Biomedical subjects

J Diebold

Publications and source records attributed to J Diebold.

At least 19 recordsLinked to original sources

PubMed2000

Prognostic significance of survivin expression in diffuse large B-cell lymphomas.

Survivin is an inhibitor of apoptosis overexpressed in various human cancers but undetectable in normal differentiated tissues. A potential expression and prognostic significance of survivin was studied in 222 patients with diffuse large B-cell lymphomas (centroblastic, 96%; immunoblastic, 4%). All patients were enrolled between 1987 and 1993 (median follow-up, 7 years) in the LNH87 protocol of the Groupe d'Etudes des Lymphomes de l'Adulte (GELA) and treated either with the reference ACVBP arm (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone)[AU3A] (n = 79) or other experimental anthracycline-containing regimens (n = 143). The characteristics of these patients were median age of 56 years; serum lactate dehydrogenase (LDH) greater than 1N, 60%; stage III-IV, 55%; performance status, according to the Eastern Cooperative Oncology Group (ECOG) scale, more than 1, 23%; extranodal sites more than 1, 29%; mass more than 10 cm, 44%; bone marrow involvement, 15%. Of the 222 patients studied, 134 (60%) revealed survivin expression in virtually all tumor cells by immunohistochemistry. The overall 5-year survival rate was significantly lower in patients with survivin expression than in those without (40% vs 54%, P =.02). Multivariate analysis incorporating prognostic factors from the International Prognostic Index (IPI) identified survivin expression as an independent predictive parameter on survival (P =.03, relative risk [RR] = 1.6) in addition to LDH (P =.02, RR = 1.6), stage (P =.03, RR = 1.7), and ECOG scale (P =.05, RR = 1.6). A second analysis incorporating IPI as a unique parameter demonstrated that survivin expression (P =.02, RR = 1.6) remained a prognostic factor for survival independently of IPI (P =.001, RR = 1.5). Survivin expression may be considered a new unfavorable prognostic factor of diffuse large B-cell lymphoma. (Blood. 2000;96:1921-1925)

Adolescent↗

PubMed2000

Photodetection of cervical intraepithelial neoplasia using 5-aminolevulinic acid-induced porphyrin fluorescence.

BACKGROUND: Screening for cervical carcinoma and its precursors is based on cervical cytology and diagnostic colposcopy. Despite the decrease in the incidence of cervical carcinoma in countries with a good screening program, this rate of decline is leveling off. Known problems are false-negative rates of cytology and low specificity of colposcopy. This clinical study examined the diagnostic potential of porphyrin fluorescence in patients with cervical intraepithelial neoplasia Grade 1-3 (CIN 1-3). METHODS: Sixty-eight women attending our colposcopy clinic underwent a gynecologic examination, including cytology, human papillomavirus (HPV) testing, and colposcopy. They received 10 mL 0.5% or 1.0% 5-aminolevulinic acid (5-ALA) topically. After 30-360 minutes, real-time image analysis was performed, and spectra were obtained from 685 sites. RESULTS: Due to rapid photobleaching, 0.5% 5-ALA proved ineffective for fluorescence assessment. Using 1% 5-ALA, the authors found that fluorescence intensities correlated with incubation time; however, fluorescence contrast showed a maximum at 60-90 minutes (ratio 11:1). HPV DNA positive lesions showed significantly higher fluorescence. Fluorescence imaging after 60-90 minutes achieved similar sensitivity and specificity compared with colposcopy in detecting CIN with 94% and 51% versus 95% and 50%, respectively. However, the specificity was markedly improved by fluorescence spectroscopy, achieving 75%. The evaluation of spectral measurements revealed significantly higher values for CIN compared with normal tissue and for CIN 2/3 compared with CIN 1 (P < 0.001). CONCLUSIONS: Using a time interval of 60-90 minutes after topical application of 1% 5-ALA, the authors observed specific porphyrin fluorescence of CIN. Fluorescence spectroscopy promises to become a valuable tool for the diagnosis of CIN.

