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Biomedical subjects

L Füzesi

Publications and source records attributed to L Füzesi.

At least 37 records · Page 2Linked to original sources
PubMed2002

Surgical cure for early rectal carcinoma and large adenoma: transanal endoscopic microsurgery (using ultrasound or electrosurgery) compared to conventional local and radical resection.

BACKGROUND AND AIMS: The minimally invasive technique of transanal endoscopic microsurgery (TEM) combines the benefits of local resections, a low complication rate and high patient comfort, with low recurrence rate and excellent survival rate after radical surgery (RS). The use of an ultrasonically activated scalpel rather than electrosurgery further improves the results of TEM. PATIENTS AND METHODS: A retrospective study was performed of 182 operations on 162 patients with early rectal carcinoma (pT1, G1/2) or adenoma to compare the outcome following four different kinds of surgical resection techniques: RS (anterior or abdominoperineal resection; n=27), conventional transanal resection using Park's retractor (TP; n=76), transanal endoscopic microsurgery (TEM) with electrosurgery (TEM-ES; n=45), and TEM with UltraCision (TEM-UC; n=34). One-third of the patients with RS (33%) received either a colostomy or a protective loop-ileostomy. RESULTS: Operation time with TEM-UC was significantly shorter than with TEM-ES or RS. Hospitalization was significantly longer with RS than for TEM or TP. Complication rate with TEM was significantly lower than with RS. Recurrence rate with RS and TEM was significantly lower than with TP, with a trend to TEM-UC being better than TEM-ES. Mortality rate was 3.7% with RS and 0 with TP and TEM. The 2-year survival rate was 96.3% with RS and 100% each with TP and TEM. CONCLUSION: TEM using UC seems to be the technique of choice. TP leads to an unacceptable recurrence rate, and RS results in a higher incidence of complication and impairment of life quality.

Adenoma↗
PubMed2002

Deformation-induced endothelin B receptor-mediated smooth muscle cell apoptosis is matrix-dependent.

To maintain normal blood flow, pressure overload in both arteries and veins requires a structural adaptation of the vessel wall (remodelling) that involves smooth muscle cell (SMC) hypertrophy and/or hyperplasia. Due to its potent vasoconstrictor and growth-promoting effects, endothelin-1 (ET-1) is a likely candidate to initiate and/or promote remodelling in blood vessels exposed to a chronic increase in blood pressure. To test this hypothesis, isolated segments of the rabbit carotid artery and jugular vein were perfused at different levels of intraluminal pressure. In both types of segments, pressure overload (160 and 20 mmHg, respectively) resulted in an increase in endothelial prepro-ET-1 and SMC endothelin B receptor (ETB-R) expression. Moreover, in pressurised segments from the carotid artery an ETB-R antagonist-sensitive increase in SMC apoptosis in the media was observed, while in the vein medial SMC started to proliferate. Isolated SMC from these rabbit blood vessels as well as from the aorta and vena cava of the rat, when cultured on a collagen or laminin matrix, uniformly revealed an ETB-R-mediated increase in apoptosis upon exposure to mechanical deformation plus exogenous ET-1 (10 nmol/L). However, when grown on a fibronectin matrix, the cultured SMC did not respond with an increase in apoptosis under otherwise identical experimental conditions. These findings suggest that deformation-induced activation of the endothelin system in the vessel wall not only plays a crucial role in remodelling, but that the structural components of the vessel wall, in particular the cell-matrix interaction, determine how SMC respond phenotypically to these changes in gene expression.

Animals↗
PubMed2002

Transanal endoscopic microsurgery (TEM) for minimally invasive resection of rectal adenomas and "Low-risk" carcinomas (uT1, G1 - 2).

