Air spaces of the temporal bone: a morphometric analysis with clinical implications.

BACKGROUND: The main objective of the present study was to analyse the morphological variations of the air spaces of the temporal bone, that is, the pneumatized and air-filled spaces of the temporal bone cavities. MATERIALS AND METHODS: A total of 99 sides were analysed. Temporal bone pneumatic spaces (TBPS) were defined as the free spaces inside the cavities of the temporal bone filled with air, excluding the volume of the structures present in the investigated region. Total volumes of TBPS were calculated as the sum of total volumes of mastoid air cells (MAC), tympanic cavity (TC), and external auditory canal (EAC). Analyses were performed considering the general population and the female and male subgroups. RESULTS: The overall results obtained on Polish population were set as follows: the median total volume of TBPS was demonstrated at 7882.58 mm3 (lower quartile [LQ]: 6200.56 mm3; higher quartile [HQ]: 10393.16 mm3). The median volume of MAC was set at 5813.05 mm3 (LQ: 4224.94 mm3; HQ: 8181.81 mm3). The median of the total volume of the EAC was demonstrated at 1294.36 mm3 (LQ: 1099.68 mm3; HQ: 1627.84 mm3). CONCLUSIONS: In the present study, the morphometric properties of the temporal bone cavities were analysed. The results showed that the total volume of the MAC was, on average, lower in women than in men. This should be taken into account when performing procedures on the mastoid, such as mastoidectomies. It is hoped that the results of this study can help reduce potential surgical complications associated with otological procedures.

The petroclinoid ligament: a meta-analysis of its morphometry and prevalence of mineralization with a review of the literature.

BACKGROUND: The petroclinoid ligament (PCL) is an important structure in the petroclival region. The anatomy of the PCL and its relationship with the surrounding structure is highly variable. The aim of this study was to estimate the morphometry, prevalence of mineralization, and anatomy of the PCL. To achieve this, the authors carried out a meta-analysis, including all studies that report extractable data on the PCL. MATERIALS AND METHODS: Major online medical databases such as PubMed, Scopus, ScienceDirect, Web of Science, SciELO, BIOSIS, Current Content Connect, Korean Journal Database, and Russian Citation Index were searched to gather all studies regarding the anatomical characteristics, morphometry, and relationship with the anatomical surroundings of the PCL. RESULTS: A total of 25 studies were included in this meta-analysis. Data were gathered and analysed in eight categories: (1) mineralization of the PCL, (2) relationship of the abducens nerve with the PCL, (3) relationship of the dorsal meningeal artery with the PCL, (4) shape, number, and continuity of the PCL, (5) PCL anterior attachment, (6) PCL anterior attachment point on bone, (7) PCL posterior attachment point on bone, (8) morphometric features of the PCL. CONCLUSIONS: In conclusion, the authors of the present study believe that this is the most accurate and up-to-date meta-analysis regarding the morphology and mineralization of the PCL. The data provided by the present study may be a useful tool for surgeons performing neurosurgical procedures, such as endoscopic transnasal surgeries. Detailed anatomical knowledge of the petroclival region can surely prevent surgical complications when operating in this area.

Management of ponatinib dosing in chronic myeloid leukemia patients.

Ponatinib (Iclusig®, Takeda/Incyte) is a third-generation highly-potent-pan-inhibitor of tyrosine kinases, active in all single resistance ABL kinase mutations including the T315l mutation. It is approved to treat of chronic myeloid leukemia (CML) in every phase of disease-resistant or intolerant to second-generation tyrosine kinase inhibitors (2GTKIs) and for whom imatinib is not clinically appropriate as well as for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukemia (ALL). The approved starting dose for ponatinib is 45 mg once daily. Available data revealed ponatinib dose-dependent increased risk of cardiovascular toxicity. There is still no consensus about the optimal, initial dose of ponatinib and its management during therapy. It is crucial to start treatment with the risk-adjusted dose and assess the benefit-risk profile of ponatinib dosing. Evaluation of dosing modification should be considered during treatment, mainly if toxicity occurs. Our study summarizes current knowledge and recommendations about the choice of starting dose of ponatinib and management of ponatinib dosing during the treatment.

Thalidomide exerts distinct molecular antileukemic effects and combined thalidomide/fludarabine therapy is clinically effective in high-risk chronic lymphocytic leukemia.