Adult↗

PubMed2000

Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid.

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat.

Adult↗

PubMed2000

20q13 and cyclin D1 in ovarian carcinomas. Analysis by fluorescence in situ hybridization.

In ovarian carcinomas, alterations of the chromosomal region 20q13 and the cyclin D1 gene have been described. This study has sought to determine their prognostic significance. Fluorescence in situ hybridization (FISH) on dissociated nuclei and paraffin sections with DNA probes for 20q13.2 and cyclin D1, as well as immunohistochemistry (cyclin D1), were applied to formalin-fixed tissue of 69 invasive ovarian carcinomas, mainly of serous type. On dissociated nuclei 33/47 cases (70%) and on tissue sections 13/66 cases (20%) demonstrated an increase of 20q13.2 copies. The presence of > or =4 copies per nucleus (isolated nuclei) and > or =3 copies per nucleus (sections) was associated with an adverse prognosis (Kaplan-Meier for FIGO stage III after stratification for residual tumour: p=0.0049 and p=0.03, respectively). Thirty-four out of 47 cases (72%) showed an increase of cyclin D1 copies. Kaplan-Meier analysis for FIGO stage III after stratification for residual tumour>2 cm or < or =2 cm revealed an unfavourable outcome for cases with more than two cyclin D1 copies (p=0.04). No correlation was seen between FISH and immunohistochemistry. Multivariate analysis identified residual tumour (p=0.0002), 20q13.2 gain (p=0.0004) and cyclin D1 gain (p=0.0343) as independent prognostic factors. It is concluded that gains of chromosomal region 20q13.2 and the cyclin D1 gene are frequent and biologically important events, with prognostic relevance, in advanced ovarian carcinomas.

Adult↗

PubMed2000

In vitro-generated stem cell leukaemia showing altered cell cycle progression with distinct signalling of the tyrosine-phosphorylated rasGAP-associated p62(dok) protein.

In an attempt to gain more insight into the events of leukaemic transformation, a cell line overexpressing MHC class II (DR) was generated by transfecting an early CD34-negative haematopoietic progenitor stem cell line with the appropriate constructs. The stable transfection with genes for DR antigens leads to cellular transformation. The DR(+) transformed cell clones express a tyrosine-phosphorylated DR heterodimer and show a significantly different morphology. DR(+) clones present the morphology of an immature myeloid neoplasia expressing alpha-naphthyl-acetate-esterase (ANAE), but neither myeloperoxidase nor CD34. While D064 cells predominately grow adherent as fibroblast-like cells, the DR(+) clones display a decrease in adherent growth. Although both cell lines express similar amounts of the interleukin-6 (IL-6) signal transducer gp130, the DR-transfected cells still show activation of STAT factors by IL-6, whereas D064 cells do not. Although the transformed clones present acceleration of cell-cycle transition and growth, the G(0)/G(1) progression inhibitor p27(kip-1) is up-regulated, while the expression of proteins involved in the S/G(2) phase transition, such as cyclin B and cdc2 (p34), is suppressed. Instead cyclin D3, one of the G(0)/G(1) progression factors, is up-regulated, as well as tyrosine-phosphorylated p62(dok), suggesting dysregulation of cell cycle-controlling proteins. In addition, DR(+) leukaemia-like cells also overexpress Bcl-2, while bax expression is suppressed, compared with the wild-type (wt) parental haematopoietic stem cell line.

Acute Disease↗

PubMed2000

Immunohistochemical analysis of drug resistance-associated proteins in ovarian carcinomas.

