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J Thiele

Publications and source records attributed to J Thiele.

At least 19 recordsLinked to original sources
PubMed2006

Grade of bone marrow fibrosis is associated with relevant hematological findings-a clinicopathological study on 865 patients with chronic idiopathic myelofibrosis.

Controversy continues to exist regarding not only the exact definition and grading of myelofibrosis (MF), but also whether, and to what extent, this feature may be correlated with clinical findings. A retrospective study was performed involving 865 bone marrow (BM) biopsies together with the clinical records from patients with chronic idiopathic myelofibrosis (CIMF). Diagnosis was established according to the World Health Organization criteria, and assessment of MF followed a consensus scoring system that included four grades (MF-0 to MF-3). Histopathological and clinical evaluations were carried out in an independent fashion. Prefibrotic and early CIMF (MF-0/-1) were presented by 565 patients showing borderline to mild anemia and no or slight splenomegaly, but frequently, thrombocytosis exceeding 500x10(9)/l was shown. In 300 patients, manifest reticulin and collagen fibrosis (MF-2/-3) were characterized by marked anemia, gross splenomegaly, peripheral blasts, and normal to decreased platelet and leukocyte counts. The latter cohort was consistent with findings generally in keeping with MF with myeloid metaplasia. Regarding the stepwise evolution of disease, sequential BM examinations showed that in 103 patients, prefibrotic and early CIMF transformed into advanced stages accompanied by correspondingly developing clinical and histomorphological features. Survival analysis (univariate calculation) revealed a significantly more favorable prognosis in prefibrotic vs advanced stages of CIMF. On the other hand, higher classes of MF also exerted a higher clinical risk profile (Lille score). In conclusion, the dynamics of the disease process in CIMF are characterized by evolving MF in the BM and closely associated changes of relevant hematological findings.

Biopsy↗
PubMed2006

[Sebaceous glands as transporters of vitamin E].

Human sebum is produced by sebaceous glands and reaches the skin surface via secretion through the hair shaft. There is experimental evidence that the sebaceous glands and sebum serve as a transport mechanism taking the lipophilic antioxidant vitamin E from the blood to the skin surface. The highest levels of vitamin E are found in the sebum and in the skin lipid film in sebum-rich areas such as facial skin. Recent studies indicate that daily oral supplementation of moderate doses of alpha-tocopherol for at least 3 weeks leads to significant increases of vitamin E levels in human skin sites with a high density of sebaceous glands, such as the face. Thus, the potential photoprotective and antioxidants effects of oral vitamin E, as well as possibly other antioxidants, are site-dependent. These findings should be considered when designing clinical studies to assess the efficacy of oral antioxidants against oxidative stress in the skin.

Acne Vulgaris↗
PubMed2006

[Secondary malignancies after successful primary treatment of malignant Hodgkin's lymphoma].

Malignant Hodgkin's lymphoma (HL) has become a curable disease through the increasing intensity of the treatment strategies applied. These regimens are aggressive, including radiotherapy and chemotherapy leading to the possibility of secondary malignancies. The German Hodgkin Lymphoma Study Group considered three cohorts including 5,411 patients with all stages of HL. In 127 patients a secondary solid tumor was diagnosed (cumulative risk 2%, median follow-up 72 months), with bronchial carcinomas (23.6%) and colorectal adenocarcinomas (20.5%) being the most frequent neoplasms. Secondary acute myeloid leukemia was found in 36 patients, another ten developed myeloid dysplasia (cumulative risk 1%, median follow-up 55 months). A total of 52 patients revealed a non-Hodgkin's lymphoma (NHL; cumulative risk 0.9%, median follow-up 46 months). The overall incidence of secondary malignancies was 3.9% in patients who had been treated successfully for their HL with radio- and/or chemotherapy.A secondary NHL can be particularly difficult to be distinguished from the preceding HL. Therefore, in case of a suspected relapse, a complete histopathological work-up must be performed.

Antineoplastic Agents↗
PubMed2006

Bone marrow histopathology in the diagnosis of chronic myeloproliferative disorders: a forgotten pearl.