Thalidomide represents a promising immunomodulatory drug that targets both leukemia cells and the tumor microenvironment. We treated patients with chronic lymphocytic leukemia (CLL) with a combined thalidomide/fludarabine regimen and monitored cellular and molecular changes induced by thalidomide in vivo before fludarabine treatment. Thalidomide was given daily (100 mg p.o. per day) and fludarabine was administered on days 7-11 (25 mg/m(2) i.v. per day) within each 4-week cycle (maximum of 6 cycles). Twenty patients received thalidomide/fludarabine as first-line therapy and 20 patients were previously treated. Unmutated IgVH mutation status was found in 36 cases and 13 had high-risk cytogenetic aberrations (del17p, del11q). The overall response rate was 80 and 25% for untreated and previously treated patients, respectively. Although thalidomide reduced the number of CLL cells, the number of CD3 lymphocytes showed no significant change, but the number of CD4(+)CD25(hi)FOXP3(+) regulatory T cells (Tregs) was significantly decreased. Gene expression profiling revealed a thalidomide-induced signature containing both targets known to have a function in immunomodulatory drug action as well as novel candidate genes. Combined thalidomide/fludarabine therapy demonstrated efficacy in high-risk patients with CLL. Furthermore, our study provides novel biological insights into thalidomide effect, which might act by enhancing apoptosis of CLL cells and reducing Tregs, thereby enabling T-cell-dependent antitumor effect.

Single brain metastasis from a minute, well differentiated, but invading beyond the tunica muscularis mucosa rectal carcinoid.

We report the case of a 48-year-old woman with small-sized (< 10 mm), highly differentiated, aggressive rectal carcinoid, who developed a solitary distant metastasis to the brain. The primary lesion, initially removed by conventional polypectomy, invaded the mucosa/tunica muscularis mucosa and had positive resection margins. Afterwards, an assessment of 5-hydroxyindoloacetic acid (5-HIAA) 24 h urine excretion revealed a significantly increased level. Thus, a partial rectal resection was performed. Because of constantly elevated carcinoid markers: serum chromogranin A (CGA) and 5-HIAA, a somatostatin receptor scintigraphy was performed, which disclosed a focus of pathological marker accumulation in the left frontal area. The pathological finding after neurosurgical excision was meningioma. An unexpected normalization of the biochemical markers prompted us to verify this diagnosis. The final histopathological report was a well-differentiated neuroendocrine brain metastasis. Our case shows that in well differentiated, of diameter < 10 mm rectal carcinoids, an invasion even beyond the mucosa/tunica muscularis mucosa seems to be an independent factor predicting a malignant metastatic potential of these tumors. Hence, in such cases, behind the endoscopic submucosal resection with ligation device a more radical surgery should be considered. Additionally, a systematic CGA and 5-HIAA follow-up assessment and whole body somatostatin receptor scintigraphy, if necessary, are required.

The clinical significance of ZAP-70 and CD38 expression in B-cell chronic lymphocytic leukaemia.

BACKGROUND: B-cell chronic lymphocytic leukaemia (B-CLL) is a disease with a highly variable clinical course; some patients never need treatment, while others require intensive treatment early after diagnosis. Recently, some new prognostic factors, such as IgVH mutational status, ZAP-70 and the expression of CD38 in leukaemic cells were introduced to identify attenuated versus progressive types of CLL bearing the potential to facilitate risk-adapted treatment strategies. PATIENTS AND METHODS: To evaluate the clinical value of ZAP-70 and CD38 as predictors of disease progression we assessed the expression of these markers by the flow cytometry method in 156 B-CLL patients. RESULTS AND CONCLUSIONS: Both ZAP-70 and CD38 expression were shown to predict the clinical course of the disease, while ZAP-70 expression appeared to be more predictive than CD38 expression and more relevant in defining the cases of B-CLL responsive or refractory to first line chemotherapy. A simultaneous evaluation of ZAP-70 and CD38 expression allowed distinguishing the patients groups with the most favourable prognosis as well as those with the worst. Taken together we recommend assessing both ZAP-70 and CD38 protein expression for the definition of prognostic subgroups in patients with B-CLL.