Loss of function of the tumor suppressor gene p53, increased expression of glutathione-S-transferase pi (GST7pi) and the major vault protein are involved in drug resistance of ovarian carcinomas. However, a study comparing these factors has not yet been performed. Therefore, paraffin-embedded material of 213 ovarian tumors with well-documented follow-up was used for immunohistochemical analysis of p53 protein, GSTpi, and major vault protein (antibodies LRP-56, LMR-5). Forty-six percent of the cases showed nuclear p53 accumulation. Strong immunoreactivity for GSTpi, LRP-56, and LMR-5 was seen in 50%, 36%, and 47%, respectively. p53 positivity was most often found in serous carcinomas (p < 0.05). Strong GSTpi expression was the only factor that correlated with clinical resistance to chemotherapy (p = 0.04). In the whole group, as well as in FIGO III cases stratified for residual disease < or = and >2 cm, p53 and GSTpi correlated with an adverse outcome (p = 0.01 for p53 and p = 0.04 for GSTpi). Strong LRP-56 or LMR-5 staining was associated with a tendency towards poorer prognosis, without reaching statistical significance. In multivariate analysis for FIGO III, only residual disease and p53 proved to be independent prognostic factors. Our observations confirm the prognostic significance of p53 accumulation in ovarian carcinomas. Only GSTpi immunoreactivity was significantly correlated with drug resistance.

Adenocarcinoma, Mucinous↗

PubMed2000

Quality control and sensitivity of polymerase chain reaction techniques for the assessment of immunoglobulin heavy chain gene rearrangements from fixed- and paraffin-embedded samples.

Frozen tissue is considered the gold standard if DNA is to be extracted for polymerase chain reaction (PCR) analysis. In molecular studies from paraffin-embedded material, only positive results are usually taken into account. Our goal was to evaluate both the sensitivity and the specificity of PCR techniques for immunoglobulin heavy chain (IgH) gene rearrangement according to various lengths and types of fixative before paraffin embedding. One set of studies compared IgH rearrangement in a case of mantle cell lymphoma tissue that had been fixed in 14 different ways before paraffin embedding and frozen tissue. Formalin fixation was found not to be deleterious for DNA, amplification being possible up to 15 days after fixation with good sensitivity. In contrast, the performance of PCR decreased for samples fixed in Bouin's liquid for longer than 6 hours or after 48 hours of incubation in a vacuum infiltration processor (in which Bouin's liquid-fixed and formalin-fixed samples are mixed). In addition, we undertook a retrospective study of 20 routinely processed B-cell lymphomas, with frozen formalin-fixed and Bouin's liquid-fixed tissues for each case. Of the 14 positive cases on frozen material, 13 were also clonal from paraffin-embedded tissues. Whatever the IgH locus analyzed, each time the adapted control was positive, results from paraffin-embedded material were identical to results obtained from frozen tissue. In this study, we showed that the use of paraffin-embedded tissue is efficient for the study of IgH gene rearrangement. Whenever adapted controls are used, it is even possible to assess negative results.

DNA Primers↗

PubMed2000

FISH analysis of gene aberrations (MYC, CCND1, ERBB2, RB, and AR) in advanced prostatic carcinomas before and after androgen deprivation therapy.

Genetic mechanisms leading to androgen-independent growth in advanced prostatic carcinomas (PC) are still poorly understood. Analysis of genes potentially involved in the regulation of tumor cell proliferation and apoptosis might confer better insight into this process and might lead to improved therapeutic strategies. Fluorescence in situ hybridization (FISH) analysis of dissociated nuclei with DNA probes for MYC (8q24)/#8, cyclin D1 gene (CCND1; 11q13)/#11, ERBB2 (17q13)/#17, the androgen receptor gene (AR; Xq12)/#X, and the retinoblastoma gene (RB; 13q14) was applied to formalin-fixed tissue from 63 patients with advanced PC after androgen deprivation therapy (ADT); matched tumor tissue before ADT was also available in 22 of these cases. The cut-points used were: "increased copy number," > or = 30% of all nuclei with increased FISH signals (centromere and/or gene); "amplification," > or = 15% of nuclei with "increased gene copy number." CCND1 and MYC gene "amplifications" were present before ADT in 25% and 33% of the cases, respectively; the frequency of these "amplifications" increased to 37% and 57% after ADT. Loss of the RB gene was nearly four times more frequent after ADT than before therapy (22% versus 6%). AR and ERBB2 gene "amplifications" occurred only after ADT in 36% and 30% of cases, respectively. With the exception of the AR gene, the copy number increase was low. After treatment, MYC and AR gene "amplifications" correlated with the proliferation rate (Ki-67/MIB1 index; p = 0.01 and p = 0.04), whereas ERBB2 "amplifications" were associated with increased apoptotic index (PCD/TUNEL; p = 0.016). However, no correlation between FISH results and clinical follow-up could be established. FISH analysis of genes putatively involved in PC progression revealed characteristic patterns of aberrations in advanced PC before and after ADT. Distinct changes in gene copy number before and after therapy suggests possible involvement of these genes in the escape from androgen control.

