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M Schwarzbach

Publications and source records attributed to M Schwarzbach.

At least 19 recordsLinked to original sources
PubMed2005

The location of KIT and PDGFRA gene mutations in gastrointestinal stromal tumours is site and phenotype associated.

AIMS: To assess the relation between KIT and PDGFRA mutations and the site of origin, histological phenotype, and pathomorphologically determined risk assessment in gastrointestinal stromal tumours (GISTs). METHODS: A series of 83 clinicopathologically characterised GISTs from 79 patients was analysed for KIT and PDGFRA mutations by polymerase chain reaction amplification, single strand conformation polymorphism analysis, and direct DNA sequencing. RESULTS: KIT or PDGFRA mutations were found in 57 and 11 GISTs, respectively. Most KIT mutations involved exon 11 (46 cases), followed by exon 9 (10 cases). The PDGFRA mutations mostly affected exon 18 (eight cases), followed by exon 12 (three cases). There was a significant association between KIT exon 9 mutations and an intestinal origin of GISTs, and between PDGFRA mutations and gastric origin of the tumours. In addition, the presence of PDGFRA mutations was significantly associated with epithelioid/mixed histology, as was the absence of identified receptor tyrosine kinase mutations. Vice versa, KIT exon 11 mutations were almost exclusively found in spindle cell GISTs. Furthermore, the presence of any KIT and PDGFRA mutations and the presence of KIT mutations alone were significantly associated with high risk/malignant GISTs. CONCLUSIONS: The location of KIT and PDGFRA mutations in GISTs is associated with the site of origin and histological phenotype. Genotyping of GISTs may be a helpful additional parameter in determining the biological profile of these tumours.

Adolescent↗
PubMed2004

[Intraluminal mass lesions of the thoracic aorta].

Aortic intraluminal mass lesions of the thoracic aorta are rare disorders with a wide range of differential diagnoses. Generalized hypercoagulation or vascular endothelial disorders have been proposed as the main etiological factor. The risk of catheter-related thrombus development or embolization after interventional procedures is as high as 17%. Malignancies of the aorta are somewhat rare. In some cases, the specific source of the thrombus could not be determined. Mainly, intraluminal tumors of the thoracic aorta become evident through peripheral embolization. Modern diagnostic tools are able to identify the structure and location of intravascular formations. Therapy options are influenced, due to the heterogenic entity, by the individual risk to the patient and the pathology of the thrombus.

Aorta, Thoracic↗
PubMed2003

Evaluation of F18-deoxyglucose positron emission tomography (FDG-PET) to assess the nature of neurogenic tumours.

AIMS: Benign neurofibromas and malignant peripheral nerve sheath tumours (MPNST) commonly develop in patients with neurofibromatosis. Differentiation of benign from malignant tumours by conventional preoperative imaging is unreliable. FDG-PET is a non-invasive technique for biological tumour evaluation. The aim of this study was to assess the value of FDG-PET in patients with neurogenic tumours suspicious for MPNST. METHODS: Benign and malignant neurogenic soft tissue tumours were prospectively evaluated by computed tomography or magnetic resonance imaging. Three-dimensional qualitative and quantitative FDG-PET was performed. Standard uptake value (SUV) was analyzed with respect to histological diagnosis and follow-up data. RESULTS: Twenty-five neurogenic soft tissue tumours were included. FDG-PET identified all primary (n=6) and recurrent MPNST (n=7). Benign lesions (n=12) did not demonstrate high FDG uptake. The SUV was significantly higher in MPNST (median 2.9; range 1.8-12.3), than in benign tumours (median 1.1; range 0.5-1.8) (p<0.001). At a cut-off value of 1.8 SUV measured 1 h post-injection FDG-PET distinguished between MPNST and benign neurogenic tumours with 100% sensitivity and 83% specificity. CONCLUSIONS: FDG-PET allows discrimination of benign from malignant neurogenic tumours. This should be particularly useful in patients with neurofibromatosis as FDG-PET may help to avoid multiple surgical procedures for benign tumours.