Histopathology of bone marrow (BM) biopsies plays a crucial role in the interdisciplinary approach to diagnosis and classification of chronic myeloproliferative disorders (CMPDs). Based on careful clinicopathologic studies, BM features are critical determinants that help to predict overall prognosis, to detect complications such as progression to myelofibrosis and blast crisis, and to assess therapy-related changes. A systematic evaluation of BM histopathology allows an objective identification of cases of (true) essential thrombocythemia (ET) and their separation from (false) ET, which often is the prodromal stage of chronic idiopathic myelofibrosis (CIMF). By follow-up examinations that include BM biopsies, the progression of the disease process is unveiled, which is especially important for patients with initial (early) polycythemia vera and prefibrotic CIMF that may require a different therapeutic approach than the full-blown stages. In conclusion, BM biopsy should be considered as major diagnostic tool for evaluation and follow-up of patients enrolled in prospective studies.

Bone Marrow↗
PubMed2006

[A 29-year-old man with Takayasu's arteritis].

We report on a 29-year-old male patient with collapse and recurrent vertigo. Physical examination showed a bruit of the left common carotid artery on auscultation and a pulselessness of both arms. The diagnosis of Takayasu's arteritis was based on the results of duplex sonography, MRI and angiography (stenosis and occlusion of extracranial arteries). Laboratory results did not reveal any specific changes. Combined treatment with prednisolone and azathioprine was initiated. After 12 days we saw an improvement of duplexsonographical and laboratory findings. Takayasu's disease should be considered as a differential diagnosis in patients with stenosis and occlusions of the aortic arch and its main branches (e.g. pulselessness). MRI is a valuable method in detection of wall abnormalities of the aorta, its branches and other large arteries.

Adult↗
PubMed2006

Morphology of the bone marrow after stem cell transplantation.

In many haematological conditions the only curative option is stem cell (SCT) or bone marrow (BM) transplantation. Little information exists about BM morphology following non-ablative engraftment. During the pretransplantation period and depending on the kind of pretreatment, there may be hypoplasia, residual disease and varying degrees of fibrosis. In the post-transplantation period, after 1-3 weeks of transfusion-dependent pancytopenia, the first signs of successful engraftment are indicated by the recurrence of neutrophils, monocytes and erythrocytes in the peripheral blood. In the BM there is slow regeneration of erythropoiesis, followed by the other lineages of haematopoiesis and increase in reticulin fibres or even a resolution of fibrosis. Diagnostic problems arise when neoplastic lympho- or haematopoiesis are maintained following transplantation. Moreover, there may be a significant graft versus tumour response reaction or an already relapsing disease needing aggressive treatment. On the other hand, a conspicuous dyshaematopoiesis should not be mistaken as representing a myelodysplastic syndrome. The presence of granulomas being treatment-related or a manifestation of intercurrent granulomatous disease has to be considered. More advanced knowledge of the histological features of regenerating BM will certainly aid the recognition of relapsing disease and is needed for the adequate reporting of post-transplant alterations associated with a successful or failing engraftment.

Bone Marrow↗
PubMed2006

Trisomy 8 in prefibrotic early stages of chronic idiopathic myelofibrosis: a fluorescence in situ study of bone marrow biopsies.

Repeatedly performed bone marrow biopsies were studied in 30 patients with chronic idiopathic myelofibrosis (CIMF) by fluorescence in situ hybridization to detect and quantify trisomy 8 anomaly during the evolution of disease. For the establishment of threshold values we used negative and positive control specimens. At least 500 cells were evaluated in each specimen and only nuclei with three distinctive signals were regarded as positive. According to the controls, 27 patients revealed false-positive signals ranging from 0 to 1.2% (0.88 +/- 1.12). On the other hand, 3 patients showed an incidence of more than 6.5% (up to 10.1%) in the initial prefibrotic as well as advanced fibro-osteosclerotic stages of CIMF. In conclusion, trisomy 8 has been demonstrated already in the prodromal stages of CIMF and therefore is not limited to classical fibro-osteosclerotic manifestations.

Biopsy↗
PubMed2006

Myelofibrosis in chronic myeloproliferative disorders--dynamics and clinical impact.

