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E de Alava

Publications and source records attributed to E de Alava.

36 records · Page 2Linked to original sources
PubMed1999

Decrease of apoptosis rate in patients with renal transplantation treated with mycophenolate mofetil.

BACKGROUND/AIMS: Mycophenolate mofetil (MMF) is a powerful immunosuppressant that inhibits the proliferation of lymphocytes by blocking the enzyme inosine monophosphate dehydrogenase. MMF prevents acute graft rejection in organ transplants. The aim of this investigation is to study whether MMF has any influence on apoptosis and proliferation rates of cells other than lymphocytes. METHODS: We conducted a retrospective study of renal allograft biopsies taken during the 1st week after transplantation in 25 patients receiving triple therapy with prednisone, ciclosporin and azathioprine 75 mg/day and in 25 patients treated with MMF at a dose of 2 g/day instead of azathioprine, in order to investigate the differences in the proliferation and apoptosis rates of the glomerular, tubular, interstitial and endothelial cells of the kidney. Twelve normal kidneys were used as controls. Conventional histopathological techniques were applied as usual for pathological diagnosis. Proliferative activity was assessed by use of MIB-1 antibody. Sections of formalin-fixed, paraffin-embedded tissue blocks were stained for the presence of apoptotic cells by TUNEL assay. Evaluation of proliferative or apoptotic rates was made by counting the number of positive cells in 10 glomeruli and in 10 transversely cut tubuli in each biopsy. The positive cells in the interstitium were counted in ten high-power fields. Positive cells in the endothelium were scored semiquantitatively from 0 to 3: 0 = none, 1 = isolated cells, 2 = small groups of cells, 3 = most endothelial cells. Mann-Whitney U and chi-square tests were used for intergroup comparisons. RESULTS: All biopsies were normal or had borderline (Banff classification) acute rejection. MIB-1 rates were similar in both groups, without statistical differences (p > 0.05) between them. Significantly lower apoptotic rates were found in the group treated with MMF in tubular epithelium (23.41 +/- 8.86 vs. 57.4 +/- 13.42; p = 0.021), in glomerular (1.25 +/- 0.78 vs. 5.3 +/- 1.66; p = 0.027), and interstitial cells (1.58 +/- 0.6 vs. 5.8 +/- 1.54; p = 0.043). Apoptosis in endothelial cells (p > 0.05) was similar in both groups. CONCLUSION: We conclude that treatment with MMF of kidney transplant patients does not affect the proliferative rate of cells of the allograft, but decreases the number of apoptotic cells in tubular epithelium.

Adult↗
PubMed1999

EWS-FLI1 and EWS-ERG gene fusions are associated with similar clinical phenotypes in Ewing's sarcoma.

PURPOSE: There are a variety of solid tumors in which alternative chromosomal translocations generate related fusion products. In alveolar rhabdomyosarcoma and synovial sarcoma, these variant fusions have been found to have major clinical significance. We investigated whether the two alternative gene fusion products, EWS-FLI1 and EWS-ERG, define different clinical subsets within the Ewing's sarcoma family of tumors. PATIENTS AND METHODS: We selected 30 cases of Ewing's sarcoma with the EWS-ERG gene fusion and 106 cases with the EWS-FLI1 fusion. Clinical data were obtained for each case and compared with the molecular diagnostic findings. RESULTS: There were no significant clinical differences observed between the two groups in age of diagnosis, sex, metastasis at diagnosis, primary site, event-free survival, or overall survival. CONCLUSION: Differences in the C-terminal partner in the Ewing's sarcoma family gene fusions are not associated with significant phenotypic differences.

Adolescent↗
PubMed1998

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation.

We report a case of a 13-year-old girl with soft tissue sarcoma of the hand, which showed muscle and neuroectodermal immunophenotypes. Molecular studies were performed on RNA collected from fine-needle aspiration (FNA) cytology and peripheral blood samples by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. This biphenotypic tumor showed simultaneous expression of EWS-FLI1 and PAX3-FKHR transcripts, specific of Ewing family tumors and alveolar rhabdomyosarcoma, respectively. Although childhood sarcomas with simultaneous muscle and neural differentiation have been described to have EWS-FLI1 transcripts, there are no reports of tumors with both transcripts. Cytological specimens are a good source of RNA for molecular studies.

Adolescent↗
PubMed1998

CD44v6 expression is related to progression in renal epithelial tumours.