Adult↗
PubMed2001

Dynamic PET 18F-FDG studies in patients with primary and recurrent soft-tissue sarcomas: impact on diagnosis and correlation with grading.

UNLABELLED: The purpose of this study was to evaluate (18)F-FDG PET studies of primary and recurrent sarcomas for diagnosis and correlation with grading. METHODS: The evaluation included 56 patients, 43 with histologically proven malignancies and 13 with benign lesions. Seventeen patients were referred with suspicion on a primary tumor, and the remaining 39 were referred with suspicion on a recurrent tumor. The FDG studies were accomplished as a dynamic series for 60 min. The evaluation of the FDG kinetics was performed using the following parameters: standardized uptake value (SUV), global influx, computation of the transport constants K1-k4 with consideration of the distribution volume (VB) according to a two-tissue-compartment model, and fractal dimension based on the box-counting procedure (parameter for the inhomogeneity of the tumors). RESULTS: Visual evaluation revealed a sensitivity of 76.2%, a specificity of 42.9%, and an accuracy of 67.9%. The vascular fraction VB and the SUV were higher in malignant tumors compared with benign lesions (t test, P < 0.05). Although the FDG SUV helped to distinguish benign and malignant tumors, there was some overlap, which limited the diagnostic accuracy. The SUV and fractal dimension accounted for significant differences in six of the nine diagnostic pairs. Whereas grade (G) II and G III tumors were differentiated from lipomas on the basis of the fractal dimension and some other kinetic parameters, no differences were found between G I tumors and lipomas. On the basis of the discriminant analysis, the differentiation of soft-tissue tumors was best for the use of six parameters of the FDG kinetics (SUV, VB, K1, k3, influx, and fractal dimension). Eighty-four percent of G III tumors, 37.5% of G II tumors, 80% of G I tumors, 50% of lipomas, and 14.3% of scars could be classified correctly, whereas inflammatory lesions were misclassified. CONCLUSION: FDG PET should be used preferentially for monitoring patients with G III sarcomas. Visual analysis provides a low specificity. In contrast, the evaluation of the full FDG kinetics provides superior information, particularly for the discrimination of G I and G III tumors (positive predictive value, >80%).

Diagnosis, Differential↗
PubMed2000

[Results of oncological reoperation in primary soft tissue sarcomas].

BACKGROUND: Soft tissue sarcomas (STS) are frequently resected incompletely or without an adequate margin. In such clinical situations an oncological re-resection (wide or compartmental resection or amputation) is recommended. Here, we evaluate the results of oncological re-resection for STS. METHODS: Prospectively gathered data on 67 patients who underwent oncological re-resection after inadequate (intracapsular or marginal) surgery for primary soft tissue sarcomas were analyzed. RESULTS: STS were located in the extremities (85%) and trunk (15%). Advanced UICC stages (1992, 4th edn., 2nd Rev.), IIB-IIIB predominated (66%). Twenty-five patients received intraoperative radiotherapy. Morbidity of re-resection was 28.4%. Residual tumor was detected in 64% of the specimens and clear margins were obtained in 60 patients (90%). With a median follow-up of 57 months the overall local control in patients with tumor-free resection margins was 88% (UICC IA-IIA 100%, IIB-IIIB 82%). Patients treated by adjuvant intraoperative radiotherapy for UICC stages IIB-IIIB with clear margins achieved 90% local control. The 5-year overall survival rate was 87% in patients with tumor-free resection margins. CONCLUSIONS: These findings support the strategy of oncological re-resection after previously non-oncological surgery of STS and imply that re-resection is the prerequisite for any effective adjuvant therapy modality.

Adult↗
PubMed2000

Intraoperative radiotherapy for primary and locally recurrent soft tissue sarcoma: morbidity and long-term prognosis.

