Search PubMed⌕ Search

Biomedical subjects

M Stas

Publications and source records attributed to M Stas.

At least 19 recordsLinked to original sources
PubMed2002

18-FDG PET scan in the staging of recurrent melanoma: additional value and therapeutic impact.

Staging of melanoma patients by means of whole body functional imaging in a single evaluation session using positron emission tomography (PET) with fluorine-18- labelled deoxy-d-glucose (FDG) as a metabolic tracer has created much interest over the last decade. After enthusiastic pilot studies, more attention has been paid to the false-negative and false-positive results of this technique than to its true therapeutic impact. This study aimed to evaluate (1) the sensitivity and specificity of this technique at a single lesion level compared with conventional screening procedures (CSP) - both of these accompanied by careful clinical examination; and (2) the additional value of the PET scan at the level of the individual patient and its therapeutic impact for different types of melanoma recurrence. A consecutive series of 100 PET scans performed on 84 melanoma patients with regional or distant recurrence according to CSP (89 PET scans) or suspicion of recurrence, i.e. inconclusive CSP (11 PET scans), were retrospectively analysed and compared with the CSP results. At the single lesion level, PET scan and CSP showed a sensitivity of 85 and 81%, a specificity of 90 and 87% and an accuracy of 88 and 84%, respectively. PET provided false-negative results for small skin metastases and brain involvement; false-positive results were associated with unrelated benign or malignant tumours and peripheral soft tissue and bone uptake. PET scan showed an additional value over and above CSP at the individual patient's level by true upstaging in 10 cases, true downstaging in 24 cases and depiction of more lesions within the same stage of disease in 15 cases. The overall therapeutic impact reached 26%: 17 out of 71 (24%) cases with regional recurrence, one out of 18 cases (5.5%) with distant metastasis and eight out of 11 cases (73%) with suspicion of recurrence where CSP remained doubtful. However, in 19 cases comparison between CSP and PET resulted in discordant findings, suggesting upstaging in one area and downstaging at another site within the same patient. In conclusion, PET scan has an additional value in the staging of recurrent melanoma, providing it is accompanied by careful clinical examination and specific brain imaging. However, in the absence of evidence of metastasis or unrelated conditions at the same site on CSP, PET spots may represent false-positive images, which would falsely upgrade a patient to an incurable state, or they may be early true-positive findings, which will become evident during close follow-up.

Adult↗
PubMed2001

Sleeve-related thrombosis: a new form of catheter-related thrombosis.

In a detailed study of central venous catheter-related sleeve and thrombosis in experimental animals, a new form of thrombosis was detected and termed sleeve-related thrombosis. A silastic catheter was placed in the jugular vein and the anterior vena cava of 22 rabbits and 54 rats. After intervals of 1, 3, 7 days, 2, 3, 4 weeks and 1, 2, 4, 6 months the veins were examined by light microscopy and by transmission electron microscopy. In about 50% of the rats a thrombus was observed at the end of the catheter sleeve. Consecutive cutting allowed the visualization of a transition from a sleeve via part of sleeve and part of thrombus to a pure thrombus. This thrombus was separated from the vein wall and could not be considered a mural thrombus. As the thrombus was only attached to the terminal part of the organized catheter sleeve we propose the name sleeve-related thrombosis.

Animals↗
PubMed2001

A novel N-ras mutation in malignant melanoma is associated with excellent prognosis.

Mutations in the ras gene are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in malignant melanoma (MM). We searched for point mutations in the N-ras gene in a large series of primary and metastatic MM from 81 different retrospectively selected patients using the very sensitive denaturing gradient gel electrophoresis technique, followed by sequencing. The classical codon 12 and codon 61 mutations were found in 21 and 17% of the cases, respectively. No codon 13 mutation was found. A novel mutation at codon 18 of exon 1, consisting of a substitution of alanine (GCA) by threonine (ACA), was found in 15% of the primary MMs but in none of the metastatic MMs. All of the other cases were free of mutations. Using microdissected cells from distinctive MM growth phases as source of DNA for mutation analysis, this particular N-ras exon 1 mutation at codon 18 was already present in the radial growth phase and preserved throughout the successive growth phases; it was also found in a dysplastic nevi in continuity with a MM, indicating a clonal relationship between both lesions. Our findings also illustrate the clonal relationship between the distinctive growth phases in MM and suggest the codon 18 mutation to occur early in MM development. The MM in patients with this mutation were significantly thinner than those without a codon 18 mutation (P = 0.0257). Statistical analysis, comparing the group of codon 18 patients with the group of patients with the classical mutations and without mutations, revealed a highly significant difference in overall outcome. The cumulative probability of developing metastasis was significantly lower for the group patients with a codon 18 mutation (P = 0.0130). We can thus conclude that this codon 18 mutation identifies a group of patients with better prognosis than patients with melanoma that harbor wild-type sequence or classical activating point mutations in codon 12 or 61. Preliminary nucleotide binding measurements could not detect a difference between wild-type Ras protein and the mutant Ras(A18T) protein. However, for a precise elucidation of the role of the N-Ras(A18T) mutant in melanoma, additional studies aimed to measure the affinity to guanine nucleotide exchange factors and GTPase-activating proteins are needed.