Aged↗

PubMed2000

The World Health Organization classification of hematological malignancies report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997.

Since 1995, the European Association of Pathologists and the Society for Hematopathology have been developing a new World Health Organization (WHO) classification of hematologic malignancies. The classification includes lymphoid, myeloid, histiocytic, and mast cell neoplasms. The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee of international hematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November 1997 to discuss clinical issues related to the classification. The WHO has adopted the Revised European-American Classification of Lymphoid Neoplasms, published in 1994 by the International Lymphoma Study Group, as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of "real" disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one "gold standard." The WHO classification has applied the principles of the Revised European-American Classification of Lymphoid Neoplasms to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The Clinical Advisory Committee meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail in this article. Among other things, the Clinical Advisory Committee concluded that clinical grouping of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the international prognostic index. The experience of developing the WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world. This should facilitate progress in the understanding and treatment of hematologic malignancies.

Hematologic Neoplasms↗

PubMed2000

The World Health Organization classification of neoplastic diseases of the haematopoietic and lymphoid tissues: Report of the Clinical Advisory Committee Meeting, Airlie House, Virginia, November 1997.

INTRODUCTION: Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) classification of haematological malignancies. The classification includes lymphoid, myeloid, histiocytic and mast cell neoplasms. DESIGN: The WHO project involves 10 committees of pathologists, who have developed lists and definitions of disease entities. A Clinical Advisory Committee (CAC) of international haematologists and oncologists was formed to ensure that the classification will be useful to clinicians. A meeting was held in November 1997 to discuss clinical issues related to the classification. RESULTS: The WHO has adopted the 'Revised European-American Classification of Lymphoid Neoplasms' (REAL), published in 1994 by the International Lymphoma Study Group (ILSG), as the classification of lymphoid neoplasms. This approach to classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. The WHO classification has applied the principles of the REAL classification to myeloid and histiocytic neoplasms. The classification of myeloid neoplasms recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. The CAC meeting, which was organized around a series of clinical questions, was able to reach a consensus on most of the questions posed. The questions and the consensus are discussed in detail below. Among other things, the CAC concluded that clinical groupings of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumour type, if applicable, and clinical prognostic factors such as the international prognostic index (IPI). CONCLUSION: The experience of developing the WHO classification has produced a new and exciting degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of haematological malignancies.

Hematologic Neoplasms↗

PubMed2000

Bone marrow manifestations of infections and systemic diseases observed in bone marrow trephine biopsy review.

Bone marrow modifications resulting from infections and systemic diseases can be studied by analysis of morphology and aetiology. Two types of lesions or modifications can be observed, those occurring in the connective tissue comprising inflammatory processes, acute and chronic, as well as immune reactions, and those involving the normal haematopoietic cell lines, with possible hyperplastic or aplastic changes in one or more cell lines. The main lesions are described (oedema, haemorrhage, necrosis, suppuration, granulomas, lymphoid nodules and hyperplasia, immunoblastic or plasmacytic hyperplasia), as well as the main aetiologies. In association, the three main haematopoietic cell lines show hyperplasia, hypoplasia, aplasia of one or all of the cell lines, sometimes with dysmyelopoiesis. The stroma and vessel reactions comprise myelofibrosis, gelatinous transformation or amyloid deposits. The methods for identifying aetiological agents are emphasized. It should also be stressed that malignant neoplasias of different types involving the bone marrow can be responsible for such inflammatory or immune reactions.