Intravascular B-cell lymphoma in a 38-year-old woman: a case report.

Intravascular lymphoma (IVL) is a rare aggressive disease characterised by the presence of lymphoma cells only in the lumina of small vessels, particularly capillaries. Only about 200 cases have been reported in the world (some of them retrospectively). IVL is predominantly of B-cell lineage origin but occasionally T-cell lineage occurs. Multiple organs may be involved and a variety of clinical presentations have been described. These include nephrotic syndrome, pyrexia and hypertension, breathlessness and haemolytic anaemia, leukopoenia, pancytopoenia and disseminated intravascular coagulation. We report a case of a 38-year-old woman with a highly aggressive clinical course of IVL. She was admitted to the Department of Neurosurgery because of spondylolisthesis of L5-S1 qualified to surgery. During hospitalisation haemolytic anaemia, thrombocytopoenia and splenomegaly were observed and she was admitted to the Department of Haematology for diagnosis. During her staying in the hospital, new symptoms, such as kidney and liver failure, occurred and the central nervous system was involved. The clinical course was very rapid and progressive. Corticosteroid therapy was started but the disease soon led to the fatal outcome. Diagnosis was established at post-mortem examination.

[Influence of abnormalities of TP53 and ATM genes for course of B-cell chronic lymphocytic leukemia]. / Geny TP53 i ATM i wplyw ich anomalii na przebieg przewleklej bialaczki limfatycznej B-komórkowej.

Uncontrolled cell proliferation is the hallmark of cancer, and tumour cells have typically acquired damage to genes that directly regulate their cell cycles. Genes that link checkpoint controls to cancer and other related genetic disease include the TP53 and ATM genes. The abnormalities of these genes are clearly associated with particular forms of the B-cell chronic lymphocytic leukemia and poor prognosis.

[Unusual cases of non-Hodgkin's lymphomas--case reports]. / Niezwykle przypadki chloniaków zlosliwych--opis przypadków.

We describe 4 cases of non-Hodkin's lymphomas that were interesting because of their curiosal clinical courses and spontaneous complete remissions during the course of high malignancy lymphoma. We present three of them for the first time in Poland. Case 1: a 61-year old woman was admitted to the hospital because of the headache, lasting for 4 months before hospitalization and right hemiparesis. CT scans revealed the presence of tumor in the temporo-occipital region. The diagnosis of B-cell lymphoma was established at histopathological examination of the postoperative material. Co60--therapy of these region was applied after the operation with good response. Case 2: a 38-year woman was admitted to the hospital because of L5-S1 spondylolisthesis to operate it. During the hospitalization haemolytic anaemia of unknown origin, thrombocytopoenia, splenomegaly, fever and rising acute insufficiency of kidneys, heart, liver and CNS were occurred. The patient died, despite applying corticosteroidotherapy. The diagnosis of intravascular lymphoma was established at postmortem examination. Case 3: a 51-year old woman was admitted to the hospital with diagnosis: anaplastic non-Hodgkin lymphoma B-cell type high malignancy established after the double histopathological examination of lymph nodes and biopsy of the lung. At the admission to the Department of Haematology we stated absolute regression of these changes. The patient had been only observed in the Outpatient Department over 1 year. She died after 6 months since the beginning of the relapse despite intensive chemotherapy. Case 4: a 43-year old man was admitted to the hospital because of great hyperleukocytosis, hepatosplenomegaly and neurological symptoms. The diagnosis: chronic prolymphocytic leukaemia was established. The cerebrospinal fluid examination showed presence of mononuclears which infiltrated CNS. CT scans of the brain revealed leucaemic infiltrations of the hemispheres and cerebellum. The patient died despite intensive therapy due to rising progressive multiorgan failure.

[CD43 in B-cell chronic lymphocytic leukemia]. / CD43 w przewleklej bialaczce limfatycznej B-komórkowej.