INTRODUCTION: Soft tissue sarcoma has a high risk of local recurrence. Therefore, extensive surgical resection has been combined with radiotherapy to improve long-term results. Because external beam radiation doses may be limited by adjacent radiosensitive tissue, intraoperative boost radiation has been devised to achieve a higher total radiation dose in combination with external beam radiotherapy. We report our experience with this multimodal approach for primary and recurrent soft tissue sarcoma. METHODS: Clinical and pathological data were extracted from a prospective data base including all patients with a diagnosis of soft tissue sarcoma treated at the Department of Surgery, University of Heidelberg between 1988 and 1999. Intraoperative radiotherapy dosages were 12-15 Gy for the extremities and 15-18 Gy for the trunk and the retroperitoneum. Additional external beam radiotherapy was given at 40 Gy, whenever possible. RESULTS: Between 1988 and 1999, a total of 251 patients with primary or recurrent soft tissue sarcoma of the extremities, the trunk or the retroperitoneum were treated. The mean (+/- SD) age of 136 men and 115 women was 53+/-16 years. Five of 251 patients died post-operatively, giving a mortality rate of 2.0%. Intraoperative radiotherapy (IORT) was used in 92 patients (37%). Surgical complications were more frequent in IORT patients (30 of 92; 33%) compared to non-IORT patients (36 of 159; 23% P=0.1). Infectious complications were significantly more frequent in patients receiving IORT (P=0.03). Two hundred and four patients were macroscopically tumour-free (R0, R1 resection). For these patients multivariate analysis identified grading (relative risk (RR) 3.1-6.6; P<0.001), age (over 55 years; (RR) 1.8: P<0.008) and tumour location in the retroperitoneum (RR 2.2; P<0.004) as independently associated with recurrence-free survival. The use of IORT (P<0.02) reduced the relative risk of death or recurrence by 40% (RR 0.6; P<0.02). Sex, primary vs. recurrent tumour, T classification and R-status (R0 vs. R1) were not significantly related to recurrence-free survival. CONCLUSIONS: In this prospective, non-randomized study of soft tissue sarcoma IORT was associated with a higher rate of infectious complications, but the the risk of death or recurrence was reduced by 40%.

Adolescent↗
PubMed1998

Detection of SYT-SSX1/2 fusion transcripts by reverse transcriptase-polymerase chain reaction (RT-PCR) is a valuable diagnostic tool in synovial sarcoma.

Cytogenetically, most synovial sarcomas are characterised by a specific chromosomal translocation [(X;18) (p11.2;q11.2)], which results in the generation of fusion transcripts comprising SYT (18q11) and either SSX1 or SSX2 (Xp11) sequences. By using a sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) protocol, specific SYT-SSX1/2 fusion transcripts were detected in 10 histopathologically confirmed synovial sarcomas. Control tumours with morphological spindle cell patterns mimicking monophasic synovial sarcoma tested negative (18/19) in the RT-PCR protocol, with the exception of one spindle cell sarcoma originally classified as a fibrosarcoma. Furthermore, the established RT-PCR protocol was used to evaluate the feasibility of SYT-SSX1/2 fusion transcript detection for minimal residual disease analysis. Analyses of surgical margins revealed a fusion transcript in two of four operations for synovial sarcoma analysed, one of which was diagnosed with tumour free margins by conventional histopathology. These data suggest that the RT-PCR amplification of SYT-SSX1/2 fusion transcripts is a valuable tool in the differentiation of synovial sarcomas, especially in cases of equivocal morphology. Additionally, the RT-PCR approach may be used for the detection of residual tumour cells in synovial sarcoma patients.

Adolescent↗
PubMed1998

[Demonstration of SYT-SSX11/2 fusion transcripts in synovial sarcomas using RT-PCR].