In chronic myeloproliferative disorders, presenting or evolving myelofibrosis (MF) is associated with significant morbidity and mortality. A systematically conducted evaluation of previous studies and data from our own material reveals a strikingly expressed heterogeneity of findings. Assessment of MF should be performed by a recently established semiquantitative scoring system regarding quantity and quality (reticulin versus collagen). It is important to differentiate between a fiber increase in bone marrow specimens and the clinical diagnosis that is explicitly based on extramedullary hematopoiesis (myeloid metaplasia). For this reason, prodromal stages of (reticulin) fibrosis are overlooked by the clinicians. Up to 30% of patients with chronic myelogenous leukemia show a minimal to advanced MF that is significantly associated not only with corresponding clinical parameters but more importantly with prognosis. In polycythemia vera about 20% of patients may display some degree of reticulin fibrosis at diagnosis, depending on stage of the disease. Transformation into (collagen) MF after more than 10 years is accompanied by clinical signs of myeloid metaplasia (spent phase). Essential thrombocythemia (ET) is characterised by the absence of increased reticulin at onset and an insignificant progression into MF, provided diagnosis is performed by the WHO criteria. Discrimination of prefibrotic and early stages of chronic idiopathic myelofibrosis (CIMF) from ET is relevant, especially concerning the rate and time usually required for the development of MF with myeloid metaplasia (full-blown CIMF). In conclusion, more elaborate evaluations including standardized grading of MF is warranted by regarding bone marrow biopsy specimens in association with clinical parameters including follow-up examinations.

Bone Marrow Examination↗
PubMed2006

Lewis(y) antigen (CD174) and apoptosis in gastric and colorectal carcinomas: correlations with clinical and prognostic parameters.

Lewis(y) (Le(y)), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Le(y) expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Le(y) and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Le(y) reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Le(y) expression compared to other tumor types. In colorectal cancers, Le(y) was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Le(y) antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data.

Adenocarcinoma↗
PubMed2005

Bone marrow changes in chronic myelogenous leukaemia after long-term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients.

AIMS: To carry out an immunohistochemical study on bone marrow (BM) biopsy specimens in 75 patients with chronic myelogenous leukaemia (CML) on long-term STI571 therapy. METHODS AND RESULTS: Sequential BM specimens taken at intervals of 21 +/- 6 months were investigated by enzyme- and immunohistochemistry including proliferating cell nuclear antigen and apoptosis. Evaluation was performed either by semiquantitative scoring or by morphometry (CD61+ megakaryopoiesis). In 41 patients with chronic phase CML, treatment resulted in a significant decrease in cellularity and neutrophil granulopoiesis contrasting with an accumulation of erythroid precursor cells. Morphometry showed a reduction of abnormal micromegakaryocytes consistent with normalization. Regression of myelofibrosis was identified in eight of 15 patients, whereas progression occurred in 17 patients; mostly in those with acceleration and blastic crisis. The increased post-treatment incidence of reactive lymphoid nodules was remarkable. Myeloblasts, CD34+ progenitors and immature myelomonocytic cells initially decreased, but recurred in 14 patients who later developed a relapse. STI571 exerted an inhibitory effect on cell proliferation associated with enhanced apoptosis in responding patients. CONCLUSION: Long-term treatment with STI571 exerts pronounced changes on BM histopathology that not only involve haematopoiesis and stromal constituents, but also proliferation and apoptosis.

Antigens, CD34↗
PubMed2005

Anagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea.

A comparative immunohistochemical and morphometric study was performed on megakaryocytes in 20 patients presenting with initial-early stage chronic idiopathic myelofibrosis and accompanying thrombocythemia to elucidate histological features developing after hydroxyurea (HU) versus anagrelide (ANA) therapy. Representative pre-and posttreatment bone marrow biopsies were involved including the monoclonal antibody CD61 for the identification of precursor and mature stages of megakaryopoiesis. An elaborate morphometric evaluation was in keeping with a left-shifting showing a more frequent occurrence of promegakaryoblasts and microforms in both therapy groups. However, contrasting ANA, HU generated defects of differentiation consistent with significant dysplastic changes. In conclusion, concern about a possible leukemogenic capacity following long-term HU therapy is supported by our findings.

Antineoplastic Agents↗
PubMed2005

Diagnostic impact of bone marrow histopathology in polycythemia vera (PV).