CD43 (other names: sialophorin, leukosialin, sialoglycoprotein of white blood cells) is an integral cell membrane mucin. In population of peripheral B cells CD43 occurs only on activated B cells and CD5 positive B cells. These last cells create neoplasm population in patients with B-cell chronic lymphocytic leukemia (B-CLL). Anti-CD43 monoclonal antibodies are used routinely in investigations of tissue fragments in cases of non-Hodgkin's lymphoma, whereas we did not find publication on theme of CD43 expression on peripheral blood B cells in patients with B-cell chronic lymphocytic leukemia. Wherefore advisable appeared estimation CD43 expression on B-CLL cells and comparison it with expression of typical B-CLL markers--such as CD5 and CD6. Immunological phenotype of peripheral blood and bone marrow lymphocytes has been evaluated using flow cytometry (Cytoron Absolute Ortho-Diagnostic Systems) and two-color staining. Twenty six untreated patients with B-CLL were studied. Because on well-known correlations between CD43 expression and metastasis potential of tumor, patients were divided on two groups differing score of total tumor mass (score TTM). Score TTM was evaluated according to criterion of Jaksic and Vitale. Twelve patients whose TTM score was equal or lower than 9 and median lymphocytosis was 24.6 x 10(9) in microliter were included in group I. 14 patients whose TTM score was higher than 9 were included in group II. Median lymphocytosis in these patients was 152.6 x 10(9) in microliter. The median percentage of CD43+/CD19+ cells in peripheral blood was 62.6% in the group I, and 75% in the group II (p < 0.05). Median fluorescence intensity (MFI) of CD43 antigen was 87.7 in the I group comparing to 77.4 in the group II. So one observed tendency to lowering MFI during tumor growing but the difference was not significant (p = 0.25). In peripheral blood during progression of disease more clearly than CD43+ cells increased percentage of CD5+ and CD6+ cells. The median percentage of CD19+/CD5+ cells was 62.7% in the group I, 82.4% in the group II and the difference was significant (p < 0.002). The difference in the median percentages CD6+/CD19+ cell 71.8% in group I and 84.3% in the II one were also significant (p < 0.03). MFI of CD5 and also CD6 antigens did not change in course of disease. Moreover, examination of CD43 and CD5 expression in marrow additionally to blood study were performed in 12 cases (6 from group I, 2 from group II and 4 new not included). The median percentage of CD43+/CD19+ cell was 35.1% in blood and 43.7% In marrow, in contrast to these results was the median percentage of CD19+/CD5+ cell, which was higher in peripheral blood (70.4%) than in bone marrow (60.9%). The results of this study indicate that CD43 is present on peripheral blood B-CLL cells. Moreover, percentage of these cell increases during progression of disease however more weakly than percentage of CD5 and CD6 positive cells. Expression of CD43 is independent from expression CD5 and CD6 and diminishes during tumor mass increasing, what can depended from releases exocellular domains of CD43. CD43+ cell from B-CLL patients have a tendency to accumulation in tissues what is illustrated by higher percentage of CD43+ cell in bone marrow than in peripheral blood.

[Expression of CD5 antigen in B and T cells from umbilical cord blood, from blood of healthy adults and patients with chronic lymphocytic B-cell leukemia (PBL-B)]. / Ekspresja czasteczki CD5 na komórkach B i T we krwi pepowinowej, we krwi doroslych osób zdrowych i chorych na przewlekla bialaczke limfatyczna B-komórkowa (PBL-B).

Antigen CD5 is the glycoprotein which belong to the scavenger receptor cysteine-rich family. Mainly there is on the T cells subpopulation. During fetal life B CD5+ cells are major subpopulation of B cells in the spleen, lymph nodes and there are also in the cord blood. In adult CD5+ cells are minor subpopulation (27%) of B cells from the peripheral blood. CD5 there are on chronic lymphocyte leukaemia B cells (B-CLL) also. Usually expression CD5 on B-CLL cells associated with weak or lack expression of the surface immunoglobulins and CD79 beta, CD20, CD22, CD21 (CR-2), CD35 (CR-1) antigens. It appeared interesting to compare the expression of CD5 antigen (the mean fluorescence intensity--MFI of CD5) on B cells from the cord blood, adults peripheral blood and B-CLL patients. MFI of CD5 on B and T cells were also compared in each groups. MFI of CD 19 was studied too. Lymphocytes from the cord blood (11 assays), adult peripheral blood of healthy volunteers (18 assays) and the peripheral blood of no treated patients with B-CLL (56 assays) were studied. The immunological phenotype of lymphocytes was evaluated with the monoclonal antibodies anti-CD5 and anti-CD19 by the flow cytometry method. We have demonstrated that MFI of CD5 on B cells from patients with B-CLL was strongest and weakest from normal individuals. MFI of CD5 on T cells from patients with B-CLL is stronger in comparison to healthy volunteers. MFI of CD19 is weakest on cells from patients with B-CLL and strongest in normal individuals. On the basis of the our results and other medical papers we suggest on the one hand that biology of B-CLL depend on deficit antigens specific for B cells lines on the other hand depend on overexpression of CD5 antigens on leukaemic B and T cells also.