Bacterial Infections↗

PubMed2000

Splenic marginal zone lymphoma with or without plasmacytic differentiation.

We report a series of 31 cases of splenic marginal zone lymphomas with an enlarged spleen and a multimicronodular macroscopic pattern. Two groups, A and B, were distinguished based on the presence (A) or absence (B) of a lymphoplasmacytic component with monoclonal immunoglobulin expression in the cytoplasm. There were no differences between the groups as far as age, sex, spleen weight, and progression. The only difference was the presence in group A of a monoclonal serum component and autoimmune disorders, particularly autoimmune hemolytic anemia. In most cases in which a liver and/or bone marrow biopsy was performed, lymphomatous infiltration was detected. Seven cases had a seric monoclonal IgM of 5 g/L or more and liver or bone marrow infiltration, corresponding to the definition of Waldenstrom's macroglobulinemia. Lymphoma cells had a monocytoid, centrocytoid and, in group A, lymphoplasmacytic morphology. The lymphomatous cells were positive for CD20, CD45 RA, and bcl-2. They expressed IgD in 9 cases, partially in 6, and were negative for IgD in 9 of the 24 cases studied. Progression seems to be slow, with a long survival. Three patients presented with transformation into a large B-cell lymphoma, which was responsible for death in two patients.

Adult↗

PubMed2000

Grading of ovarian carcinomas.

Grading of ovarian carcinomas can have important implications for therapeutic decisions, in particular in International Federation of Gynecology and Obstetrics (FIGO) stage I. However, there are no universally accepted grading guidelines for this type of cancer. We applied the grading system suggested by Shimizu et al. (1) to a series of ovarian carcinomas from a single institution to evaluate its prognostic significance in relation to other predictive factors. One hundred ninety-two cases of ovarian carcinomas were studied, including all major histologic types. The histologic slides were evaluated with regard to architecture (glandular = 1 point, papillary = 2 points, solid = 3 points), nuclear pleomorphism (nuclear variability < or = 2:1 = 1 point, intermediate nuclei = 2 points, nuclear variability > or = 4:1 = 3 points), and mitotic activity per 10 high-power fields using objective 40x, ocular 10x/20 (0-7 mitoses = 1 point, 8-18 mitoses = 2 points, > or = 9 mitoses = 3 points). Carcinomas with a total score of 3-5 points were designated as grade I, 6-7 points were designated as grade II, and 8-9 points were designated as grade III. Kaplan-Meier curves showed the following 5-year survival rates: grade I (n = 42) 88%, grade II (n = 98) 60%, grade III (n = 52) 38% (p < 0.0001); stage I 90%, stage II 60%, stage III 38%, stage IV 10% (p < 0.0001); residual disease < or = 2 cm 67% and > or = 2 cm 27% (p < 0.0001). Multivariate Cox analysis revealed that grade (p < 0.0002), as well as nuclear pleomorphism alone (p < 0.0001), both provided statistically significant independent prognostic information. Our observations showed that the grading system used can be easily applied to all histologic types of ovarian carcinomas yielding prognostically relevant information and can be incorporated into routine diagnostic practice.

Adenocarcinoma, Clear Cell↗

PubMed2000

Interferon consensus sequence binding protein confers resistance against Yersinia enterocolitica.