Various mesenchymal malignancies with a spindle cell morphology may mimic monophasic synovial sarcomas. We analysed, whether detection of SYT-SSX1/2 fusion transcripts, present as a consequence of a specific translocation [t(X;18)(p11.2;q11.2)] found in synovial sarcomas, are useful to confirm the diagnosis of synovial sarcoma. A nested RT-PCR protocol was established for the detection of SYT-SSX1/2 fusion transcripts. After RNA extraction of snap frozen tissue reverse transcription was carried out. In a nested PCR, the resulting cDNA samples were amplified and visualized on agarose gels. DNA sequencing of PCR products enabled the assignment of fusion transcripts to either the SYT-SSX1 or the SYT-SSX2 variant. We detected SYT-SSX1/2 fusion transcripts in seven monophasic and three biphasic synovial sarcomas. 20 out of 21 control tumour including leiomyosarcomas, malignant peripheral nerve sheath tumours, gastrointestinal stromal sarcomas and fibrosarcomas were negative in RT-PCR analysis. One case of recurrent spindle cell sarcoma originally classified as a fibrosarcoma revealed a SYT-SSX2 fusion transcript. These data provide further evidence that the RT-PCR amplification of SYT-SSX1/2 fusion transcripts permits the specific identification of synovial sarcomas. This diagnostic approach may be especially useful in cases with equivocal histomorphology.

Chromosome Mapping↗
PubMed1998

[Biologic characterization of soft tissue sarcomes by positron emission tomography (initial results)].

Positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG), carbon-11-labeled aminoisobutyric acid (AIB) and oxygen-15-labeled water (15O-labeled water) was evaluated for imaging soft tissue sarcomas (STS). Eleven pathologically confirmed STS were evaluated by PET using FDG, AIB and 15O-labeled water. All radiotracers showed an increased activity in viable tumor with a significant differentiation from normal tissue (muscle). An increased glucose metabolism in STS allowed a differentiation from normal tissue (muscle) with FDG. Furthermore, STS showed an increased AIB activity suggesting an increased "A-type" aminoacid transport. AIB therefore can be used for evaluation of STS. 15O-labeled water demonstrated an increased uptake with an overlap with blood vessel activity. These radiotracers supply information about biological properties of STS. Five patients with suspicious lesions in conventional radiodiagnostic but negative PET scans were free of local recurrence, diagnosed either by surgery or by follow-up. Two patients with PET findings suggesting local failure, ultimately demonstrated local recurrence. The differentiation of local recurrence from benign postoperative tissue alterations is encouraging and requires further evaluation.

Amino Acid Transport System A↗
PubMed1998

Analysis of FUS-CHOP fusion transcripts in different types of soft tissue liposarcoma and their diagnostic implications.

In myxoid and round cell liposarcomas, a specific chromosomal translocation [(12;16)(q13;p11)] results in the expression of chimeric fusion transcripts encompassing parts of the FUS gene (16p11) at their 5' ends and the CHOP gene (12q13) at their 3' ends. Using a reverse transcription-PCR protocol, we determined the prevalence of FUS-CHOP fusion transcripts in a series of liposarcoma samples. Fusion transcripts were detected in 13 of 30 biopsy samples from soft tissue liposarcomas. Expression of fusion transcripts was not restricted to myxoid and round cell liposarcomas, as suggested previously; it was also detected in 1 of 3 well-differentiated and 4 of 14 pleomorphic liposarcomas. Sequence analysis revealed four different FUS-CHOP fusion transcript variants, two of which have not been described before. Furthermore, using FUS-CHOP fusion transcripts as targets in reverse transcription-PCR assays, we detected disseminated tumor cells in peripheral blood or bone marrow in 3 of 5 patients undergoing surgery for soft tissue liposarcoma.

CCAAT-Enhancer-Binding Proteins↗
PubMed1998

Identical variant TSG101 transcripts in soft tissue sarcomas and various non-neoplastic tissues.

Inactivation of the TSG101 gene was recently shown to induce malignant transformation of NIH/3T3 fibroblasts. Abnormal TSG101 transcription profiles were observed in various human cancers, and large intragenic deletions of the TSG101 gene were reported for a series of human breast cancer specimens, pointing to a potential tumor-suppressive activity of TSG101. However, subsequent more detailed studies on a large panel of breast carcinoma samples did not confirm the tumor-associated genomic deletions. Here we analyzed the transcription patterns of the TSG101 gene in soft-tissue sarcomas and non-neoplastic human tissues. Forty-five of 71 soft tissue sarcoma samples (63%) displayed variant transcripts; however, identical aberrant transcripts were also detected in seven of 15 non-neoplastic control tissues. Restriction fragment length polymorphism analysis of the TSG101 gene excluded major genomic rearrangements in the soft tissue sarcoma samples. Northern blot analysis revealed a very low abundance of variant transcripts as compared with the wild-type TSG101 transcript. These data point to aberrant splicing of the TSG101 mRNA in normal and transformed human mesenchymal tissues rather than tumor specific alterations of the TSG101 gene. In summary, this analyses does not support a pathogenic role for altered TSG101 expression in human soft tissue sarcomas.

