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L Füzesi

Publications and source records attributed to L Füzesi.

At least 19 recordsLinked to original sources

An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications.

To model the cytogenetic evolution in gastrointestinal stromal tumour (GIST), an oncogenetic tree model was reconstructed using comparative genomic hybridization data from 203 primary GISTs (116 gastric and 87 intestinal GISTs, including 151 newly analysed cases), with follow-up available in 173 cases (mean 40 months; maximum 133 months). The oncogenetic tree model identified three major cytogenetic pathways: one initiated by -14q, one by -1p, and another by -22q. The -14q pathway mainly characterized gastric tumours with predominantly stable karyotypes and more favourable clinical course. On the other hand, the -1p pathway was more characteristic of intestinal GISTs, with an increased capacity for cytogenetic complexity and more aggressive clinical course. Loss of 22q, more closely associated with -1p than -14q, appeared to initiate the critical transition to an unfavourable cytogenetic subpathway. This -22q pathway included accumulation of +8q, -9p, and -9q, which could all predict disease-free survival in addition to tumour site. Thus, insights into the cytogenetic evolution obtained from oncogenetic tree models may eventually help to gain a better understanding of the heterogeneous site-dependent biological behaviour of GISTs.

Chromosome Aberrations↗

Histomorphological tumor regression grading of esophageal carcinoma after neoadjuvant radiochemotherapy: which score to use?

Histopathological tumor regression grade (TRG) has been shown to be a prognostic factor in patients with esophageal cancer after neoadjuvant radiochemotherapy (RCT). The system introduced by Mandard to group TRG (Cancer 1994;73:2680-2686) has been used to analyse and discuss its prognostic significance on survival in a single institution retrospective analysis: TRG 1 (complete regression) - TRG 5 (absence of regressive changes). Sixty patients with locally advanced (T3/4 or N1) adenocarcinoma or squamous cell carcinoma received cisplatin-based RCT. Three to four weeks later operation for curative intent was performed. Median follow-up was 17.7 months. Histopathological tumor stages were stage 0 in 17%, stage I in 10%, stage II in 60%, stage III in 12% and stage IVA in 1%. The 5-year overall survival (OS) rate was 35%. In univariate analysis, ypN-status and TRG correlated significantly with OS (P = 0.004, P = 0.0008, respectively). While OS of TRG 1 differed significantly from all other groups, no differences in OS between the other TRG groups were seen. Patients with complete tumor regression after neoadjuvant RCT showed a much better survival than patients with tumors that responded less to induction therapy. Further qualitative subdivision of tumor regression could not identify patient groups with significant differences in prognosis. After comparing our data with the literature, it is reasonable to consider classifying all patients into 'Complete tumor regression' and 'Incomplete tumor regression'.

Esophageal Neoplasms↗

Parvovirus B19 detected in Rosai-Dorfman disease in nodal and extranodal manifestations.

Sinus histiocytosis with massive lymphadenopathy (SHML), also designated as Rosai-Dorfman disease (RDD), is a rare benign reactive lymphoproliferative disorder. It is defined by a characteristic histopathology with sinus histiocytosis and haemophagocytosis known as emperipolesis. In histiocytes S100 is strongly expressed, whereas CD1a staining typically is negative. The disease mainly manifests at a single lymph node; however, multilocular and extranodal affection can occur. Causative infectious agents, and virus infections in particular, have repeatedly been suspected, although until now the origin of the disease has been unclear. Four cases of RDD (two nodal sites and two extranodal upper respiratory tract sites) were analysed for parvovirus B19 (B19) infection by immunohistochemistry to detect B19 capsid proteins VP1/VP2. In all the four cases, huge numbers of B19-positive cells were partly detected. The positive cells were identified either as lymphocytes or, in one extranodal case, also as respiratory epithelial cells. This is the first report of B19 infection in RDD tissue, indicating that B19 may be associated with the pathogenesis of SHML.

Adult↗

Simultaneous tumour-like, atypical basal cell hyperplasia and acinar adenocarcinoma of the prostate: a comparative morphological and genetic approach.