AIMS: Expression of CD44 variant isoform including exon 6 has been associated to tumour progression in several carcinomas. However, no studies have been performed to assess the prognostic value of the expression of this marker in renal cell tumours. METHODS AND RESULTS: We studied 58 renal cell tumours. All patients were followed up for at least 3 years after nephrectomy. Tumours were analysed for expression of CD44v6 assessed by two isoform-specific monoclonal antibodies. RT-PCR was performed to detect CD44 variant transcripts in 10 cases in which immunohistochemistry was negative. Twenty-two tumours showed reactivity in at least 1% cells for both antibodies with a strong membrane pattern. RT-PCR did not show CD44v6 transcripts in any of 10 studied tumours. Immunohistochemical staining was more frequent in perivascular areas or in areas of vascular invasion. In fact, CD44v6 expression correlated well with nuclear grade (P = 0.009), stage at diagnosis (P = 0.04) and appearance of metastasis after nephrectomy (P = 0.007). Although univariate survival analysis showed stage (P < 0.001), grade (P = 0.009) and CD44v6 expression (P = 0.04) to be significant predictive factors, only stage remained significant (P = 0.0013) in the multivariate analysis. CONCLUSIONS: CD44v6 expression, assessed immunohistochemically, is related to tumour progression. However, its prognostic value in renal cell tumours is dependent on tumour stage at diagnosis.

Carcinoma↗
PubMed1998

Intraabdominal desmoplastic small round cell tumor with EWS/ERG fusion transcript.

This report describes an intraabdominal small cell tumor in a 37-year-old woman, with clinical, topographic, and morphologic features highly suggestive of the desmoplastic small round cell tumor. Immunohistochemical analysis revealed a polyphenotypic profile consistent with this tumor--positivity for keratin, epithelial membrane antigen, neuron-specific enolase, vimentin, and desmin--but, in addition, a strong membranous immunoreactivity for CD99 (MIC2 protein). Reverse transcription polymerase chain reaction revealed a EWS/ERG fusion transcript characteristic of the Ewing's sarcoma/peripheral primitive neuroectodermal tumor group of tumors, rather than the EWS/WT1 chimeric transcript typical of the desmoplastic small round cell tumor. This is the third report of a hybrid tumor with features of the desmoplastic small round cell tumor and Ewing's sarcoma/peripheral primitive neuroectodermal tumor, and the first one with the EWS/ERG fusion gene. Our case shows the existence of some overlap between these two groups of tumors, which are considered to be histogenetically different, and the need for further studies of molecular characterization of small cell tumors, especially in those with atypical morphologic or immunohistochemical features.

Abdominal Neoplasms↗
PubMed1998

Ewing family tumors: potential prognostic value of reverse-transcriptase polymerase chain reaction detection of minimal residual disease in peripheral blood samples.

In more than 95% of patients, the Ewing family of tumors (ET) has chimeric transcripts caused by fusion of the EWS gene to either FLI1 or ERG. The presence of specific EWS-FLI1 or EWS-ERG transcripts in peripheral blood (PB) samples of patients being treated for ET was prospectively evaluated, and these data were correlated to their clinical status. The authors studied 113 PB samples from 28 patients with ET. Treatment included chemotherapy, radiotherapy, and surgical excision of tumor after induction therapy. PB samples were taken prospectively at least 2 weeks after resection of tumor. Nested reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot was performed in all samples. Resected tumors were reviewed for the degree of response to chemotherapy and volume. Seventy-seven PB samples from 28 patients had EWS-FLI1/ERG transcripts. In 11 patients, PB samples became negative with treatment, and, in 5 of them, the samples remained negative throughout the study. Samples taken during progression were always positive and, in 4 patients, became positive before progression was clinically evident. All patients with transcripts other than EWS-FLI1 type 1 (n = 3) died from tumor progression. This is a sensitive assay to monitor circulating tumor cells in Ewing tumors. The preliminary data suggest that progression is preceded by positive samples and may be related to specific transcript types.

Adolescent↗
PubMed1998

EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

PURPOSE: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance. PATIENTS AND METHODS: We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage. RESULTS: Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis. CONCLUSION: EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon.

Adolescent↗
PubMed1998

Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants.