Blotting, Northern↗
PubMed1998

[Gastrointestinal stroma tumors--a special entity with unique radicality principles].

Gastrointestinal stromal tumors (GIST) are rare. Their malignant variety represents only 3 percent of all malignant GI tumors. These tumors are most frequently found in the stomach and in the small bowel, while tumors of the large bowel are rare. Notably in the rectum slightly more tumors are found, easy access possibly enhancing diagnosis of asymptomatic lesions. Preoperatively and intraoperatively it is difficult to distinguish benign and malignant lesions. Treatment requires complete removal with a two centimeter margin. Systematic lymphadenectomy is not required. Tumor grading has been determined as prognostic factor for malignant GIST. Overall 5 year survival following potentially curative resection was 69 percent in our series of 46 patients.

Diagnosis, Differential↗
PubMed1998

[Morbidity and tumor control in limb-saving resection with intraoperative radiotherapy in a multimodality therapy concept in soft tissue sarcoma].

This study evaluates limb-saving surgery (LSS) combined with intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) for extremity sarcoma. Prospectively gathered data was analyzed for 50 patients. Advanced stages (UICC IIB-IIIB) predominated (80%) and 50% of the tumors were recurrent. Early local morbidity amounted to 32%, including wound infection (6), skin necrosis (3), hematoma (3) and others (4). Late morbidity of 10% consisted of a fracture, a fibrosis, two chronic lymphedemas and a neuropathy. One patient died (pulmonary embolism). Local control was obtained in 91% with an overall 3-year survival rate of 81% in cases treated with curative intent (follow-up 29 months). No survival benefit was found for patients with microscopically clear margins; however, local failure occurred less frequently (p = 0.02). Our results support the use of LSS with IORT and EBRT for extremity sarcoma and emphasize the importance of the surgical margin.

Adult↗
PubMed1997

[Leiomyosarcoma of the inferior vena cava].

HISTORY AND CLINICAL FINDINGS: In a 34-year-old woman who underwent ultrasound investigation because of recurrent pyelonephritis a space-occupying lesion in the liver was an incidental finding. Computed tomography (CT) and magnetic resonance imaging (MRI) confirmed a tumour in segment I of the liver. The patient had been on contraceptives for 12 years. She had no symptoms. INVESTIGATIONS: Laboratory tests, including tumour markers, were unremarkable. Diagnostic tests to exclude malignant tumour with metastases were negative (thyroid scintigraphy, mammography, coloscopy and gastroscopy). Further tests (ultrasound, coeliaco-mesentericography, hydro-CT and spiral CT, MRI) revealed a tumour, 5 x 4 x 4 cm, in segment I of the liver, most likely an adenoma. Surgical intervention was indicated by the size and questionable malignancy of the tumor. TREATMENT AND COURSE: At operation a tumour was found which originated from the inferior vena cava (IVC) and displaced segment I of the liver. The tumour was resected and the venous wall reconstructed with a Goretex patch. Histological examination indicated a poorly differentiated leiomyosarcoma of the IVC. Adjuvant radiotherapy was undertaken postoperatively. There has been no evidence of recurrence after 10 months. CONCLUSIONS: Leiomyosarcoma of the IVC can be mistaken, both by ultrasound and tomographic diagnostic procedures, for a tumour in segment I of the liver, especially an adenoma. A leiomyosarcoma of the IVC should be included in the differential diagnosis of an hepatic tumour that lies close to segment I of the liver.

Adenoma↗
PubMed1996

[Results of isolated hyperthermic extremity perfusion in soft tissue sarcomas within the scope of a multimodality treatment concept].