Basal cell tumours of the prostatic gland are rare, and the classification is difficult. In the present case report, a large, tumour-like proliferation of atypical basaloid cells was found incidentally in a prostatectomy specimen that otherwise contained a conventional acinar adenocarcinoma. The basaloid cells displayed a solid or adenoid-cystic growth pattern and strongly expressed high-molecular-weight cytokeratins and bcl-2. A high Ki-67 index was recorded within the atypical basaloid cells, by far exceeding the one counted in the conventional adenocarcinoma. However, there were no definite criteria for a malignant behaviour of the basal cell tumour. Comparative genomic hybridisation from microdissected tumour cells yielded losses at the short arms of chromosomes 8 and 12 in the conventional adenocarcinoma and a normal karyotype in the basal cell tumour. The pathological findings favoured the diagnosis of an atypical basal cell hyperplasia.

Carcinoma, Acinar Cell↗

[In-vitro study of the cellular response of human fibroblasts cultured on alloplastic hernia meshes. Influence of mesh material and structure].

BACKGROUND: The biocompatibility of meshes in hernia surgery seems to be influenced markedly by the amount of the selected material and its structure. Fibroblasts play a major key role during the process of mesh incorporation. This study was performed to investigate differences in cell morphology and proliferation of human fibroblasts cultured on different polypropylene meshes. METHODS: In the present in vitro study the cellular response of human fibroblasts was investigated by scanning electron microscopy (SEM), comparing three different polypropylene meshes: a newly constructed low-weight and microporous mesh (NK1), a low-weight and macroporous mesh with absorbable polyglactin filaments (Vypro), and a heavy-weight and microporous mesh (BiomeshP1). Human fibroblasts (1,5.10(5) cells) were incubated with the meshes (each 12 mm(2)) for 6 hours, 5 days, 2, 4, 6, and 12 weeks. Computer-assisted morphometry of the fibroblast/mesh surface ratio served to reflect the biological cell response. RESULTS: The Vypro mesh showed the significantly highest fibroblast density during the first 6 weeks, but cell growth was nearly exclusively limited to the polyglactin filaments. At 3 months, after reabsorption of the polyglactin, the fibroblast-coated polypropylene mesh surface was only 50% compared to NK1 and BiomeshP1. The morphologic aspect of the fibroblasts on the BiomeshP1 mesh was much more degenerative and unphysiological, compared to NK1 and Vypro, with isolated, single cells instead of a broad, connective growth. The BiomeshP1 showed a significantly higher fibroblast proliferation around the nodes of the mesh compared to the straight filaments. On the NK1 mesh fibroblasts exclusively proliferated on the filaments but not on the pressed mesh surface. CONCLUSIONS: The polymer surface and structure appears to be of major importance for the biocompatibility of meshes: human fibroblasts preferably grow on low-weight meshes, thin filaments, and mesh nodes. Heavy-weight meshes induce degenerative cell reactions. Polyglactin seems to further improve cell proliferation whereas a pressed mesh surface without pores hinders fibroblast growth.

Cell Count↗

[Significance of occult lymphatic tumor spread in pancreatic cancer].

PURPOSE: The aim of this study was to determine the frequency and effect on prognosis of occult tumor cells in regional lymph nodes judged to be tumor-free in conventional histopathology of pancreatic cancer patients. PATIENTS AND METHODS: Among 115 patients who underwent pancreatic resection for pancreatic (n=84) or distal common bile duct malignancy (n=12) or carcinoma of the papilla (n=19), 48 (42%) were staged pN0. Archival paraffin blocks of 271 resected regional lymph nodes of 41 pN0 patients were reevaluated for occult tumor cells using monoclonal antibody Ber-EP4. Cases with or without isolated tumor cells were compared regarding the distribution of various clinicopathological factors. RESULTS: Of 41 pN0 patients, 16 (39%) exhibited single Ber-Ep4 immunoreactive cells or small cell clusters in at least one lymph node. The occurrence of occult tumor cells was not dependent on other clinicopathological factors such as pT stage, grading, or curative resection. However, those cells were encountered more frequently in common bile duct carcinomas (100%) than in pancreatic (36%) or papilla (20%) carcinomas (P=0.009). Occult tumor cells impaired prognosis significantly in uni- and multivariate analyses (estimated 5-year survival 53% for pN0((i-)) vs 10% for pN0((i+)) and 9% for pN1/N2; P=0.0047). CONCLUSION: Occult tumor cells are frequent in apparently tumor-free lymph nodes of pancreatic cancer patients and often overlooked in conventional histopathology. They are encountered even in limited stages of disease and they impair prognosis, which is comparable to that of patients with true lymphatic metastases. Occult tumor cells in lymph nodes of pancreatic cancer patients could be used to stratify adjuvant therapy.