Interferon consensus sequence binding protein (ICSBP)-deficient mice display enhanced susceptibility to intracellular pathogens. At least two distinct immunoregulatory defects are responsible for this phenotype. First, diminished production of reactive oxygen intermediates in macrophages results in impaired intracellular killing of microorganisms. Second, defective early interleukin-12 (IL-12) production upon microbial challenge leads to a failure in gamma interferon (IFN-gamma) induction and subsequently in T helper 1 immune responses. Here, we investigated the role of ICSBP in resistance against the extracellular bacterium Yersinia enterocolitica. ICSBP(-/-) mice failed to produce IL-12 and IFN-gamma, but also IL-4, after Yersinia challenge. In addition, granuloma formation was highly disturbed in infected ICSBP(-/-) mice, leading to multiple necrotic abscesses in affected organs. Consequently, ICSBP(-/-) mice rapidly succumbed to acute Yersinia infection. In vitro treatment of spleen cells from ICSBP(-/-) mice with recombinant IL-12 (rIL-12) or rIL-18 in combination with a second stimulus resulted in IFN-gamma induction. In experimental therapy of infected ICSBP(-/-) mice, we observed that administration of rIL-12 induced IFN-gamma production which was associated with improved resistance to Yersinia. In contrast, treatment with rIL-18 failed to enhance endogenous IFN-gamma production but nevertheless reduced bacterial burden in ICSBP(-/-) mice. Although cytokine therapy with rIL-12 or rIL-18 ameliorated the course of Yersinia infection in ICSBP(-/-) mice, both cytokines failed to completely restore impaired immunity. Taken together, the results indicate that the transcription factor ICSBP is essential for efficient host immune defense against Yersinia. These results are important for understanding the complex host immune responses in bacterial infections.

Animals↗

PubMed2000

[Fragmentation of hydrogel episcleral implants: a series of 4 cases].

A histopathologic study was performed on 4 capsule specimens obtained after surgical removal of hydrogel episcleral implant previously sutured to the scleral surface aiming to reattach the retina. Fragments of hydrogel were found on the inner surface of the capsular fragments, each of them parts of the capsule, which coated the hydrogel implant on the scleral surface. Some fragments were surrounded with a foreign body giant cell granulomatous reaction. Changes in scleral curvature and scleral thinning were consequences of the buckling procedure. The hydrogel fragmentation previously observed in experimental and human specimens gave histologic evidence of degradation of this material after its implantation on the eye surface. This characteristic demonstrates the instability of the material after implantation.

Adult↗

PubMed2000

Lymphoma classification--from controversy to consensus: the R.E.A.L. and WHO Classification of lymphoid neoplasms.

BACKGROUND: Controversy in lymphoma classification dates back to the first attempts to formulate such classifications. Over the years, much of this controversy arose from the assumption that there had to be a single guiding principle--a 'gold standard'--for classification, and from the existence of multiple different classifications. DESIGN: The International Lymphoma Study Group (I.L.S.G.) developed a consensus list of lymphoid neoplasms, which was published in 1994 as the 'Revised European-American Classification of Lymphoid Neoplasms' (R.E.A.L.). The classification is based on the principle that a classification is a list of 'real' disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features. The relative importance of each of these features varies among diseases, and there is no one 'gold standard'. In some tumors morphology is paramount, in others it is immunophenotype, a specific genetic abnormality, or clinical features. An international study of 1300 patients, supported by the San Salvatore Foundation, was conducted to determine whether the R.E.A.L. Classification could be used by expert pathologists and had clinical relevance. Since 1995, the European Association of Pathologists (EAHP) and the Society for Hematopathology (SH) have been developing a new World Health Organization (WHO) Classification of hematologic malignancies, using an updated R.E.A.L. Classification for lymphomas and applying the principles of the R.E.A.L. Classification to myeloid and histiocytic neoplasms. A Clinical Advisory Committee (CAC) was formed to ensure that the WHO Classification will be useful to clinicians. RESULTS: The International Lymphoma Study showed that the R.E.A.L. Classification could be used by pathologists, with inter-observer reproducibility better than for other classifications (> 85%). Immunophenotyping was helpful in some diagnoses, but not required for many others. New entities not specifically recognized in the Working Formulation accounted for 27% of the cases. Diseases that would have been lumped together as 'low grade' or 'intermediate/high grade' in the Working Formulation showed marked differences in survival, confirming that they need to be treated as distinct entities. Clinical features such as the International Prognostic Index were also important in determining patient outcome. The WHO Clinical Advisory Committee concluded that clinical groupings of lymphoid neoplasms was neither necessary nor desirable. Patient treatment is determined by the specific type of lymphoma, with the addition of grade within the tumor type, if applicable, and clinical prognostic factors such as the International Prognostic Index (IPI). CONCLUSIONS: The experience of developing the WHO Classification has produced a new and existing degree of cooperation and communication between oncologists and pathologists from around the world, which should facilitate progress in the understanding and treatment of hematologic malignancies.