The criteria of the Polycythemia Vera Study Group (PVSG), although acknowledged as the gold standard to establish the diagnosis of polycythemia vera (PV), do not regard bone marrow (BM) histopathology. Arguments include the existence of sufficient objective markers of disease and the lack of independently performed morphological studies or standardized criteria. The aim of this review is to evaluate morphological characteristics of erythrocytosis and to determine whether distinctive patterns of histopathology exist. A review of the pertinent literature and evaluation of 334 patients from our files with a borderline to marked increase in hemoglobin was performed. In extension to former descriptions of BM features by the PVSG, a tri-lineage myeloproliferation (panmyelosis) with a pleomorphous appearance of megakaryopoiesis revealed that, besides increase in size, there was a lack of gross cytological anomalies. Differentiation from secondary polycythemia (SP) was accomplished by regarding these features and the conspicuously expressed stromal changes (plasmacytosis, eosinophils, cell debris and iron deposits). In about 96% of this cohort a clear-cut separation from SP was achieved, even in the initial (latent) stages. When accompanied by an elevated platelet count, these precursor stages may clinically mimick essential thrombocythemia because they are not recognized by the conventional criteria. Advanced stages (spent phases) of PV were consistent with an increased left-shifted granulocytic proliferation, accompanied by reduction of erythroid precursors and progressive myelofibrosis (post-polycythemic myeloid metaplasia). Finally, an increase in dysplastic changes and immaturity signalled a transition into blastic crisis. In conclusion, PV is characterized by a distinctive pattern of histopathology that has been gained in an independent and blind fashion and therefore, dissolves arguments about failing specificity.

Animals↗
PubMed2005

Standardization of bone marrow features--does it work in hematopathology for histological discrimination of different disease patterns?

Standardized bone marrow (BM) features determined by semiquantitative scoring are valuable tools for the recognition and easily reproducible interpretation of histological patterns in hematopathology. This procedure may help to characterize various disease entities, but especially to differentiate chronic myeloproliferative disorders (MPDs) with increased platelet counts from reactive thrombocytosis (RTh). A clear-cut separation of these conditions continues to present a major problem in hematology. Therefore MPDs are a most suitable model to test the diagnostic relevance of this procedure. By regarding the literature and based on archive material that involved BM biopsies of 319 patients, a semiquantitative grading of histological parameters was performed. Standardized features were applied for a stepwise discriminant analysis to establish different sets of variables exerting a diagnostic impact. A distinction into five histological patterns was achieved that showed a correctly predicted group membership of about 94 %. These were consistent with the clinicopathological diagnosis of polycythemia vera, essential thrombocythemia (ET), prefibrotic or early fibrotic chronic idiopathic myelofibrosis (CIMF) and finally RTh. Variables of discriminating potency according to their ranking included megakaryopoiesis (maturation defects, nuclear lobulation, naked and bulbous nuclei, small and giant size), reticulin fibers, erythro- and granulopoiesis (left shifting and quantity) and cellularity. These findings are in keeping with the assumption that characteristic patterns of BM histopathology can be assigned to different subtypes of MDPs mimicking ET. Discrimination between ET and especially early stage CIMF with thrombocythemia is warranted because of significant implications concerning therapeutic strategies, follow-up examinations and survival. Regarding these results, a schematic procedure is proposed to be used for daily routine diagnosis concerning the discrimination of MPDs.

Bone Marrow↗
PubMed2005

Dynamics of bone marrow changes in patients with chronic idiopathic myelofibrosis following allogeneic stem cell transplantation.

Scant knowledge exists about the dynamics of fibro-osteosclerotic bone marrow (BM) lesions and regeneration of hematopoiesis following allogeneic peripheral stem cell transplantation (SCT) in chronic idiopathic myelofibrosis. Therefore, an immunohistochemical and morphometric study was performed on BM biopsies in 20 patients before and at standardized intervals (days 30 through 384) following SCT. In responding patients, a total regression of the pretransplant increased fibrosis was completed in the posttransplant period after about six months, while the extent of osteosclerosis did not change significantly during observation time. The quantity of CD61+ megakaryocytes including precursors was strikingly variable after SCT and, by using planimetric methods, atypical microforms exhibiting a dysplastic aspect could be demonstrated. These anomalies may be responsible for posttransplant thrombocytopenia. CD34+ progenitor cells were increased before transplantation, however, their number declined rapidly to normal values in responding patients. Nucleated erythroid precursors revealed a decreased amount before and after SCT accounting for anemia. Large clusters of this cell lineage indicated an initial hematopoietic reconstitution comparable with the expansion of the neutrophil granulopoiesis. Proliferative activity and apoptosis showed an increase until one year after SCT that implied a still regenerating hematopoiesis in keeping with an enhanced cell turnover.

Adolescent↗
PubMed2004

Acute panmyelosis with myelofibrosis: a clinicopathological study on 46 patients including histochemistry of bone marrow biopsies and follow-up.

