Personal life and working conditions of trainees and young specialists in clinical microbiology and infectious diseases in Europe: a questionnaire survey.

The purpose of this investigation was to assess the balance between the personal and professional lives of trainees and young European specialists in clinical microbiology (CM) and infectious diseases (ID), and determine differences according to gender, country of training, workplace and specialty. The Steering Committee of the Trainee Association of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) devised a questionnaire survey consisting, beyond the demographic questions, of nine yes/no questions, 11 Likert scale self-evaluations and one open-response item on parenthood, working conditions, quality of life, alcohol consumption and burnout. This anonymous survey in English was held between April and July 2015 among European CM/ID trainees and young specialists (<3 years after training completion). Responses from 416 participants with a mean age of 32 years [standard deviation (SD) 5 years] were analysed. Females and physicians from Northern/Western Europe (NWE) benefit more from paternity/maternity leaves even during training than their counterparts. Among all respondents, only half of breastfeeding mothers enjoyed the benefit of working hours flexibility. Only two-thirds of respondents found their working environment stimulating. In comparison to colleagues from other parts of Europe, trainees and young specialists from Southern/Eastern Europe (SEE) had less frequent regular meetings with mentors/supervisors and head of departments where trainees' issues are discussed. Also, physicians from SEE were more frequently victims of workplace mobbing/bullying in comparison to those from other regions. Finally, multivariate analysis showed that female gender, SEE region and ID specialty were associated with burnout feelings. Female gender and country of work from SEE largely determine satisfactory working conditions, the possibility of parenthood leaves, amount of leisure time, mobbing experiences and burnout feelings among European CM/ID trainees and young specialists.

A large survey among European trainees in clinical microbiology and infectious disease on training systems and training adequacy: identifying the gaps and suggesting improvements.

The purpose of this investigation was to perform a survey among European clinical microbiology (CM) and infectious disease (ID) trainees on training satisfaction, training tools, and competency assessment. An online, anonymous survey in the English language was carried out between April and July 2015. There were 25 questions: seven in a 5-point Likert scale (1: worst scenario, 5: best scenario) and the remainder as closed multiple-choice questions in five areas (satisfaction, adequacy, system, mentorship, and evaluation of training). Included were 419 respondents (215 CM, 159 ID, and 45 combined CM/ID) from 31 European countries [mean age (standard deviation) 32.4 (5.3) years, 65.9 % women]. Regarding satisfaction on the training scheme, CM and ID scored 3.6 (0.9) and 3.2 (1.0), respectively. These scores varied between countries, ranging from 2.5 (1.0) for Italian ID to 4.3 (0.8) for Danish CM trainees. The majority of respondents considered training in management and health economics inadequate and e-learning and continuing medical education programs insufficient. Many trainees (65.3 % of CM and 62.9 % of ID) would like to have more opportunities to spend a part of their training abroad and expected their mentor to be more involved in helping with future career plans (63.5 % of CM and 53.4 % of ID) and practical skills (53.0 % of CM and 61.2 % of ID). Two-thirds of the respondents across the specialties agreed that a European exam should be developed, but half of them thought it should not be made mandatory. This survey shows high heterogeneity in training conditions in European countries, identifies perceived gaps in training, and suggests areas for improvements.

[Primary Hodgkin lymphoma of the stomach--a case report]. / Hodgkinuv lymfom zaludku--kazuistika.

A case of a 69-year-old male with a one-month history or recurrent attacks of GI bleeding, secondary anemic syndrome and epigastric pain is reported. Endoscopic examination revealed a tumorous lesion suspicious of malignancy. Neither lymphadenopathy nor any other tumorous lesion was identified by extensive clinical examination. In the biopsy specimens there was ulcerated gastric mucosa with an infiltration by lymphoid cells, predominantly of mature T-cell type. Atypical large cells with large nuclei with prominent nucleoli were dispersed among the mature lymphocytes. These atypical cells were both mono- and binucleated (Hodgkin and RS cells). Both cell types revealed immunohistochemically membranous and dot-like perinuclear positivity of CD30 and CD15 antigens. Based on morphologic features and immunohistochemical findings, a diagnosis of primary gastric Hodgkin lymphoma was established. Diagnostic approach, as well as differential diagnosis of primary Hodgkin lymphoma in this extremely rare location, are discussed.

[Isolated lymphadenopathy as the first presentation of systemic mastocytosis--description of two cases]. / Izolovaná lymfadenopatie jako první projev systémové mastocytózy--popis dvou prípadu.