Codon↗
PubMed2001

Expression of the endothelin-B receptor in pigment cell lesions of the skin. Evidence for its role as tumor progression marker in malignant melanoma.

Endothelins (ETs) exert several functions in human melanocytes, including proliferation, dendrite formation, and melanin synthesis. Among the ET receptors, the non-selective endothelin-B (ETB) receptor is the major receptor in melanocytes and malignant melanoma (MM) cells. In spite of the important role of ETs and their receptors in the growth and differentiation of melanocytes, the distribution and expression levels of ETB receptors in tissue sections of benign and malignant pigment cell lesions is still unknown. We combined immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to study ETB receptor expression in benign and malignant pigment cell lesions and in normal skin. Immunohistochemistry on paraffin-embedded tissue sections of 159 cases revealed a significant increase in intensity of ETB receptor expression from common nevi over dysplastic nevi and primary MM to metastatic MM. Quantitative PCR using realtime detection on 75 samples confirmed the immunohistochemical results. These data add the ETB receptor to the growing list of tumor progression markers in MM and suggest that ETs play a role in the progression of MM in the skin.

Biomarkers, Tumor↗
PubMed2001

Analysis of N- and K-ras mutations in the distinctive tumor progression phases of melanoma.

Mutations in the ras genes are key events in the process of carcinogenesis; in particular, point mutations in codon 61 of exon 2 of the N-ras gene occur frequently in cutaneous melanoma. To investigate whether these mutations occur in early or late tumor progression phases, we searched for point mutations in the N- and K-ras genes in 69 primary cutaneous melanoma, 35 metastases, and seven nevocellular nevi in association with cutaneous melanoma. Lesions were microdissected in order to procure pure tumor samples from the distinctive growth phases of the cutaneous melanoma; the very sensitive denaturing gradient gel electrophoresis technique was used to visualize the mutations, and was followed by sequencing. Point mutations in the N-ras gene but not in the K-ras gene were detected on denaturing gradient gel electrophoresis. Twenty-three primary (33%) and nine metastatic (26%) melanomas showed bandshifts for N-ras. In the majority of cases, mutations occurring in early growth phases (i.e., the "intraepidermal" radial growth phase), were preserved in later growth phases (i.e., the invasive radial growth phase, vertical growth phase, and metastatic phase), which proves the clonal relationship between the successive growth phases. In three cases, however, the mutations differed between the distinctive growth phases within the same cutaneous melanoma, due to the occurrence of an additional mutation (especially in codon 61) in a later tumor progression phase. Our approach also permitted us to analyze the mutational status of nevi, associated with cutaneous melanoma. Six out of seven associated nevi carried the same sequence (mutated or wild-type) as the primary cutaneous melanoma, whereas in one case the sequence for N-ras differed between the primary melanoma and the associated nevus. In conclusion, this approach allowed us to demonstrate the clonal relationship between subsequent growth phases of melanoma and associated nevi; our results suggest that N-ras exon 1 mutations preferentially occur during early stages of tumor progression and hence may be involved in melanoma initiation, whereas those in N-ras exon 2 are found preferentially during later stages and hence are more probably involved in metastatic spread of cutaneous melanoma.

Disease Progression↗
PubMed2000

Minimal deviation and/or naevoid melanoma: is recognition worthwhile? A clinicopathological study of nine cases.

One to two per cent of primary cutaneous melanomas share clinical features with benign melanocytic and non-melanocytic skin lesions, and even at histology recognition of their malignant nature is problematic, mainly due to the lack of an intraepithelial component, their nodular aspect and the monotonous cell population throughout the lesion. These tumours were termed minimal deviation melanomas (MDMs) by Reed et al. and later naevoid melanomas by Schmoeckel et al. The name MDM suggests the concept of a more favourable outcome for these melanomas that do not (yet) show the typical features of fully evolved lesions able to metastasize, although naevoid melanomas seem to behave like 'common' melanomas. In a retrospective analysis of nine cases of MDM collected from our database and followed for a median duration of 112 months, we faced similar clinical and histological pitfalls and observed local recurrence following marginal resection. Wide excision, even of local recurrence, and therapeutic node dissection could nevertheless provide survival comparable at least to that predicted by mathematical models for patients who initially had optimal treatment.