Transanal endoscopic microsurgery (TEM) presents a minimally invasive procedure for local removal of large rectal adenomas (>/= 2 cm) and early, so called "low-risk" carcinomas (uT1, G1 - 2) in curative as well as of advanced tumors in palliative intent. Over a 6-year period 92 TEM excisions of rectal tumors were carried out including 91 patients with 56 adenomas, 35 carcinomas (9 pTis, 17 pT1, 5 pT2, 3 pT3, 1 Ca after snare diathermy) and one neurinoma. Two patients of the carcinoma group had to be reoperated by means of anterior resection due to false preoperative rectal ultrasound examination (2 x uT1--> pT2). 4 patients required palliative therapy on account of age or high morbidity. After a mean follow-up time of 23 months (adenomas 23 months, pT1 carcinoma 26 months and advanced tumors 38 months) we encountered a total of 7 complications, of which in 5 cases surgical reintervention was necessary (5,4 %). One 86-year-old patient with a pT2-carcinoma, who was unsuitable for low anterior resection due to a high morbidity risk, died from myocardial infarction after emergency reintervention caused by postoperative bleeding. To date, overall 9 recurrences occurred (9,8 %). In the specific target group of TEM (adenomas and pT1, G1-2 carcinomas) consisting of n = 83 cases, the overall recurrence rate was 7,2 %, of which 5,3 % were due to adenomas and 11,5 % due to carcinomas. After palliative excision 2 recurrences occurred. These results of transanal endoscopic microsurgery (TEM) indicate that this technique has a useful place in curative, as well as in palliative management of rectal tumors.

Adenoma↗
PubMed2002

Transcription profiling of renal cell carcinoma.

AIMS: Our aim was to prepare a comprehensive catalogue of the changes in gene expression accompanying the development and progression of renal cell carcinoma, and to correlate these with histo-pathological, cytogenetic and clinical findings. METHODS: mRNA samples from paired neoplastic and non-cancerous human kidney tissue were labeled and hybridized in duplicate against high-density cDNA arrays. Two array technologies were used: 31,500-element transcriptome-wide nylon arrays for hybridization with 37 radioactively labelled sample pairs, and 4200-element kidney- and cancer-specific glass microarrays for hybridization with 19 fluorescently labelled sample pairs. RESULTS: We identified more than 1700 cDNA clones that show differential transcription levels in kidney tumor tissue compared to normal kidney tissue. The functional classification of 389 annotated genes provided views of the changes in the activities of specific biological processes in renal cancer. Among the biological processes with a large proportion of up-regulated genes we found cell adhesion, signal transduction, and nucleotide metabolism. Down-regulated processes included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Furthermore, we explored the feasibility of molecular diagnosis for renal cell tumors using cDNA microarrays on glass slides, investigating the association of transcription levels with tumor type, progression, and a putative prognostic variable. The experimental data is available from the GEO gene expression database (http://www.ncbi.nlm.nih.gov/geo; accession no. GSE3), and a comprehensive presentation of the results is available in the web supplement (http://www.dkfz-heidelberg.de/abt0840/whuber/rcc). CONCLUSION: Transcription profiling using high-density cDNA arrays is a powerful method with the potential to improve cancer diagnosis and prognosis. The identification and classification of differentially transcribed genes, as described in our study, is the beginning of a more complete understanding of kidney cancer.

Carcinoma, Renal Cell↗
PubMed2001

Prognostic impacts of cytogenetic findings in clear cell renal cell carcinoma: gain of 5q31-qter predicts a distinct clinical phenotype with favorable prognosis.

To evaluate the prognostic significance of cytogenetic findings in clear cell renal cell carcinoma (RCC), cytogenetic results of 118 primary RCCs were evaluated in relation to classical indicators of prognosis and overall survival. Losses in 3p (98.3%) were most prevalent and included 32 (27.6%) monosomies of chromosome 3 and 84 (72.4%) structural aberrations involving 3p, of which 36 were unbalanced translocations, der(3)t(3;5)(p11-p22;q13-q31), resulting in duplication of 5q sequences. Patients with gain of 5q31-qter resulting from either polysomies or structural rearrangements of 5q, the most frequent of which was der(3)t(3;5), had a significantly better outcome than those without this aberration (P = 0.001). There was no association between gain of 5q or der(3)t(3;5) and any of the well-known variables for prognosis, including low versus high clinical stage and grade of malignancy. Among additional chromosomal aberrations, loss of chromosome 9/9p was associated with distant metastasis at diagnosis (P = 0.006). The data indicate that gain of 5q identifies a clinically favorable cytogenetic variant of clear cell RCC and demonstrate the impact of specific chromosome aberrations as additional prognostic indicators in clear cell RCC.

