses after the R0 resection of solid tumors are mainly a matter of concern for the surgeon, distant metastases can be traced back to the systemic dissemination of tumor cells at the time of operation. PATIENTS/METHODS: A prospective study is presented in which 145 patients suffering from colon carcinoma were analyzed for the prognostic relevance of isolated disseminated tumor cells detected in the bone marrow (IDT BM). The patients were operated on between 1993 and 1997 and subsequently observed until 1999. RESULTS: The monoclonal antibody A45-B/B3 was used with the immunocytochemical standard method for detecting IDT BM. For the purpose of cell cultivation, the cells were marked with the HEA-125 antibody and separated by means of magnetic cell sorting (MACS). CONCLUSION: In this investigation the presence of isolated disseminated tumor cells, as indicated by the A45-B/B3 antibody, proved to be an independent prognostic factor for survival time. The risk of an earlier death increased in node-negative and metastases-free patients with the detection of IDT BM by a factor of 12.60. The detection of IDT BM also represented an independent prognostic factor for the time until advancement of the tumor. The risk of an earlier relapse increased with the detection of disseminated tumor cells in the bone marrow containing the A45-B/B3 antibody by a factor of 18.02. A generally acknowledged standardization of the method is desirable. Due to the importance of the independent prognostic IDT BM factor, this method of ascertaining the pathological stage should be established at institutions of higher learning.

Aged↗

PubMed2000

The p53 status in juvenile chronic arthritis and rheumatoid arthritis.

The aim of this study was to investigate the p53 status in two autoimmune diseases; juvenile chronic arthritis (JCA) and rheumatoid arthritis (RA). In a PCR-sequencing analysis of exons 4-9 of the p53 gene, no mutation was identified, except for the case of an RA synovectomy sample with two mutations of intron 7. p53 gene polymorphisms for codons 36, 47, and 213 were not detected. Codon 72 polymorphism showed an indication of an increased occurrence of the Pro/Pro allelotype in JCA. Expression of P53 protein was comparable for JCA and RA synovectomy samples. For all RA samples P53 protein was detectable, whereas one sample of a JCA patient failed to express P53 protein.

Adolescent↗

PubMed2000

[Improved prognosis in breast carcinoma by excision of non-palpable carcinoma-suspected lesions. Analysis of 319 ambulatory surgery operations].

A retrospective study is described according to which 319 outpatients had been operated on for suspected carcinoma because of breast lesion, in the course of three years in this hospital. In 113 cases (35.4%) the lesion was palpable, in 206 cases (64.6%) it was not. In the non-palpable cases, mammography was indicated in 98 patients (47.6%) undergoing controls for mastopathy, in 41 patients (19.9%) undergoing a first mammography in the course of preventive check-ups, and in 33 patients (16.0%) undergoing a check-up after operative therapy of breast cancer. Prior to operation, 84.0% (n = 173) of the non-palpable lesions were marked by mammography, 11.2% (n = 23) by sonography, and 4.8% (n = 10) by magnet resonance imaging (MRI). Intraoperative specimen mammography was made in every case marked by mammography. In 19.4% (n = 40) out of the 206 cases of marked though non-palpable focuses a tumour was found. 25% (n = 10) of all marked tumours were diagnosed and treated as in-situ stage tumours, 65% (n = 26) were diagnosed and treated as tumours in the pT1 stage. As regards the nodal stage, 85% (n = 34) of the tumours were diagnosed and treated as being pN0 tumours, and 100% (n = 40) were found to be free from any distant metastases. Consequently, for improving prognosis and, at the same time, for reducing the rate of breast amputations as a means of curative therapy of breast cancer, regular screening in defined risk groups is necessary. Surgical treatment of patients with small and non-palpable findings should be reserved for departments with marking and quick-freezing facilities.

Adolescent↗

PubMed2000

Detection of cytokeratin-positive cells in bone marrow in breast cancer and colorectal carcinoma in comparison with other factors of prognosis.