Aged↗

Gastrointestinal stromal tumor (GIST) -- single center experience of prolonged treatment with imatinib.

BACKGROUND: The tyrosine kinase inhibitor imatinib has been introduced into the treatment of gastrointestinal stromal tumors (GIST). Here we report our results of prolonged treatment in comparison to a similar group of GIST patients who had died before imatinib became available. METHODS: Fourteen patients with recurrent or metastatic GIST were treated with imatinib. Clinical data and tumor samples of ten patients from the pre-imatinib era were available for comparison. Comparative genomic hybridisation (CGH) was performed on tumors to identify changes that may predict response to treatment. RESULTS: Fourteen patients were treated, mean treatment time 22.3 months (1 non-response, 2 progression after initial response, 2 stable diseases, 8 partial responses, 1 complete response). Adverse side effects were mild in general. Survival was higher in the treated group (41.1 months vs. 34.8 months in the historical group). Eleven treated patients are alive. CGH analysis showed comparable numbers of chromosomal aberations in both groups. CONCLUSION: Prolonged treatment with imatinib is safe and effective in patients with recurrent or metastatic GIST.

Adult↗

Expression of the sodium iodide symporter in differentiated thyroid cancer: clinical evidence.

AIM: Molecular analysis of the expression of the sodium iodide symporter (NIS) in 32 patients with differentiated thyroid cancer (DTC) and correlation with scintigraphic findings ((131)I,(123)I) in 19 (59.4%) of them. PATIENTS, METHODS: NIS expression of 27 primary tumours, 13 lymphnodes and 18 distant metastases was determined by immunostaining using a murine monoclonal anti-NIS-antibody. NIS expression and radionuclide uptake of metastases were analysed by a semiquantitative visual score. Patients were divided into two subgroups: Group 1 (n = 8 patients): indirect correlation of radioiodine uptake (RIU) of subsequent metastases with NIS expression of 7 primary tumours and 3 metastases; Group 2 (n=11 patients): direct correlation of radionuclide uptake with NIS expression of 19 metastases which were excised after imaging. RESULTS: 49 of 58 specimens (84.5%) were NIS-positive. A preserved NIS-expression was found in 12 primary tumours and 8 of 10 (80%) synchrone and 6 of 7 (85.7%) metachrone metastases. Group 1 revealed a 100% positive predictive value (PPV) of a preserved NIS expression in the primary tumour regarding radioiodine uptake in metastases while a lack of NIS expression in the primary tumor did not reliable predict a loss of the metastases' ability to concentrate radioiodine. In group 2, only 11 of 19 (57.9%) specimens showed a concordant NIS expression and RIU whereas in the remaining 8 cases without visible RIU NIS expression was still present. CONCLUSIONS: NIS expression of the primary tumour and metastases in DTC is usually well preserved. We found a positive correlation between NIS expression of the primary and metastatic tissue but could not identify such well correspondence between NIS expression and the RIU of subsequent metastases.

Adult↗

Prognosis factors in incisional hernia surgery: 25 years of experience.