Presented are two cases of systemic mastocytosis in 46- and 63-year-old women, where the correct diagnosis was established in randomly disclosed cervical respectively intraabdominal lymphadenopathy. Both cases lacked characteristic skin and systemic mast-cell mediator symptoms at the time of histologic diagnosis. The first case was classified as a indolent systemic mastocytosis without any proven genetic alteration, the second one met the criteria of aggressive systemic mastocytosis with eosinophilia, where the point mutation asp816val in c-kit gene was confirmed and the patient responded unexpectedly well to Gleevec. Discussed are both conventional morphological differential diagnosis of mastocytosis in lymph nodes and recent advances in genetics of these systemic clonal mast cell proliferations. The latter not only outlines the oncopathogenesis but, in particular, also provides important prognostic and biological implications of this peculiar disease.

[Bone marrow fibrosis during therapy of hairy cell leukemia]. / Fibróza kostní drene behem terapie vlasatobunecné leukémie.

The influence of Cladribin therapy to bone marrow fibrosis in patients with hairy cell leukemia was studied. Eighteen patients were included in the study; bone marrow fibrosis was graded 0-4 according to the quantity and pattern of distribution of reticulin. The grade of bone marrow fibrosis was established before the therapy and then in 12- and 24-month intervals. Patients showed complete remission after the therapy and remarkable reduction of bone marrow fibrosis.

Effect of 2-chlorodeoxyadenosine therapy on bone marrow fibrosis in hairy cell leukemia.

The study shows the influence of 2-chlorodeoxyadenosine therapy on bone marrow fibrosis in patients with hairy cell leukemia. Eighteen patients were studied; bone marrow fibrosis was graded 0-4 according to the quantity and pattern of distribution of reticulin. The grade of bone marrow fibrosis was established before the therapy and then in 12- and 24-month intervals. Patients showed complete remission after the therapy and remarkable reduction of bone marrow fibrosis.

[Complete regression of bone marrow fibrosis following allogeneic peripheral blood stem cell transplantation in a patient with idiopathic myelofibrosis]. / Kompletní regrese fibrózy kostní drene po alogenní transplantaci periferních krvetvorných bunek u pacienta s idiopatickou myelofibrózou.

The authors present a case of a 47-year-old man with idiopathic myelofibrosis. The diagnosis of myelofibrosis was made in 1981. Because of progression of the disease and failure of hematopoiesis in 2002, allogeneic peripheral blood stem cell transplantation was performed; the donor was an HLA identical relative. Six months after transplantation, trephin biopsies were made and a complete regression of bone marrow fibrosis was documented. It is the first case of this treatment for idiopathic myelofibrosis in the University Hospital in Hradec Králové.

[Immunohistochemical detection and quantification of minimal residual disease using DBA.44 antibodies in trephination biopsies of hairy cell leukemia]. / Imunohistochemická detekce a kvantifikace minimální reziduální nemoci pomocí protilátky DBA.44 v trepanobiopsiích pacientu s vlasatobunecnou leukémií.

Hairy cell leukemia patients treated with 2-chlorodeoxyadenosine or 2-deoxycoformicin achieve a very high number of therapeutic responses. After complete remission, i.e. minimal residual disease, we cannot demonstrate the disease activity, splenomegaly, or lymphadenopathy; moreover, there comes to normalization of hemoglobin concentration, leukocyte count, and platelet count. No leukemic cells in peripheral blood or bone marrow smears can be seen with the use of staining techniques. They can be demonstrated immunohistochemically in decalcified trephine bone marrow biopsies with the use of DBA.44 antibody together with their morphologic features. For quantification of leukemic cells we use LUCIA-M image analysis.

[Hairy-cell leukemia]. / Vlasatobunecná leukémie.

Presented is on overview of hairy cell leukemia problems in diagnostics. Methods of diagnosis--both clinical (clinical course, laboratory findings) and histopathologic are described in detail. There are also immunophenotypic findings described. Furthermore, differential diagnosis together with therapeutic methods, and the prognosis of the disease are depicted, too.

Composite tumor consisting of dermatofibrosarcoma protuberans and giant cell fibroblastoma associated with intratumoral endometriosis. Report of a case.

We present a unique case of composite skin tumor of the vulva consisting of dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) with an intratumoral focus of endometriosis. A 31-year-old female with a 10-year-history of a recurring subcutaneous tumor in the vulvar area underwent excision of the seventh recurrence of the tumor. Microscopic examination revealed a composite fibrohistiocytic tumor consisting of DFSP and GCF. Additionally, a focus of endometriosis within the tumor tissue was found. Malignant transformation of extragonadal endometriosis has already been described; we present, however, the occurrence of a focus of endometriosis within the tissue of a hormonally independent soft tissue tumor. There is a possible link to the occurrence of cutaneous endometriosis at previous surgery sites and in the scars. The presence of endometriosis within the soft tissue tumor represents, to the best of our knowledge, a previously undescribed collision phenomenon.

The degree of bone marrow infiltration in patients with hairy cell leukemia treated with splenectomy compatible with long-term hematological remission.