[A case of chronic B cell lymphocytic leukemia with expression of CD8 antigen on leukemic cells]. / Przypadek przewleklej bialaczki limfatycznej B komórkowej z ekspresja antygenu CD8 na bialaczkowych komórkach.

CD8 antigen is present on the surface of cytotoxic-suppressor T cells, NK cells and majority of thymocytes. Expression of CD 8 is associated with CD 3 antigen, which is a part of a T cell receptor. However, CD 8 antigen is undetectable on normal B cells. In sporadic cases of B cell-chronic lymphocytic leukaemia (B-CLL) it was found on leukaemic B cells. We report a case of B-CLL of benign course with CD19+, CD5+, CD40+, CD19+, CD20+, CD19+, CD19+HLADR+ leukaemic cells expressing CD8 antigen on CD19+ leukaemic cells. It seems that original neoplasms source was localized out of bone marrow. We suggest that the origin of the target cell for neoplasms transformation could be CD5+ B cell and CD8+ T cell gamma + delta + CD8+.

[T lymphocyte subpopulations in B-cell chronic lymphocytic leukemia patients with a different percentage of CD4+ helper T cells in bone marrow]. / Subpopulacje limfocytów T u chorych z przewlekla bialaczka limfatyczna B-komórkowa rózniacych sie odsetkami pomocniczych komórek T CD4+ w szpiku.

Heterogeneity of B-cell chronic lymphocytic leukemia (B-CLL) may by partial an explanation of the ability of CLL cells to interact with the environment and it seems to be not related exclusively to cytogenetic abnormalities. For this reason T cell subpopulations were analysed in bone marrow and peripheral blood in two selected groups of B-CLL patients. These groups differed significantly in percentages of CD4+ helper T cells in bone marrow. In the first group (11 patients) percentage of CD4+ cells was higher than 9 p.c., in the second (10 patients) this percentage was equal, or lower than 2 p.c. Moreover these groups differed also in total tumor mass score (TTM-score) according to the criteria of Jaksic and Vitale. TTM-score in the first group was 9.7 in the second--22.9. In the first group CD4- cells predominated over CD8+ cytotoxic suppressor cells, as well as CD4+ CD45RO+ helper-inducer cells predominated over CD4+ CD45RA+ suppressor-inducer cells. In the second group we observed some superiority of CD8+ and CD4+ CD45RA+ cells. We can speculate that the predominance of CD4+ and CD4+ CD45RO+ cells over CD8+ and CD4+ CD45RA+ cells in bone marrow facilitate the proliferation or inhibits the apoptosis of CLL cells when the TTM-score is small. On the contrary when the TTM-score is larger, than the leukemic cells expanded in bone marrow without concomitant helper cells.

[Morbidity of multiple myeloma in material from the Hematology Clinic AM in Lublin after the accident in Chernobyl]. / Zachorowalnosc na szpiczaka plazmocytowego w materiale Kliniki Hematologii AM w Lublinie po wybuchu w Czarnobylu.

The average dosage of radiation which was measured in Poland during the year after damage of the nuclear power in Chernobyl (according to UNSCEAR) was 0.27 mSv, which gives 11% natural radiation dosage in the period of one year (2.6 mSv). Disturbances of cells genome caused by radiation are possible because of big dosage of radiation in Lublin region. It was interesting to define morbidity and mortality of multiple myeloma (MM) after the damage in Chernobyl. The average latent period of MM is about 20 years (like thyroid carcinoma). The increase of thyroid carcinoma morbidity after the damage of Chernobyl nuclear power plant in Byelorussia. Ukraine, Russia was observed. The increased morbidity rate of MM among patients of Haematologic Department (especially in the third stage of disease) and the increased mortality rate in Lublin region was confirmed.