BACKGROUND: Incisional hernia underwent a change from conventional techniques to mesh implantation. The relevance of different factors, like operative technique, mesh material, and patient-related parameters concerning the outcome following mesh repair, are still under debate. METHODS: In a comparative retrospective study of 421 incisional hernia operations on 348 patients, we investigated 241 Mayo procedures and 180 mesh repairs over a 25-year period. In addition to the quality of life following mesh implantation, the prognostic relevance of demographic, preoperative and intraoperative parameters, surgical technique, mesh material, and the surgeon's experience were analysed, both in a univariate and multivariate manner. RESULTS: With a mean follow-up of 9.7+/-8.8 years, the total recurrence rate following Mayo overlap was 37%, in contrast to 15% after mesh implantation (P=0.001). Mesh size was the only significant prognostic factor concerning quality of life following mesh implantation, and 86% of the patients with mesh repair were satisfied. The complication rate was determined significantly by patients' risk factors, size of hernia, operative technique, and the surgeon's experience, whereas the rate of recurrences was significantly influenced by the parameters obesity (BMI>25), size of hernia, and surgical experience. The recurrence rate decreased significantly with surgeon's experience-a minimum of 16 mesh repairs led to a recurrence rate of less than 10%. CONCLUSIONS: Only the mesh repair revealed acceptable recurrence rates with high patient comfort. From a surgical point of view, the most important prognostic factor following mesh repair is the surgeon's experience.

Female↗

Impact of vasoactive intestinal polypeptide and gastrin-releasing peptide on small bowel microcirculation and mucosal injury after hepatic ischemia/reperfusion in rats.

BACKGROUND AND AIMS: Alterations in microvascular perfusion of the intestine after hepatic ischemia/reperfusion have been suggested as an important cause of postoperative septic complications. We therefore investigated small bowel microcirculation and mucosal injury after liver ischemia/reperfusion in a rat model. Furthermore, we analyzed the effects of the regulatory peptides vasoactive intestinal polypeptide and gastrin-releasing peptide for their splanchnic vasoactivity. METHODS: Hepatic ischemia was induced by clamping of the left hepatic artery and vein for 40 min, followed by 60 min of reperfusion. The control group was treated similarly, but without clamping of the liver vessels. Ten minutes after clamping of the hepatic vessels, vasoactive intestinal polypeptide or gastrin-releasing peptide, respectively, were continuously infused intravenously in the experimental groups. Small bowel microcirculation and mucosal injury were assessed using intravital microscopy and the Chiu-score, respectively. RESULTS: The functional capillary density of the small intestine following ischemia and reperfusion of the left hepatic lobe significantly decreased compared to normal controls in both the mucosa and the smooth intestinal muscle. Red blood cell velocity decreased, whereas leukocyte-endothelium adherence, stasis index and the mucosal injury score increased. Administration of vasoactive intestinal polypeptide resulted in an increase of functional capillary density in the mucosa and of the red blood cell velocity and a decrease in the stasis index. The mucosal injury score was significantly higher in reperfused animals without treatment. The application of gastrin-releasing peptide resulted in an isolated increase of the red blood cell velocity. Leukocyte adherences could not be altered by the regulatory peptides. CONCLUSION: We conclude that hepatic ischemia/reperfusion injury leads to significant alterations of small bowel microcirculation and mucosal injury. Vasoactive intestinal polypeptide and gastrin-releasing peptide attenuate the damage in a different manner.

Animals↗

Microcirculation and excretory function of the liver under conditions of carbon dioxide pneumoperitoneum.

BACKGROUND: To date, the effects of increased abdominal pressure, as given during carbon dioxide (CO(2)) pneumoperitoneum, on hepatic microcirculation and biliary excretion are unknown. METHODS: Using a custom-made peritoneal cavity chamber, we performed intravital microscopy of the left liver lobe under conditions of CO(2) pneumoperitoneum in a rat model. In addition, biliary excretion was assessed. RESULTS: The establishment of a CO(2) pneumoperitoneum of 4 or 8 mmHg resulted in sinusoidal perfusion failure that was more pronounced in the periportal regions than in the midzonal and pericentral regions of the liver acinus. Biliary excretion was considerably reduced at an intraabdominal pressure of 8 mmHg. Leukocyte-endothelial cell interactions increased significantly in both hepatic sinusoids and postsinusoidal venules. CONCLUSION: Alterations in hepatic microcirculation and liver function must be taken into consideration in any kind of laparoscopic surgery and may be of particular clinical relevance in patients with liver pathology.