To determine the degree of bone marrow infiltration with hairy cells which is compatible with long-term hematological remission in patients treated with splenectomy, we have investigated 7 patients surviving in hematological remission 61 to 255 months (median 184 months) after splenectomy. As hematological remission has been considered absence of hairy cells (HCs) in the peripheral blood, normalization of peripheral blood cell counts (hemoglobin 120 g/l, white cell count 4.0 x 10(9)/l, absolute granulocyte count 1.5 x 10(9)/l, platelet count 100 x 10(9)/l) and absence of lymfadenopathy and any other activity of the disease. For detection of HCs a very sensitive method of immunostaining with monoclonal antibody DBA.44 in our own modification has been used. Low values of sIL-2R which is considered to be a non invasive marker of tumor burden and activity in HCL were in agreement with the opinion that the bone marrow was the only locality of tumor involvement in splenectomized patients. Infiltration up to 20% with HCs (range 4% to 20%, median 10%) was found to be compatible with long-term hematological remission and long-term overall survival. Patient (No 1) with 30% infiltration of bone marrow with HCs, still normal peripheral blood cell counts, but a very high level of sIL-2R represents extraordinary finding which has been discussed in details.

Differential expression of the Ca2+ binding S100A6 protein in normal, preneoplastic and neoplastic colon mucosa.

The expression of calcium-binding protein S100A6 was investigated in normal colon tissue, in colon adenomas and in colorectal carcinomas. Using an immunoblotting approach we detected four S100A6 variants with Mwt of 10 kDa and pI of 5.05 (isoform I), 5.15 (isoform II), 5.23 (isoform III) and 5.32 (isoform IV) that were differentially expressed in the analysed samples. The quantitative examination of S100A6 variant expression in 25 pairs of colorectal carcinoma and matched control mucosa proved a statistically significant increased abundance of S100A6 isoforms I (P = 0.004) and III (P = 0.025) in malignant tissue, and conversely, an increased level of S100A6 isoform IV in healthy tissue (P = 0.022). The expression of isoforms I and III and the loss of isoform IV were also observed in colon cancer cell lines. In addition, the immunohistochemical study of 16 primary colorectal carcinomas revealed both in the non-paired Student t-test and in the Mann Whitney test the statistically significant accumulation of S100A6 protein (P < 0.001) in the invasive margin of the tumour. The immunohistochemical analysis of S100A6 protein in polyps differing in clinical severity gave a strong staining that was maximal in dysplastic lesions. Thus, our results indicate a possible, statistically significant correlation (non-paired Student t-test P = 0.036) between S100A6 expression and colon carcinoma progression.

[Monitoring minimal residual disease in patients with hairy cell leukemia in complete remission after treatment with 2-chlorodioxyadenosine]. / Sledování minimální reziduální nemoci u nemocných s vlasatobunecnou leukémií v kompletní remisi po terapii 2-chlorodeoxyadenosinem.

Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA) induces in 85% patients complete remission. Complete remission is defined as the condition when signs of activity of the disease are absent, splenomegaly and lymphadenopathy are absent, the hemoglobin concentration is > or = 120 g/l, the absolute number of granulocytes is > or = 1.5 x 10(9)/l and the number of thrombocytes is > or = 100 x 10(9)/l. In complete remission in the peripheral blood, bone marrow aspirate and bioptic samples obtained by trephin bone marrow core biopsy, using standard staining (hematoxylin-eosin and May-Grünwald-Giemsa's method), no leukemic cells are present. When more sensitive methods are used (immunophenotyping, immunohistochemistry or molecular genetic methods), a persisting leukemic population can be detected which is described as minimal residual disease (MRD). For detection of MRD the authors used immunohistochemical examination of bone marrow with DBA.44 antibodies. As leukemic cells they described those which produced intense cytoplasmic and membrane positivity with antibody DBA.44 and corresponded morphologically to hairy cells. For evaluation computer analysis of the picture LUCIA-M was used. The infiltration grade was examined on three areas of standard size (3 x 65,265 micron 2) and expressed in percent. A total of 45 trepanobioptic specimens from 21 patients were examined who achieved after treatment with 2-CdA complete remission. In all samples suitable for evaluation the presence of leukemic cells (MRD) was detected with a median of 3% and a range of 1% to 18%. With induction of complete remission correlates also the low serum level of the soluble receptor for IL-2 (sIL-2R). In a female patient after 24 months of treatment with 2-CdA the grade of leukemic infiltration rose from 1% to 12% and during the 36th month to 50% DBA.44+ leukemic cells. The incipient relapse in this patient was not associated, despite marked infiltration of bone marrow, with failure of hematopoiesis and a marked rise of sIL-2R.

Protein abundance alterations in matched sets of macroscopically normal colon mucosa and colorectal carcinoma.