Controversy continues whether acute panmyelosis with myelofibrosis (APMF) exists as a well-defined clinicopathological entity. Following exclusion of overt acute myeloid leukemia (AML), especially the megakaryoblastic subtype, a retrospective study was performed on 46 patients with clinical and morphological features suggesting the diagnosis of APMF. All patients had a bone marrow (BM) biopsy performed at onset, and 13 had follow-up examinations. Enzyme histochemical and immunohistochemical techniques were applied and BM features evaluated by a semiquantitative scoring system. Clinical findings consisted of pancytopenia associated with a left-shifted differential count of the peripheral blood (less than 5% blasts) and no or minor splenomegaly. During follow-up (median survival 9 months) 35 patients developed severe BM insufficiency and 10 transformed into overt AML. Although myelofibrosis was a characteristic finding, other BM features proved to be heterogeneous. Cellularity was reduced in 13 and increased in 25 specimens. Most prominent was a left-shifted, often macrocytic erythropoiesis and a maturation defect of the neutrophil series. In 15 patients an increase (less than 20%) in CD34+ progenitors, immature myelomonocytic cells, and megakaryoblasts was noted. Abnormalities of megakaryocytes (atypical microforms, clustering, dysplasia) were regularly present. The stroma showed an inflammatory reaction (perivascular plasmacytosis, lymphoid nodules, many macrophages, iron deposits) in about 50% of the samples. Sequential BM biopsies revealed an accumulation of lysozyme-expressing myelomonocytic and CD34+ progenitor cells suggesting an increase in blasts. In conclusion, APMF may not be a distinct entity, but includes hyperfibrotic myelodysplastic syndromes (MDS) either primary or secondary, a rare form of initial AML with fibrosis, and even cases of toxic myelopathy.

Acute Disease↗
PubMed2004

[Therapy-related changes of angiogenesis in Philadelphia chromosome positive chronic myelogenous leukemia].

To elucidate the effect of first-line treatment with interferon (IFN), hydroxyurea (HU) and the tyrosine kinase inhibitor imatinib (STI571) on angiogenesis, we studied bone marrow (BM) biopsies in 104 patients with chronic myelogenous leukemia (CML) and 138 patients before and after allogeneic BM transplantation (BMT). After immunostaining (CD34) and morphometric analysis in comparison with a control group, CML specimens showed an increased vascularity and conspicuous morphological abnormalities of microvessels. A close relationship between microvessels and fiber density was detectable in initial biopsies and also in repeatedly performed examinations following therapy. Monotherapy by imatinib and HU generated a significant reduction of microvessels and reticulin fibers in contrast to changes after IFN administration or combination regimens of IFN and HU. A persistence of numerical and structural anomalies of vasculature was observable even several months after BMT. These anomalies shed some light on disturbances of the stroma compartment after myeloablative therapy. The relationship between BM vascularity and fibers is probably dependent on concomitant changes of megakaryopoiesis as the source of various mediators involved in the development of myelofibrosis and neo-angiogenesis acting within a complex functional network.

Antineoplastic Agents↗
PubMed2004

[Regression of oesophageal carcinomas after neoadjuvant radiochemotherapy: criteria of the histopathological evaluation].

Following surgical resection locally advanced oesophageal carcinomas exhibit a bad prognosis and therefore neoadjuvant therapeutic strategies were developed. Because success of therapy is associated with the extent of tumor regression in this context, the introduction of objective histopathological criteria seems to be very important. This study included 67 patients with oesophageal carcinomas (cT2-cT4 cNx cM0) that were treated with a cisplatin- and 5-fluorouracil-containing simultaneous radiochemotherapy. In 43 patients squamous cell, in 24 cases adenocarcinomas were diagnosed. After completion of therapy, a surgical resection and a histopathological examination of the tissue specimens were performed. The extent of tumor regression was histologically evaluated and therapy-induced alterations were graded semiquantitatively. Thereby, a significantly favorable prognosis was observed in the group of patients that showed a regression of carcinomas of 90% or more. Additionally, the extent of a resorptive-histiocytic reaction, giant cells and lymphocytic infiltrates correlated with the grade of regression. These results underline the importance of an exact examination and histomorphological evaluation of the response for the assessment of survival probability after neoadjuvant radiochemotherapy of oesophageal carcinomas.

Antineoplastic Combined Chemotherapy Protocols↗