Adult↗
PubMed2000

Intimal hyperplasia after long-term venous catheterization.

OBJECTIVE: Intimal hyperplasia is a well-known consequence of arterial injury and arterialization in vein grafts. However, the subacute and chronic vein wall changes which occur after catheterization have not been well studied. In this animal study, intimal hyperplasia in the vein wall after catheterization was examined. METHODS: A silicon catheter was placed in the anterior caval vein of 54 rats. After in situ fixation at scheduled intervals (1 day to 6 months), the pathologic changes in the vein wall were studied on semi-serial histology sections by means of light microscopy. RESULTS: Three forms of intimal hyperplasia could be observed: plaque-like, papillary-like and incorporation of the mural part of the sleeve into the underlying vein wall. Although the appearance of each was different, their composition was identical. All were mainly composed of alpha-actin-positive cells and collagen localized above the internal elastin layer, and covered by endothelium if facing the lumen. The plaque-like and papillary-like forms were mainly localized in the anterior vena cava, while sleeve incorporation mainly occurred in the jugular vein. Plaque-like and papillary-like intimal hyperplasia could be seen together on the same slide, but these two forms were never seen together with sleeve incorporation. CONCLUSION: Intimal hyperplasia occurs after venous catheterization and is probably caused by chronic injury to the vein wall due to knocking and rubbing movements of the catheter against the wall.

Actins↗
PubMed1999

Proliferative myositis in a child.

A case of proliferative myositis in the lumbar paraspinal muscles in a 14-year-old boy is presented. Imaging investigations including plain radiograph, ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), bone scan and positron emission tomography (PET) were suggestive of an inflammatory process such as myositis ossificans. The diagnosis was made by incisional biopsy. More pronounced edema, more muscle fiber necrosis and a higher cellularity were found compared to adult cases. The karyotype of the lesion was normal. Clinically, the mass disappeared spontaneously. After 24 months, asymptomatic bridging ossification between the third and fourth lumbar vertebrae was noted.

Adolescent↗
PubMed1998

Translocation (X;1) reveals metastasis 31 years after renal cell carcinoma.

Cytogenetic investigation of a metastatic lesion appearing 31 years after nephrectomy allowed for the diagnosis of a renal cell carcinoma. The der(X)t(X;1)(p11.2;q21.1) found in this case and review of the 14 other cases previously reported indicates that this chromosome lesion may characterize a specific subgroup of renal cell carcinoma, with distinct histology and age distribution that also can occur in females.

Carcinoma, Renal Cell↗
PubMed1998

Composition and formation of the sleeve enveloping a central venous catheter.

PURPOSE: After catheterization, 42% to 100% of central venous catheters are surrounded by a "fibrin sleeve." This sleeve has been considered the cause of catheter-related infections, withdrawal occlusion, and pulmonary embolism. The reactions between the vein wall and the catheter were studied. METHODS: A silicone catheter was placed in the anterior caval vein of 123 rats. After in situ fixation at scheduled intervals, the pathologic changes were studied on semi-serial histologic sections by means of light microscopy, transmission electron microscopy, and scanning electron microscopy (SEM). In 36 rats, the catheter was withdrawn immediately; in 72 rats, it was left in situ up to 6 months; and in 15 rats, the study was performed up to 10 months after withdrawal of a catheter that had remained in situ for 6 months. RESULTS: In the group in which the catheter was withdrawn immediately, mural thrombi disappeared by day 7. In the group in which the catheter remained in situ, thrombi remained around the proximal portion of the catheter. This pericatheter thrombosis (PCT) was invaded by migrating and proliferating smooth muscle cells (SMCs), originating from an injured vein wall, and transformed from day 7 into a tissue composed predominantly of SMCs and collagen and covered by endothelial cells. Later, the number of cells decreased, and the relative amount of collagen increased. Up to 10 months after withdrawal of the catheter, the collapsed sleeve was still present within the vein. CONCLUSION: The sleeve around a central venous catheter is not a fibrin sleeve, but a stable cellular-collagen tissue covered by endothelium. It is mainly formed by smooth muscle cells migrating from the injured vein wall into the early pericatheter thrombus.

Animals↗
PubMed1997

Lesions of 13q may occur independently of deletion of 16q in spindle cell/pleomorphic lipomas.