Soft-tissue sarcomas (STS) of the extremities are characterized by a high rate of local recurrences. Limb salvage approaches using multimodality therapy protocols have replaced amputation. In order to evaluate isolated hyperthermic limb perfusion (ILP) in a multimodality therapy concept, we reviewed our patients treated using this method. Between January 1982 and December 1995, 25 ILPs, using cisplatin, melphalan and adriamycin, were performed in 22 patients with STS. Forty percent were treated for local recurrences; histology was dominated by malignant fibrous histiocytoma (MFH) and synovial sarcoma. In all, 68% of the STS were classified as UICC stage IIb or IIIa/b. Most of the cases (14) underwent wide or radical resection, 4 patients received intraoperative radiotherapy, and 5 were treated with external beam radiation. Complications were recorded in 32% of the cases. With a median follow-up of 45 months (range 1-143), the 5-year overall survival rate was 81%. The median recurrence-free time was 19 months and the 5-year disease-free survival rate 34%. There were 13 local failures, and distant metastases developed in 36% of the patients. Concerning high-grade sarcomas (UICC stage IIb, IIIa/b), we found local recurrences in 75% of all cases. Five of 11 patients with local failures underwent perfusion after they refused amputation, and 7 incompletely resected STS received ILP without reoperation. All of these demonstrated local recurrence. This rate of local recurrence proved to be different from patients with tumor-free resection margins (p = 0.0001, log-rank test). The amputation rate after isolated limb perfusion was 27% (mean 11 months after treatment). Long-term results of ILP showed a considerable local recurrence rate and a low disease-free survival. Perfusion in patients without tumor-free resection margins does not prevent local recurrence. We conclude that ILP with cisplatin, melphalan and adriamycin should be considered carefully and is not an additional treatment strategy of fist choice.

Adult↗
PubMed1996

[Intraoperative radiotherapy in advanced soft tissue sarcoma of the extremities].

Radical or wide excision is the treatment of choice for soft-tissue sarcomas (STS) of the extremities. Multimodality therapy made limb-sparing surgery possible. While external beam radiotherapy is well established in this setting, few data are available about intraoperative radiotherapy (IORT). We performed an analysis of 36 patients treated with IORT and external beam radiation following resection of STS of the extremities between 1991 and 1995. Only STS classified as UICC stage IIb, III or IV were included. Operative morbidity was 17%, 14% showed late complications. Within a mean follow-up of 24 months (min. 6), there was one local recurrence in 30 patients treated curatively. The 3-year survival rate of patients treated curatively was 75%; 3-year recurrence-free survival was 65%.

Combined Modality Therapy↗
PubMed1995

[Intraoperative radiotherapy within the treatment concept of retroperitoneal soft tissue sarcomas].

Sarcomas of the retroperitoneum are characterized by a high rate of local recurrence. External beam radiotherapy is known to improve local control after surgical therapy. To increase local dosage of radiotherapy without affection of sensitive structures we applied intraoperative radiotherapy (IORT) since 1991 in a dedicated operative unit. To compare morbidity and tumor control we used a partly historic control group of patients treated since 1988 for retroperitoneal soft tissue sarcoma. 25 patients with a mean age of 53 years were operated. Tumor histology was dominated by liposarcoma and leiomyosarcoma, UICC stage IIB (T2 G2 N0 M0) was present in 45% of cases. Distant metastasis were diagnosed in 19% at therapeutic intervention. Tumor free margins were achieved in 55% while 29% showed microscopic and 16% macroscopic tumor residues after surgical intervention. 11 patients received IORT with a mean of 18 Gy, eight of those patients were treated additionally with a mean of 40,4 Gy externally. There were no differences in distribution of known risk factors for recurrence in the group of patients treated with or without IORT. The analysis showed no difference for perioperative morbidity. Tolerance for IORT and additional external beam radiotherapy was good. Local tumor control tended to be improved by IORT (p = 0.082) while overall survival was not affected at a mean follow-up of 24 months.

Adolescent↗