PURPOSE: Intense investigation has reshaped concepts about undifferentiated tumors occurring in young people (small round-cell tumors). Tumors associated with t(11;22)(p13;q12) and descriptively designated desmoplastic small round-cell tumor (DSRCT) are a distinctive, rare, poorly understood member of this family. We reviewed 109 cases of DSRCT to further characterize this entity better. METHODS: Clinical information and histology were reviewed. Immunohistochemistry and immunoblotting were performed using standard techniques. Chimeric EWS-WT1 RNA and DNA were detected by polymerase chain reaction (PCR) and genomic translocation breakpoints mapped in a subset of cases. RESULTS: There were 90 males and 19 females from 6 to 49 years of age (mean, 22 years). A total of 103 had tumor in the abdominal cavity, four in the thoracic region, one in the posterior cranial fossa, and one in the hand. Typical histologic and immunohistochemical features were usually evident in well-sampled tumors, but variations in cellularity, stromal components, cytology, architecture, and immunoreactivity occurred. Tumor cells were usually reactive with antibodies to keratin (67 of 78 cases, 86%), epithelial membrane antigen (50 of 54, 93%), vimentin (64 of 66, 97%), desmin (70 of 78, 90%), neuron-specific enolase (60 of 74, 81%), and the EWS-WT1 chimeric protein (25 of 27, 93%); typically nonreactive for muscle common actin (one of 58, 2%), myogenin (zero of eight, 0%), and chromogranin (one of 46, 2%); and variably reactive for MIC2 (nine of 47, 20%) and p53 (five of 17 with > 20% tumor cells reactive). Functional EWS-WT1 gene fusion was evident in 25 of 26 cases with genomic breakpoints in WT1 intron 7, and EWS introns 7, 8, and 9. Prognosis in general is poor, but tumors are responsive to aggressive therapy. CONCLUSION: This large review identifies a greater degree of clinical, pathologic, and molecular variation than originally appreciated for tumors associated with t(11;22)(p13;q12). Translocation and functional fusion of the EWS and WT1 genes appears to be a consistent feature of this unique tumor.

Abdominal Neoplasms↗
PubMed1995

Detection of chimeric transcripts in desmoplastic small round cell tumor and related developmental tumors by reverse transcriptase polymerase chain reaction. A specific diagnostic assay.

Desmoplastic small round cell tumor is a recently described entity associated with fusion of the EWS and WT1 genes and with expression of a chimeric transcript. To investigate the structure and potential diagnostic utility of the detection of EWS-WT1 chimeric RNA in desmoplastic small round cell tumor, 12 examples of this entity and 49 other tumors that enter in its differential diagnosis were studied by reverse transcriptase polymerase chain reaction for the presence of EWS-WT1, EWS-FLI-1, PAX3-FKHR, and PAX7-FKHR chimeric transcripts. EWS-WT1 was detected in 11 of 12 desmoplastic small round cell tumors but not in any other tumor type studied, including 17 Wilms' tumors, 10 Ewing's sarcomas/primitive neuroectodermal tumors, 13 alveolar rhabdomyosarcomas, and 9 embryonal rhabdomyosarcomas. One desmoplastic small round cell tumor was found to have a variant EWS-WT1 chimeric product that included exon 8 of EWS EWS-FLI-1 chimeric RNA was present in all Ewing's sarcoma/primitive neuroectodermal tumor and not identified in any other tumor types, including desmoplastic small round cell tumor. PAX3/PAX7-FKHR chimeras were present in 9 of 13 alveolar rhabdomyosarcomas but not in any other tumors. Detection of chimeric transcripts by reverse transcriptase polymerase chain reaction is a very specific aid in differential diagnosis of developmental tumors and further establishes desmoplastic small round cell tumor as a distinct entity.

Adolescent↗
PubMed1994

Prediction of sustained remission of chronic hepatitis C after a 12-month course of alfa interferon.

alpha-Interferon therapy normalizes aminotransferase levels in approximately 50% of the patients with chronic hepatitis C, but post-therapy relapses are common and predictive factors of sustained response remain largely unknown. We retrospectively assessed several parameters as predictors of sustained remission after a 12-month course of lymphoblastoid alpha-interferon: the Knodell histological activity index, serum levels of procollagen type III peptide, serum HCV-RNA, anti-alpha-interferon antibodies, and anti-HCV antibodies (C-100-3), all at month 12. Thirty-seven patients were studied. Fourteen patients were non-responders (38%), 15 patients experienced a sustained response (40.5%) and eight patients responded similarly but relapsed after alpha-interferon withdrawal (21.5%). A decrease in the histological activity index above 5, normalization of procollagen type III peptide levels (< 12 ng/ml) and the absence of viremia after treatment were all significantly associated with a sustained response (p = 0.008, p = 0.007 and p = 0.037, respectively). Anti-interferon antibodies were detected in only one non-responder patient. Anti-C-100-3 antibodies became undetectable at month 12 in 5 of the 15 sustained responders. The best prediction of sustained response was obtained from the three variables independent of multivariate analysis according to the following equation: F = 0.872 + 0.067 x K (decrease of histological index) -0.052 x P (procollagen type III peptide levels at month 12) -0.28 x R (HCV-RNA at month 12; R = 2 when present and R = 1 when absent). A score higher than 0 predicted sustained remission with a 100% sensitivity and specificity in this series of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Leiomyosarcoma of the pancreas.

We report a case of leiomyosarcoma of the pancreas. A spindle cell pattern at light microscopy, immunocytochemical reactivity with desmin, alpha-1-antitrypsin, vimentin and actin and ultrastructural features of smooth muscle differentiation help to establish the diagnosis.

Aged↗
PubMed1993

Histological outcome of chronic hepatitis C treated with a 12-month course of lymphoblastoid alfa interferon.