Animals↗

Presence of human papillomavirus-18 and Epstein-Barr virus in a squamous cell carcinoma of the tongue in a 20-year-old patient. Case report and review of the current literature.

We report on a squamous cell carcinoma of the tongue in a 20-year-old woman with co-infection of the tumor with human papilloma virus type 18 and Epstein-Barr virus. To our knowledge, this is the first case of co-infection in carcinoma of the tongue to be reported. We review the present data and theories concerning viral oncogenesis of oral carcinomas.

Adult↗

Bilateral thoracic extraadrenal myelolipoma.

Myelolipoma commonly occurs in the adrenal gland and is composed of both adipose tissue and normal hematopoietic elements. Extraadrenal myelolipoma may occur in the retroperitoneum, stomach, liver, lung, and in 3% of cases even in the mediastinum. We present a 65-year-old female patient with unspecific clinical symptoms. Routine chest roentgenograms revealed bilateral widening of the posterior mediastinum. Computed tomography showed bilateral, paravertebral lesions of 4.5 and 6.5 cm in diameter, respectively. After surgical removal, bilateral thoracic myelolipoma was pathomorphologically diagnosed. The imaging differential diagnosis of bilateral solid lesions in the posterior mediastinum including lymph node metastases, lymphomas, neurogenic tumors and extramedullary hematopoietic tumors is discussed.

Aged↗

Effect of laparotomy and CO(2) pneumoperitoneum on tumor growth of human colon carcinoma and expression pattern of tumor-associated proteins in the SCID mouse.

BACKGROUND AND AIMS: The impact of laparoscopy on tumor progression is still unclear. This study investigated the effect of CO(2) pneumoperitoneum on the intra-abdominal growth of human colon carcinoma independently of the effect of the immune system. METHODS: SCID mice underwent either median laparotomy or laparoscopy. Human colon carcinoma cells were implanted into the upper abdomen. The control group was not operated on following cell injection. Tumor growth and the protein expression pattern of proliferation marker Ki67, cell-cell adhesion molecules E-cadherin, alpha- and beta-catenin, and cell-extracellular matrix adhesion molecules CD44 v5 and v6 in tumor tissue were analyzed on postoperative day 14. RESULTS: Total tumor volume in the laparoscopy group significantly exceeded that in the laparotomy group. Immunohistochemistry revealed reduced expression of alpha-catenin and elevated expression on beta-catenin and CD44 v5 in the tumor tissue of the laparoscopy group. CONCLUSION: The expression pattern of proteins associated with tumor progression and the increase in tumor growth suggest an increased risk of laparoscopy at least for the growth of advanced human colon carcinoma.

Animals↗

A peritoneal cavity chamber for intravital microscopy of the liver under conditions of pneumoperitoneum.

BACKGROUND: Intravital microscopy allows direct visualization of the hepatic microvasculature. We report on a novel application of this technique using a chamber model that simulates the conditions of pneumoperitoneum. METHODS: For this purpose, we designed a peritoneal cavity chamber for rats. In the present study, we evaluated the technical procedure without any induction of increased intraabdominal pressure to assess undisturbed hepatic microcirculation. Intravital microscopy of the liver was performed in 12 rats. Animals that underwent the same operative procedure without the chamber served as controls (n = 12). RESULTS: Hepatic sinusoidal perfusion rate, leukocyte-endothelial cell interaction, and bile flow showed no significant differences between the groups. Operating time was longer in the chamber group. CONCLUSION: The peritoneal cavity chamber is an attractive approach for the study of hepatic microvascular, cellular, and molecular mechanisms that are important to our understanding of the potential harmful effects of laparoscopy on hepatic circulation and liver function.

Animals↗

Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours.