Adenocarcinoma, Clear Cell↗
PubMed2001

UltraCision or high-frequency knife in transanal endoscopic microsurgery (TEM)? Advantages of a new procedure.

The potential advantages of ultrasound dissection using UltraCision (UC) an ultrasonically activated scalpel, rather than conventional electrosurgery (ES) were investigated retrospectively in 63 patients following transanal endoscopic microsurgery (TEM) in 22 cases of rectal carcinoma (16 pT1, four pT2, two pT3), 40 cases of rectal adenoma >2 cm, and one neurinoma. In all, 21 patients (13 adenomas, seven carcinomas, and one neurinoma) were operated with UltraCision (Ethicon, Norderstedt, Germany), whereas 42 patients (27 adenomas, 15 carcinomas) were treated with conventional electrocautery. All tumors were completely excised (R0) in both groups. We encountered a total of nine complications, seven after ES and two after UC use. Surgical reintervention was necessary in three cases (4.7%), exclusively following resection by ES. There were five cases of tumor recurrence (7.9%), once again only in the ES group. The advantages of ultrasound dissection are magnified under the particular conditions of minimally invasive endoscopic rectum surgery by means of TEM. In principle, all the known risks associated with the application of electric current can be avoided by using ultrasound technology.

Adenoma↗
PubMed2001

A novel management strategy of steroid-free immunosuppression after liver transplantation: efficacy and safety of tacrolimus and mycophenolate mofetil.

BACKGROUND: Corticosteroids have been used traditionally for immunosuppression after solid organ transplantation. The variety of modern immunosuppressive agents offers the chance to replace drugs with an unfavorable risk-benefit ratio. The objective of this prospective pilot study was to investigate a novel steroid-free immunosuppressive regimen after clinical liver transplantation. METHODS: 30 adult liver graft recipients were included in an intent-to-treat analysis. Dual induction immunosuppression consisted of tacrolimus and mycophenolate mofetil. Prophylactic steroids were not given. Efficacy and safety parameters analyzed were patient and graft survival, incidence and severity of rejection, and adverse events in correlation to immunosuppressive drug levels. RESULTS: Patient and graft survival at 2 years was 86.7 and 83.9%, respectively. Acute rejection occurred in 26.2%, and was associated with subtherapeutic tacrolimus blood levels and diarrhea. All rejections were completely reversible by temporary addition of steroids. Acute renal failure was seen in 10/30 patients, and was related to high tacrolimus blood levels together with primary liver graft dysfunction. 43% of all patients never received any steroids, and 73% were on a steroid-free maintenance regimen. CONCLUSIONS: These results confirm that corticosteroids can be completely avoided from the beginning after liver transplantation. Double drug immunosuppression with tacrolimus and mycophenolate mofetil is effective and safe in terms of patient and graft survival as well as incidence and severity of rejection. In order to avoid under- or over-immunosuppression, which may be caused by impaired absorption or metabolism, close drug monitoring is advised.

Acute Disease↗
PubMed2001

Clinical relevance of Fas (APO-1/CD95) expression in laryngeal squamous cell carcinoma.

BACKGROUND: Expression of Fas receptors renders tumor cells potentially susceptible to the host immune system. In squamous cell carcinomas of the head and neck, Fas has recently been found to be down-regulated in some cases; its prognostic value and correlation with clinicopathologic parameters, however, is yet to be delineated. METHODS: Paraffin-embedded specimens of 88 primary laryngeal squamous cell carcinomas were investigated for Fas protein expression by immunohistochemistry. Apoptotic tumor cells were visualized using the nick end labeling method. To assess the immunologic reaction to the neoplasm, the intensity of lymphoplasmocytic stroma reaction was determined. The mean follow-up time amounted to 45.9 months (range, 1-144 months). RESULTS: In tumor-adjacent normal mucosa and in most well-differentiated tumors, Fas expression was restricted to basal and parabasal cell layers. A diffuse pattern of staining reactions predominated in high-grade lesions (p <.001). The degree of Fas expression revealed a positive relationship with the intensity of lymphoplasmocytic stroma reaction (p =.002) but was unrelated to clinicopathologic parameters and to apoptotic rates of tumors. Neither Fas nor the lymphoplasmocytic stroma reaction had any impact on patient survival. CONCLUSIONS: Up-regulation of cell surface Fas expression in laryngeal carcinoma seems to have a stimulatory effect on the immune cell infiltration of the stromal tissue. Its lack of clinical relevance might be due to an inhibition of intracellular Fas signal transduction, which represents a frequent strategy of tumor cells to escape Fas-mediated apoptosis.