A prospective study is presented in which 293 patients suffering from breast cancer and colorectal carcinoma were analyzed for prognostic relevance of detected isolated disseminated tumor cells in bone marrow (IDTBM). The patients underwent surgery in the period from 1995 to 1997 and remained under observation until 1999. The monoclonal antibody A 45-B/B3 was used in the standard immuno-cytochemical method for detecting IDTBM, which represented an independent prognostic factor for survival time in patients with breast cancer or colorectal cancer. In breast cancer, when IDTBM were detected, the survival period was reduced by at least half. When disseminated tumor cells containing the A45-B/B3 antibody were detected in bone marrow, the risk of an earlier relapse of the tumor increased at least fourfold. In colorectal cancer, detection of IDTBM reduced survival time by a factor of 1.2-4.3. The risk of earlier relapse increased when disseminated tumor cells containing the A45-B/B3 antibody were detected in bone marrow by 2.8-8.1. Therefore, the use of IDTBM as an independent prognostic factor would provide an important method for determining the pathological stage of various cancers. Standardization of this technique into a generally accepted method would be especially desirable in treatment of patients with breast or colorectal cancer.

Actuarial Analysis↗

PubMed2000

mdm2 mRNA level is a prognostic factor in soft tissue sarcoma.

BACKGROUND: The oncogenic properties of murine double minute-2 (mdm2) protein over-expression, which mostly results from the interaction with the tumor suppressor p53, are well described and their negative impacts on the prognosis of affected patients is well characterized. However, clinical relevance of mdm2 mRNA expression is poorly investigated. MATERIALS AND METHODS: In this study, 65 soft tissue sarcoma (STS) samples were analyzed for mdm2 mRNA expression by a quantitative reverse transcription polymerase chain reaction (RT-PCR) approach using available validated ready-to-use assays based on the TaqMan technology (PE Applied Biosystems, Weiterstadt, Germany). Mdm2 data were correlated to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression calculated from the same sample. RESULTS: For patients with a mdm2/GAPDH mRNA ratio below 50 zmol/amol the survival was strikingly reduced in comparison to patients with a ratio of > or =50 (p = 0.0241). Multivariate Cox analysis showed that the difference in prognosis for patients with tumor stage 2 and 3 became even more pronounced between patients with a ratio of <50 zmol/amol and patients with a ratio of > or =50 (p = 0.0041; RR = 5.6). To test if the group with an mdm2 mRNA expression > or =50 is homogenous concerning the prognosis, the group was divided into three subgroups with values of 50 to <100, 100 to <500 and > or =500. The subgroup with values of 100 to <500 showed the best prognosis (p = 0.0164); whereas, the one with values of 50 to <100 showed the worst prognosis in this group and, in between, was the one with values of > or =500. After omitting patients of stage 1 and 4, the subgroup with values of 100 to <500 showed an even more striking best prognosis (p = 0.0015); the other subgroups remained in the same sequence. The risk of tumor-related death over 5 years was most conspicuous in patients with mdm2 mRNA expression <50 than in those with ratios of 100 to <500 displaying a 13.3-fold higher risk. In a comparison between mdm2 mRNA levels and P53 protein expression or p53 mutational status, no relationship was found. CONCLUSIONS: In our study, the mdm2 mRNA level appears to be an independent prognostic factor for STS patients, marking its role in STS genesis and as a potential factor for gene therapeutical approaches.

DNA Mutational Analysis↗

PubMed2000

[Monstrous venous hemangioma of the retroperitoneum: problems of diagnosis].

The venal haemangioma is defined as a benign tumor consisting of veinlike vessels. The preoperative diagnosis and its inherent problems are illustrated using a coincidentally diagnosed monstrous haemangioma tumor of the retroperitonial space in a twenty year old patient. With respect to our patient, X-ray, computer tomography and angiography all failed as diagnostic tools. Only the use of Doppler sonographic flow signals suggested the presence of a haemangioma. The morphology, prognosis and clinical significance of blood vessel tumors are multifaceted. The most important differential diagnoses to the venous haemangioma are the cavernous and the capilliary haemangioma. The venous haemangioma distinguishes itself through the presence of blood vessel walls. Haemangiomas are common benign tumors. In the presence of highly developed muscular components, there exists a transition to angiomyomas and to leiomyomas. Venal haemangiomas are extremely rare in the demonstrated localisation of the retroperitoneal space. Here they can grow to monstrous preportions whilst remaining undetected. Thus the patient is under the potential danger of bleeding to death through trivial injuries. The therapy of choice remains total surgical excision. In situations of unclear clinical results with respect to preoperative diagnosis especially amongst young adults, one should at least consider the possibility of a haemangioma as the root of the problem.