AIMS: Very recent multidisciplinary investigations have allowed for the definition among lipomas of a clinical and histological subtype called spindle cell and/or pleomorphic lipoma, possibly associated with partial monosomy 16 and anomalies of chromosome 13. In order to get nearer to the underlying critical molecular changes further multidisciplinary pathological and genetic research is indicated, to identify which chromosome(s) anomalies are crucial in the development of these tumours. METHODS AND RESULTS: In an ongoing multidisciplinary study of lipomatous tumours, including clinical findings, morphology, histochemistry and cytogenetics, two instances were found of spindle cell lipoma with clonal chromosome changes. In both cases chromosome 13 was involved, whereas only one showed a partial monosomy 16. CONCLUSIONS: Partial monosomy 16 is a characteristic lesion in spindle cell lipoma, usually associated with anomalies of chromosome 13. The present report confirming a previous single observation indicates, however, that lesions of 13 may occur independently from lesions of 16, suggesting different underlying molecular lesions in these otherwise very similar lipomas.

Chromosome Deletion↗
PubMed1997

Neuromuscular choristoma (hamartoma) with smooth and striated muscle component: case report with immunohistochemical and ultrastructural analysis.

Benign peripheral nerve tumors with a mesenchymal component are rare and are represented principally by the neuromuscular choristoma. We describe an 11-month-old male infant who presented with a mass arising from the left brachial plexus. The lesion was bound firmly to the involved nerves and consisted histologically and ultrastructurally of bundles of well-differentiated smooth muscle cells intermingled with striated muscle fibers and unmyelinated nerve fibers. In the 13 previously published cases of neuromuscular choristoma, no smooth muscle component was observed. This unique peripheral nerve choristoma with not only striated but also smooth muscle closely resembled neuromuscular choristoma and was considered a variant of it.

Brachial Plexus↗
PubMed1997

Prognostic significance of nm23 protein expression in malignant melanoma. An immunohistochemical study.

The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A and B, have been found to serve as metastasis-suppressor genes in experimental animal models of tumour progression, and in some, but not all cancers in man. To investigate the role of NM23 in the progression of human malignant melanoma, we studied the expression and distribution of the nm23 protein with a sensitive immunohistochemical technique and a well-characterized monoclonal antibody in 41 benign pigment cell lesions and 71 uniformly treated malignant melanomas with a long follow up-up. In benign naevi, the junctional nests frequently expressed nm23 protein, whereas the immunoreactivity tended to decrease when the lesions matured. All malignant melanomas expressed nm23 protein in their vertical and/or radial growth phases, and the immunoreactivity tended to increase towards the deeper parts of the lesion. No relation was found between nm23 expression and patient outcome. In addition, nm23 was found in activated lymphoid cells, and this feature was significantly associated with a brisk lymphocytic stroma response in malignant melanomas. Our data are at variance with previous mRNA studies on malignant melanoma, and indicate that routine immunohistochemical analysis for nm23 protein on paraffin-embedded tumour tissue cannot reliably be used as a prognostic marker for patients suffering from malignant melanoma. In contrast, our findings suggest that the nm23 protein in pigment cell lesions is related to the proliferative or activated state of pigment cells, rather than to their metastatic potential.

Adult↗
PubMed1996

Temporary colostomy in supralevator pelvic exenteration. A comparative study between stapled loop and loop colostomy.

A temporary loop colostomy is created in most patients undergoing total supralevator pelvic exenteration with low rectal anastomosis. We report 16 patients comparing two different types of loop colostomy. In half of them a normal loop colostomy was made and refashioning of the stoma was necessary in two patients because of faecal spillover in the presence of anastomotic leakage. In the other eight patients a functional terminal colostomy was created by application of a TA 55 stapler on the efferent loop. In this group no refashioning of the stoma was necessary and no difficulties were encountered on closure of this type of colostomy. Because of the high incidence of anastomotic leakage in this population, the stapled loop colostomy is the preferred method of choice because it eliminates any possible faecal spillover.

Adult↗
PubMed1996

CD40 is a prognostic marker in primary cutaneous malignant melanoma.

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.

Biomarkers, Tumor↗
PubMed1994

Some desmoid tumors are characterized by trisomy 8.

Ten desmoid tumors were examined by chromosome banding analysis and by in situ hybridization on short-term cultures and frozen sections. Trisomy 8 was detected in four out of ten tumors, of which only one had shown trisomy 8 by karyotype analysis. Since trisomy 8 has been reported in superficial fibromatoses, which are clinically distinct but histologically similar to desmoid tumors, the occurrence of trisomy 8 in both may be a further indication of a close relationship.

Adolescent↗