Apoptosis↗
PubMed2001

[Endosonography in epithelial rectal tumors. Value of a differentiated therapy concept].

INTRODUCTION: Endorectal ultrasound (EU) is the most important examination for pretherapeutic stratification of primary rectal tumors. Preoperative histology and endosonography determine the therapeutic strategy by using the criteria of depth of infiltration (uT) and lymph node status (uN). METHODS: The effectiveness of endoluminal ultrasound in the preoperative differentiation between locally restricted tumors (adenomas and "low-risk" carcinomas, uT0/1, G1-2) and advanced rectal carcinomas (uT3) was assessed in a retrospective study of 284 patients. In the examination period (UZ) from 3/94 to 12/97 (UZ I) 104 patients (group 1) were examined with a 7-MHz endoprobe, and from 1/98 to 12/99 (UZ II), 116 (group 2) with a 10-MHz endoprobe. Additionally, in 64 patients (group 3) with an advanced uT3/4 or uN + tumor we compared the accuracy of ultrasound with computed tomography (CT). In this group 32 patients were restaged by EU and CT after preoperative chemoradiation. The results of präoperative endorectal ultrasound were correlated with the postoperative histological data. RESULTS: Concerning the whole period (UZ I and II) we achieved a total hit rate of 83.6% for adenomas and "low-risk" carcinomas (uT0/1, G1/2) by EU (79.8% in UZ I, 87.1% in UZ II). For advanced rectal carcinoma (> or = uT3) we found a total accuracy of 87.3% (82.7% in UZ I, 91.4% in UZ II). In 62 cases endosonographic lymph node status was correlated with postoperative histology during UZ II, with a hit rate of 64.5%. In group 3 (n = 64), in 32 patients without preoperative chemoradiation we found an accuracy for depth infiltration of 93% (EU) and 82% (CT). Concerning lymph node status there was a correlation of 57% (EU) and 64% (CT). After preoperative chemoradiation (n = 32) we found an accuracy of 91% (EU) and 73% (CT) for depth infiltration--for lymph node status 70% (EU) and 82% (CT). CONCLUSIONS: High accuracy in endoluminal ultrasound leads to a secure and differentiated stratification of therapy in primary rectal tumors. The hit rate concerning depth of infiltration is higher for EU than for CT both before and after chemoradiation, but not regarding lymph node status.

Adenoma↗
PubMed2001

[Prognostic significance of expression of p53, bcl-2 and bax in squamous epithelial carcinoma of the larynx--a multivariate analysis].

BACKGROUND AND OBJECTIVE: Conventional clinicopathologic parameters do not accurately reflect the clinical outcome of patients with head and neck carcinoma. The establishment of additional prognostic factors that may give insight into the biologic features of a tumor is therefore an essential goal. The present study analyses the expression patterns of p53, bcl-2, and bax with regard to their relationships with conventional tumor parameters and to their prognostic significance in patients with laryngeal squamous cell carcinoma. PATIENTS/METHODS: Paraffin-embedded tissue sections of 88 primary laryngeal squamous cell carcinomas diagnosed and treated between 1986 and 1996 were investigated for p53, bcl-2, and bax protein expression by immunohistochemistry. The mean follow-up time was 45.9 months. RESULTS: Bcl-2 immunoreactivity was positively correlated with an advanced clinical stage, a high T category, regional lymph node metastasis, and a high histological grading. Significant relationship between clinicopathologic parameters and p53 or bax expression were not detectable. The age of the patients, advanced disease, positive bcl-2 expression, and a high level of p53 expression were significantly associated with shortened disease-specific survival in univariate analysis. In multivariate analysis, age, clinical stage, and p53 expression had independent prognostic value. CONCLUSIONS: Although expression of p53 and bcl-2 was found to be clinically relevant in univariate analysis, only p53 but not bcl-2 was an independent predictor of patient outcome. This superiority of p53 in multivariate analysis points to its central role within cell cycle and death regulation, with which it influences two important parameters of tumor progression.