To assess the effect of long-term alfa interferon therapy (12 months) on liver histology of chronic hepatitis C, we studied 61 treated patients, and compared their outcome with 28 untreated cases followed as controls. A liver biopsy was taken from all patients, before (month 0) and after the completion of the treatment or the control period (month 12). A third liver specimen taken at month 24 was available in 29 treated cases. Liver biopsies were blindly graded following Knodell's method. In 33 out of the 61 treated patients (54.1%), aminotransferase levels became normal shortly after starting therapy and remained within normal values until the end of treatment (sustained response). Nine (27%) sustained responders relapsed after interferon discontinuation, while the remaining 24 (73%) continued with normal aminotransferase values during follow-up (16.8 +/- 9.9 months). All histological parameters, except fibrosis, improved significantly after 12 months of therapy (periportal necrosis, month 0: 2.7 +/- 1.0, month 12: 1.6 +/- 1.1, p < 0.0001; lobular damage, month 0: 2.5 +/- 1.1, month 12: 1.4 +/- 0.9, p < 0.0001; portal inflammation, month 0: 3.6 +/- 0.5, month 12: 3.0 +/- 0.9, p < 0.0001). Histological improvement was especially marked in patients who did not relapse, although those who relapsed and partial responders also improved. Overall histological diagnoses improved in most patients. A sustained response to interferon was predicted by high periportal and lobular scores, and by a low fibrosis score on the pretreatment liver biopsy. At 24 months, histological improvement persisted in patients without posttreatment relapse, while liver inflammation had returned to pretreatment levels in the remaining cases.

Adult↗
PubMed1993

[Aneurysm of the ascending aorta in patients with a prior aortic valve replacement].

INTRODUCTION AND OBJECTIVES: The purpose of this study is to show our experience in the treatment of aneurysms of the ascending aorta in patients with previous aortic valve surgery. METHODS: We studied retrospectively the clinical characteristics and operative methods of 9 patients who underwent surgery for aneurysm of the ascending aorta after previous aortic valve replacement. RESULTS: Time interval between the first and subsequent reoperation was 8.4 +/- 3.5 years (range 4-15 years). During the first operation there were 5 cases who presented with aortic regurgitation and dilatation of the ascending aorta. Isolated valvular aortic replacement was performed in these patients. Two patients underwent valvular replacement and implantation of supracoronary aortic graft. In two other cases valvular replacement was done with wedge resection of the aortic sinuses. Reoperation was performed because to the following reasons: valvular prosthesis disfunction and aneurysm of the ascending aorta (3), valvular prosthesis disfunction and aneurysm of the aortic remnant located between the prosthesis and the supracoronary aortic graft (2), thrombosis of the prosthesis (1), dissection of the ascending aorta (2) and superior vena cava syndrome (1). There was one hospital death. Another patient died after 26 months because of graft infection. The other 7 patients are in functional class I. CONCLUSIONS: We conclude that an aggressive surgical approach should be adopted in patients with degenerative aortic regurgitation and moderate dilatation of the ascending aorta because of the rapid progression of the aortic disease. We advise complete replacement of the aortic root.

Adult↗
PubMed1992

Pathology of heart transplant through endomyocardial biopsy.

Cardiac transplantation is most effective method for treatment of patients with end-stage heart disease. We present the experience of our institution with 1,564 biopsies and 11 autopsies of 105 orthotopic heart transplants. This report describes the morphological features and the grading systems of acute rejection. Also, we present the morphological characteristics of other complications of heart transplants such as chronic rejection, "Quilty" effect, interstitial fibrosis, heart hypertrophy, previous biopsy sites, calcification, cytomegalovirus infections, toxoplasmosis, and the appearance of malignancies, mainly, lymphomas. Actuarial survival of patients is 91% and 88% at 1 and 5 years' posttransplant, respectively.

Adolescent↗
PubMedDate not supplied

[Pathological anatomy of organ transplantation].

We review some morphological aspects shared by all allografts. The main points are: 1) The expression of antigens of histocompatibility, essentially DR, allows the diagnosis of acute rejection with a significant specificity; 2) A lesion similar to "Quilty" effect may be seen in other allografts, and it is the first manifestation of an acute rejection; 3) Fine-needle aspiration biopsy may help in the follow-up of kidney transplant but has been demonstrated ineffective in other transplants; 4) The morphology of rejection is different according to the type of immunosuppressive therapy; 5) The basic lesions of chronic rejection are vascular, but chronic rejection may be diagnosed without vessels in the biopsy specimen, by the degree of atrophy of the parenchyma; 6) For the characterization of lymphomas in transplanted patients is necessary study the clonality of tumor cells, the gene rearrangement and the lymphoid subset; 7) Molecular Pathology may help in the early diagnosis of viral infections after transplantation.

Atrophy↗