Adult↗

PubMed2000

[Hepatocellular carcinoma in an additional pedunculated liver lobe in the lower abdomen: differential diagnosis problems].

The case described is that of a 36 years old patient with a known tumor in her lower abdominal cavity which has been observed to increase in size for the passed 16 years. Intraoperatively, one observed a very rare finding of an extra liver lobe of the left liver lobe and located in the lower abdominal cavity. Located within is a multifocal therapeutically treatable hepatocellular cancer.

Adult↗

PubMed2000

[Quality assurance in excision of suspected malignant, preoperatively marked and unmarked, breast lesions. A one-year analysis].

The breast cancer incidence is increasing for all industrial countries in the last years. Therefore the relevance of screening methods especially of mammography for early registration of suspected lesions becomes more and more important. One result of using screening methods is an increased rate of patients with lesions which are suspected for cancer but non palpable. For the background of that fact we are describing our one year experience with the therapy of cancer suspected breast lesions in 136 female patients. In 47 cases (34.6%) there was a palpable and in 89 cases (65.4%) a non-palpable lesion. The need for mammography was assured in 43 patients (48.3%) through mastopathic controls, in 23 patients (25.8%) within the frame work of a preventive first mammography and in 15 patients (16.8%) through controls after operative therapy for breast cancer. All non-palpable lesions were marked preoperatively through mammography 88.8% (n = 79), sonography 6.7% (n = 6), or through magnet resonance imaging MRI 4.7% (n = 4). Every mammographic marked case was followed by an intraoperative specimen mammography. In 16.8% (n = 15 from 89) of the non-palpable marked areas, a carcinoma was found. 16.7% (n = 3) of the detected cancers were diagnosed in an in-situ-stage, all others in an early stage (pT1-, pN0-, M0-stage) and treated. Besides the early diagnosis of breast cancer and the resulted improvement of prognosis also the rate of breast saving therapies can be increased. Reflecting our datas it should be demanded a regular screening for defined risk groups. In conclusion to improve the prognosis of breast cancer patients and reduce the risk of ablative therapies it is necessary to release a consequent marking of non-palpable cancer suspected breast lesions, a consequent aseptic handling before operation, an intraoperative mammography of the resected area and a frozen section.

Adolescent↗

PubMed2000

Rating of isolated disseminated tumor cells in bone marrow in comparison with other factors of prognosis in breast carcinoma.

BACKGROUND: Despite the use of radical loco-regional therapeutic methods and although conventional methods of diagnosis give no indication of metastases at the time of operation, distant metastases develop in approximately 50 percent of the carcinoma patients within 5 years. While with the R0 resection of solid tumors local relapses are mainly a matter of concern for the operating surgeon, distant metastases can be traced back to systemic dissemination of tumor cells at the time of operation. AIMS: The goal of our prospective six year continuous study is to compare the rating of the IDT BM with established prognosis factors and to reach conclusions for the practice. METHODS: A prospective study is represented in which 197 patients suffering from breast carcinoma were analyzed for prognostic relevance of detected isolated disseminated tumor cells in the bone marrow (IDT BM). The patients were operated between 1993-1997 and subsequently observed until 1999. The monoclonal antibodies CK II and A45-B/B3 were used with the immuno-cytochemical standard method for detecting IDT BM. For the purpose of cell cultivation, the cells were marked with the HEA 125 antibody and separated by means of magnetic cell sorting (MACS). In this investigation, only the presence of isolated disseminated tumor cells detected by the RESULTS: A45-B/B3 antibody proved to be an independent prognostic factor for survival time. The risk of an earlier death increased with the detection of IDT BM at least by a factor of two. The detection of IDT BM also represented an independent prognostic factor for the time until advancement of the tumor. The risk of an earlier relapse of the tumor increased with the detection of disseminated tumor cells in the bone marrow containing the A45-B/B3 antibody by at least a factor of four. CONCLUSION: A generally acknowledged standardization of the method is desirable. Due to the importance of the independent prognostic IDT BM factor, this method of ascertaining the pathological stage should be established at institutions of higher learning.

Aged↗

PubMed1999

Clinical relevance of pRb and p53 co-overexpression in soft tissue sarcomas.