Aged↗
PubMed2001

Clear-cell odontogenic carcinoma with pulmonary metastases resembling pulmonary meningothelial-like nodules.

Clear-cell odontogenic carcinoma (CCOC) is a rare neoplasm with malignant potential and unknown cytogenetic alterations. We describe the case of a 43-year-old woman who presented with an unusual odontogenic epithelial tumor. Histologically, the tumor was composed of clear-cell areas and exhibited a squamous pattern with little nuclear pleomorphism similar to benign squamous odontogenic tumor. Multiple small pulmonary nodules occurring 3 years after primary surgical treatment histologically closely resembled benign minute pulmonary meningothelial-like nodules (MPMN) with clear-cell features. Comparative genomic hybridization (CGH) and immunohistochemistry, performed as diagnostic adjuncts, revealed in the odontogenic tumor and the pulmonary lesions a very similar pattern of chromosomal aberrations (loss of 9, gains of 14q, 19 and 20 in both, and additional loss of 6 in the odontogenic tumor) and the same pattern of expression (positive for cytokeratin 5, 6, 8, 19 and negative for cytokeratin 18, epithelial membrane antigen, and vimentin), differing from that of MPMN. These findings confirmed the final diagnosis of metastasizing CCOC with partial squamous differentiation, substantiated the unfavorable prognosis of the clear-cell component, and highlighted the diagnostic impact of CGH and immunohistochemistry for classification of these morphologically peculiar pulmonary CCOC metastases.

Adenocarcinoma, Clear Cell↗
PubMed2001

Molecular cytogenetic analysis of two primary squamous cell carcinomas of the lung using multicolor fluorescence in situ hybridization.

To fully characterize the numerous chromosomal aberrations in two human squamous cell carcinomas (SCCs) of the lung, molecular cytogenetic characterization was carried out utilizing conventional banding analysis and multicolor fluorescence in situ hybridization (mFISH), providing simultaneous color discrimination of all 24 human chromosomes. Both tumors displayed complex aneuploid karyotypes with a host of numerical and structural chromosome abnormalities. Structural aberrations common to both SCCs included rearrangements of chromosomes 1, 3p, 7q, and 8q, contributing to net loss of chromosomal sequences on 1p, 3p, and 8p, and a net gain of 8q. The recently introduced mFISH technique enabled the disclosure of cryptic translocations and the chromosomal composition of previously unrecognized marker chromosomes. Furthermore, mFISH greatly enhanced the ability to delineate chromosomal breakpoints when integrating banding information from conventional banding analysis. Eventually, the application of mFISH as a powerful approach to refine complex tumor karyotypes is expected to result in a more detailed and complete picture of cytogenetic events associated with the development and progression of solid tumors.

Aneuploidy↗
PubMed2001

Horseshoe lung: report on a new variant--"inverted" horseshoe lung--with embryological reflections on the formal pathogenesis of horseshoe lungs.

The term "horseshoe lung" is used to describe a rare congenital anomaly of the lungs that is characterized by the presence of a midline isthmus of pulmonary parenchyma connecting the posterobasal regions of the right and left lungs. Since the introduction of the term horseshoe lung in the 1960's, almost 40 cases have been reported in the literature. In all these cases, the right and left lungs were joined in their posterobasal regions, the situation resembling that found in horseshoe kidneys. Here we present a case of connection between the right and left lungs found during necropsy of a human fetus. In this case, a midline isthmus of pulmonary parenchyma covered by visceral pleura joined the apical regions of the right and left lungs behind the trachea and esophagus. This connection resulted in a "horseshoe"-shaped lung in which the "horseshoe" was turned by 180 degrees compared to classical cases of horseshoe lung. To the best of our knowledge, this is the first report on an "inverted" horseshoe lung. Embryological reflections on the formal pathogenesis of inverted and classical horseshoe lungs are presented.