Our current results, aimed at the detection of protein abundance alterations that could be associated with the process of colon tumorigenesis, are summarized. The matched sets of macroscopically normal colon mucosa and colorectal carcinoma were examined by a one- or two-dimensional electrophoretic approach and proteins were identified using immunoblotting or mass spectrometry. The following results were observed: The levels of liver fatty acid-binding protein, actin-binding protein/smooth muscle protein 22-alpha and cyclooxygenase 2 were downregulated in colorectal carcinoma compared to normal colon mucosa. Conversely, the expression of a novel variant of heat shock protein70 and several members of the S100 protein family of calcium-binding proteins (two isoforms of S100A9, S100A8, S100A11 and S100A6) were upregulated in transformed colon mucosa. Despite the variations of the levels of expression of given protein among analyzed samples, all quantitative changes were found to be statistically significant (Mann-Whitney test assuming p < or = 0.05). We conclude that the proteomic approach is useful for the study of complex biological events underlying the process of colorectal tumorigenesis.

The analysis of S100A9 and S100A8 expression in matched sets of macroscopically normal colon mucosa and colorectal carcinoma: the S100A9 and S100A8 positive cells underlie and invade tumor mass.

The expression of calcium-binding protein S100A9 was investigated in 23 matched sets of colorectal carcinoma and normal colon mucosa using two-dimensional gel electrophoresis. We found that, from a group of 23 patients, the level of S100A9 protein, in comparison with matched normal colon mucosa, was significantly increased in malignant tissues of 16 patients (70%). Furthermore, an additional protein, identified by matrix-assisted laser desorption/ionization - mass spectrometry (MALDI-MS) as S100A8, exhibited an increased expression in the same specimens of malignant tissues as the S100A9 protein. The immunohistological analysis revealed the accumulation of S100A9 positive cells, macrophages and polymorphonuclear leukocytes along the invasive margin of colorectal carcinoma. The S100A8 protein was found to be produced in the same location. The possible participation of both proteins and, especially, its heterodimeric complex calprotectin in colorectal carcinoma regression could be taken into account.

[Gastrointestinal stromal tumor--GIST--case report]. / Gastrointestinální stromální tumor--GIST--kazuistika.

Authors describe a newly introduced oncological entity that represents different views on some already well known mesenchymal and neuroectodermal tumours of gastrointestinal tract. These submucosal GIT tumours, showing only few differences in both the clinical and histological pictures, are generally called gastrointestinal stromal tumours. This paper presents a case of 37 year old patient with this disease.

Minimal residual disease, its detection and significance in hairy-cell leukemia.

As minimal residual disease (MRD) is considered the detection of hairy cells (HCs) in a patient with hairy cell leukemia (HCL) in complete remission with the absence of detectable HCs by routine morphology of peripheral blood, aspirates and bone marrow core sections, using more sensitive methods of identification as immunohistological staining or polymerase chain reaction (PCR) to detect immunoglobulin heavy chain genes rearrangement. Various monoclonal antibodies (MoAbs) as CD20, DBA.44, B ly-7, HC2, CD25 and CD11c have been applied using immunological staining. There is no standardized technique for identification of MRD. According to the technique used the MRD has been detected in 13% to 100% of patients in complete remission (CR). It may be concluded that many patients, if not all, in stable CR may have residual HCs. Whether MRD will have impact on early relapse or on long term outcome, or whether patients in CR with persistent MRD will remain so, is a matter of a longer follow-up.

[Pathology on the Internet]. / Patologie v síti Internet.

Authors' experience gained during a one year usage of the Internet is presented. By now we have found many useful information resources related to the field of pathology. The MEDLINE database is available free of charge at several web sites as well as teaching diagnostic seminars, electronic color atlases, medical publishers homepages, etc. There is also a possibility to enter various topic-related groups in the framework of Internet discussion groups. The limiting factors for reaching medical information from the Internet is hardware and software equipment, the cost of Internet connection, and the data transmission capacity of phone lines.

[Synovial metaplasia around breast implants]. / Synoviální metaplazie kolem mamárních implantátu.

Three cases of the periprosthetic breast capsules showing typical features of synovial metaplasia are presented. The histological picture is characterized by the presence of cellular layer mimicking synovial membrane. These elements are devoid of basement membrane, otherwise, nevertheless, they strongly resemble single- or multilayered epithelium. Focally, the differentiation towards giant multinucleated cells is noted. Immunohistochemical profile, as well as the ultrastructure of the cells, confirms their histiocytic origin with advanced differentiation towards elements of the synovial membrane. These histological features are referred to as synovial or synovial-like metaplasia. They are found in considerable fraction of textured breast implant capsules. The pathogenesis remains uncertain; however, similar picture was observed in other locations in association with prolonged or repeated action of mechanical forces. Thus, movement of the implant in situ is the most probable trigger of synovial metaplasia.