Decision Making↗

PubMed2000

[LEEP versus cold knife conization for treatment of cervical intraepithelial neoplasias].

OBJECTIVE: This study was performed to evaluate the effectiveness and side effects of loop electrosurgical excision procedure (LEEP) in comparison to cold knife conization for the treatment of cervical intraepithelial neoplasia (CIN). MATERIAL AND METHODS: Between January 1996 and July 1998, 177 patients underwent conization. In a matched-pair setting, 50 cases with LEEP were compared with 100 classical conization cases. LEEP was performed with ectocervical and endocervical excision. RESULTS: Perioperative complications were less in the LEEP group (6% vs. 11%). The mean volume of LEEP specimens (1.6 cm3) was significantly smaller than the volume of cone specimens (2.6 cm3). Thermal artifacts were negligible. There were no significant differences in the proportion of margin involvement (20% vs. 19%) and residual/recurrent CIN. The endocervical excision contained dysplastic tissue in 38% of the cases; more important, a positive endocervical excision was found in 14/21 CIN 3 cases (67%). The success rate, was similar in both groups (96% vs. 97%). Hospitalization time was less for the LEEP group. CONCLUSIONS: LEEP conization is a safe and cost effective procedure with a lower complication rate providing a significantly smaller specimen compared to cold knife conization. Therefore, LEEP conization may substitute cold knife conization. However, we do recommend to perform LEEP conization with an endocervical excision to reduce residual CIN.

Adult↗

PubMed1999

Microsatellite instability and loss of heterozygosity in prostatic carcinomas: comparison of primary tumors, and of corresponding recurrences after androgen-deprivation therapy and lymph-node metastases.

BACKGROUND: The molecular mechanisms leading to prostate cancer progression are poorly understood. In particular, those changes which are responsible for androgen-independent growth and metastatic spread in prostate cancer are an issue of current investigations. METHODS: To gain more insight into these processes, paired microdissected samples from both untreated, locally advanced primary tumors (n = 20) and recurrences (n = 20) after conventional androgen-deprivation therapy (ADT) were analyzed retrospectively for microsatellite instability (MSI) and loss of heterozygosity (LOH) at nine loci on chromosomes 8, 18, and X by polymerase chain reaction. In parallel, 12 prostatic carcinomas treated by radical prostatectomy and nine corresponding lymph-node metastases were analyzed in the same way. RESULTS: The group treated with ADT showed a total of 10 MSI in 7 of the primary tumors (35%): 4 of these (20%) at one locus, and 3 of these (15%) at two loci. In the recurrences, MSI was observed in 4 cases (20%): 3 of these at one locus (15%), and 1 of these (5%) at two loci. LOH was found in 8 cases (40%) before as well as after ADT. In the radically resected carcinomas, MSI could be detected at two chromosomal loci in one of the primary tumors (8%) and in one of the metastases (11%); LOH was found in 2 primaries (16%) and 3 metastases (33%). CONCLUSIONS: Although MSI can be found in advanced prostatic carcinomas, it apparently does not play a major role in the progression of prostate cancer regarding androgen-independent growth or lymphogenous spread.

Aged↗