Abortion, Spontaneous↗
PubMed2001

mRNA expression of matrix metalloproteases and their inhibitors differs in subtypes of renal cell carcinomas.

Altered expression of matrix metalloproteases (MMPs) and their inhibitors, the tissue inhibitors of matrix metalloproteases (TIMPs), has been demonstrated in various tumour tissues. mRNA expression patterns of MMP-1, MMP-2, MMP-3, MMP-9, MMP-11, MMP-12, MMP-14 and TIMP-1, TIMP-2, TIMP-3 and TIMP-4 were evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in 30 renal cell carcinomas (RCC), as well as in the surrounding tissues. Expression of the MMPs was significantly stronger in the carcinomas than in non-malignant tissues. High levels were demonstrated particularly in clear cell RCCs (CC-RCC). Except for MMP-1, MMP expression in the papillary RCCs (P-RCC) was, for most MMPs, significantly lower. Expression of the TIMPs in malignant cells of both subtypes was weak, with the exception of TIMP-4 which was strongly expressed in the P-RCCs and downregulated in the CC-RCCs. The latter was correlated with chromosomal loss of 3p, harbouring the TIMP-4 gene locus. In conclusion, deregulated expression of the MMPs and TIMPs in RCCs differs according to histology, grade, size and cytogenetic characteristics, suggesting that MMP and TIMP expression patterns play an important role for the typical histomorphological features of RCC subtypes and their respective biological behaviour.

Adenocarcinoma, Clear Cell↗
PubMed2001

[Stereotactic vacuum core biopsy of clustered microcalcifications classified as B1-RADS 3].

PURPOSE: Evaluation of stereotactic vacuum core biopsy of clustered microcalcifications categorized as BI-RADS 3. MATERIAL AND METHODS: 86 patients with microcalcifications BI-RADS 3 (probably benign, < 3% malignant) underwent a stereotactic vacuum core biopsy (Mammotome, Fa. Ethicon Endo-Surgery Breast Care) using a digital stereotactic unit (Mammotest, Fa. Fischer Imaging). The removal of the calcifications was judged by two radiologists in consensus and classified as complete (100%), major (55-99%) or incomplete (< 50%). RESULTS: 4/86 patients could not be evaluated by vacuum core biopsy due to the localization of the microcalcifications close to the skin or lack of detection. In 40/82 cases a complete, in 38/82 a major, and in 4/82 a incomplete removal was achieved. Histology revealed 67 cases of fibrocystic changes, 4 papillomas, 4 fibroadenomas, 4 cases of atypical ductal hyperplasia (ADH), and 3 ductal carcinomas in situ (DCIS), one of these with a minimal-invasive tumor component. Patient with ADH were advised to undergo surgical biopsy. Histology revealed complete removal. 7 patients had complications or side-effects. CONCLUSIONS: Percutaneous vacuum core biopsy is a reliable minimal-invasive diagnostic method to come to the final diagnosis in patients with clustered microcalcifications categorized BI-RADS 3. However, if malignancy is proven (about 4% of our cases) an open biopsy is necessary.

Adult↗
PubMed2001

Identification and classification of differentially expressed genes in renal cell carcinoma by expression profiling on a global human 31,500-element cDNA array.

We investigated the changes in gene expression accompanying the development and progression of kidney cancer by use of 31,500-element complementary DNA arrays. We measured expression profiles for paired neoplastic and noncancerous renal epithelium samples from 37 individuals. Using an experimental design optimized for factoring out technological and biological noise, and an adapted statistical test, we found 1738 differentially expressed cDNAs with an expected number of six false positives. Functional annotation of these genes provided views of the changes in the activities of specific biological pathways in renal cancer. Cell adhesion, signal transduction, and nucleotide metabolism were among the biological processes with a large proportion of genes overexpressed in renal cell carcinoma. Down-regulated pathways in the kidney tumor cells included small molecule transport, ion homeostasis, and oxygen and radical metabolism. Our expression profiling data uncovered gene expression changes shared with other epithelial tumors, as well as a unique signature for renal cell carcinoma. [Expression data for the differentially expressed cDNAs are available as a Web supplement at http://www.dkfz-heidelberg.de/abt0840/whuber/rcc.]

Carcinoma, Renal Cell↗