The goal of this study was to examine the relationship between immunohistochemical pRb detectability and p53 overexpression in 198 soft tissue sarcomas (STS) with regard to its clinical relevance. Distinct pRb detectability multivariately shows a correlation to survival rate (relative risk (RR)=1.59, P=0.037). p53 positivity was also multivariately correlated to poor prognosis (RR=2.17, P=0.0014). Stratification of pRb staining to p53 results shows a prognostical graduation. Patients with negativity for both proteins have the most favorable prognosis (projected 5-year survival rate (psr)=54.5%). In contrast to this, positivity for both antibodies has the highest risk (RR=2.48, P=0.02) and the poorest prognosis (psr=17.4%). To conclude, these results explain that the clinical relevance of immunohistochemical pRb positivity in STS is connected with p53 in the form of having an increasing effect on the known prognostic relevance of p53 overexpression.

Adolescent↗

PubMed1999

Assessment of genomic imbalances in malignant fibrous histiocytomas by comparative genomic hybridization.

In order to investigate genomic imbalances, comparative genomic hybridization was applied to 20 malignant fibrous histiocytomas. Deletions were rare and found mainly in chromosomes 2q33-35, 4q32-qter, 8p, 9p21-pter, 12p and 19p, whereas, over-representations frequently affected chromosomes 3, 4q31, 5p, 6, 7, 14q22-ter, 18p, as well as, five distinct amplifications within the regions 12q12-15 and 15q24-qter. The total number of genetic imbalances per tumor was slightly increased in primary tumors when compared to relapses. No relationship was found between the patterns of gain and loss when compared to the histological subtype, tumor grading, the clinical outcome and the p53 mutation status.

Aneuploidy↗

PubMed1999

Genomic imbalances of 7p and 17q in malignant peripheral nerve sheath tumors are clinically relevant.

We investigated 31 malignant peripheral nerve sheath tumors (MPNSTs) from 23 patients by means of comparative genomic hybridization (CGH) in order to study quantitative genomic aberrations of these tumors. Twenty-one of the 23 patients revealed changes, with a mean value of 11 aberrations per sample (range 2-29). The minimal common regions of the most frequent gains were 8q23-q24.1 (12 cases), 5p14 (11 cases), and 6p22-pter, 7p15-p21, 7q32-q35, 8q21.1-q22, 8q24.2-qter, and 17q22-qter (10 cases each). Seventeen high-level amplifications were detected in eight of the 21 samples. In three cases, the high-level amplifications involved 8q24.1-qter, and in two cases each the high-level amplifications involved regions 5p14, 7p14-pter, 8q21.1-q23, and 13q32-q33. The minimal common region of frequent losses was 14q24.3-qter (five cases). The gain of 8q as a single common change in the primary tumor, the recurrence, and the metastasis from the same patient suggests that this aberration is an early change in the tumorigenesis of MPNSTs. Comparable aberrations were observed in separate tumors of the same patients affected by Recklinghausen's disease, indicating a limited number of accidental secondary changes. In sporadic MPNSTs, the most frequent gains were narrowed down predominantly to 5p, 6, 8q, and 20q, whereas in MPNSTs from patients with Recklinghausen's disease, there was most often a gain in 7q, 8q, 15q, and 17q. The occurrence of gain of both 7p15-p21 and 17q22-qter was associated with a statistically significant poor overall survival rate (P = 0.0096).

Adolescent↗

PubMed1999

[Monstrous venous hemangioma of the retroperitoneum. Problems in diagnosis].

The venous haemangioma is defined as a benign tumor consisting of vein-like vessels. The preoperative diagnosis and its inherent problems are illustrated by a coincidentally diagnosed monstrous haemangioma of the retroperitoneal space in a twenty year old patient. With respect to our patient, X-ray, computed tomography and angiography all failed as diagnostic tools. Only the use of Doppler-sonographic flow signals suggested the presence of an haemangioma. The morphology, prognosis and clinical significance of blood vessel tumors are manifold. The most important differential diagnoses of venous haemangioma are the cavernous and the capilliary haemangioma. The venous haemangioma distinguishes itself through the presence of blood vessel walls. Haemangiomas are common benign tumors. They can grow to monstrous proportions whilst remaining undetected. Thus the patient is endangered of bleeding to death because of trivial injuries. The therapy of choice consists in total surgical excision. In unclear clinical situations with respect to preoperative diagnosis especially amongst young adults, the diagnosis of an hemangioma should be taken into amount.

Adult↗