BACKGROUND: The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression. METHODS: Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated. RESULTS: Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0.020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0.020, P = 0.001 and P = 0.002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P < or = 0.001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0.001). Only tumours with more than five changes showed disease progression. CONCLUSION: Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.

Adult↗

[Preoperative diagnostic procedures in locally advanced rectal carcinoma (> or =T3 or N+). What does endoluminal ultrasound achieve at staging and restaging (after neoadjuvant radiochemotherapy) in contrast to computed tomography?].

INTRODUCTION: Neoadjuvant radiochemotherapy (neoRT/CT) in locally advanced rectal cancer requires an exact initial determination of the depth of the cancerous infiltration (T-status) and of locoregional lymph node metastasis (N-status). For staging and restaging, contrast-enhanced computed tomography (CT) is usually used. In specialised centers, the endorectal ultrasound (rES) may be preferred. METHODS: Between January 1998 and May 2001, the T- and N-status of 102 patients with adenocarcinoma of the rectum (> or =T3 or N+) was determined prospectively by rES and CT (group I: n=61 without neo-RT/CT, examined once; group II: n=41 examined before and after neoRT/CT). All diagnostic findings were compared using the (y)pTNM-classification. RESULTS: In the patients from group I, the depth of infiltration (uT) was predicted correctly by rES in 75% and by CT in 48% of cases; the carcinomas were understaged in 10% and 41% of cases and overstaged in 15% and 11%, respectively. According to the histopathological findings, the N-status was determined correctly by rES and CT in 75% and 57% of cases, understaging occurred in 8% and 30% and overstaging in 17% and 13%, respectively. In cases in which both methods resulted in identical T- (uT+ctT) or N-staging (uN+ctN), the accuracy increased to 82% and 80%, respectively. In patients from group II, after neoRT/CT rES and CT allowed the exact prediction of the yuT-stage in 66% and 51%, respectively. Only 2% were understaged by rES (understaging by CT: 22%). Overstaging occurred in 32% and 27% by rES and CT, respectively. The N-status determined by rES and CT was in accordance with the histopathological findings in 68% and 76%of cases, respectively. Understaging occurred in 20% and 17%,overstaging in 12% and 7%, respectively. Again identical staging results in both rES and CT increased the accuracy of the T- (yuT+yctT) or N- (yuN+yctN) classification to 90% and 83%, respectively. In group II, downsizing of the tumor by more than one T-stage was correctly assessed by rES results in 15/20 cases (75%). A complete remission of initial uT3-carcinoma was diagnosed correctly in only two of eight ypT0-cases. In contrast, CT demonstrated a remission of disease in all cases but was unable to predict the extent of tumour reduction. A remission of lymph node metastasis was accurately shown by rES in 17/19 cases (90%) and by CT in 10/12 cases (83%). CONCLUSION: The staging of pretherapeutic, locoregional T- and N-status by rES is superior to that by CT (T-status: P=0.0164, N-status: P=0.0035). At restaging, rES offers higher accuracy in the detection of residual tumour infiltration (but not significantly to CT, yT-status: P=0.0833, yN-status: P=0.7962) and assessment of local remission. Therefore rES should be the method of choice in staging to avoid overtreatment in neoadjuvant settings.After neoRT/CT, the predictive efficacy of the rES for the downsizing/-staging of rectal cancer must be evaluated on greater numbers of patients receiving standardised diagnostic procedures and therapy.

Adenocarcinoma↗

Mathematical tree models for cytogenetic development in solid tumors.

We present a new approach for modeling the occurrence of genetic changes in human tumors over time. In solid tumors, data on genetic alterations are usually only available at a single point in time, allowing no direct insight into the sequential order of genetic events. In our approach, genetic tumor development and progression is assumed to follow a probabilistic tree model. We use maximum likelihood estimation to reconstruct a tree model for the genetic evolution of a given tumor type. The use of the proposed method is illustrated by an application to cytogenetic data from 173 cases of clear cell renal cell carcinoma, which results in a model for the karyotypic evolution of this tumor.

Carcinoma, Renal Cell↗