Prognostic Outcome of Mesenchymal Transition Biomarkers in Correlation with EGFR Expression in Epithelial Ovarian Carcinoma Patients.

BACKGROUND: CD44 is an epithelial-mesenchymal transition (EMT) surface receptor that regulates the interactivity between the cells and the extracellular matrix, thereby promoting cell migration. The epidermal growth factor receptor (EGFR) family is a trans-membrane kinase-related protein. It regulates cell adhesion proteins, which may promote cell proliferation and invasiveness. Mesenchymal epithelial transition (MET) is another EMT receptor that stimulates cell proliferation, invasion, survival, and angiogenesis. This study aimed to evaluate the prognostic impact of CD44, EGFR expressions, and MET gene amplification in epithelial ovarian cancer (EOC). METHODS: This is a retrospective cohort study, including 85 cases of EOC. CD44 and EGFR expressions were evaluated in both epithelial and stromal cells by immunohistochemistry. Tumor cells also underwent a cytogenetic analysis using fluorescent in situ hybridization (FISH) to detect MET gene amplification. RESULTS: High CD44 expression in tumors was significantly associated with serous subtypes (P=0.001), peritoneal deposits (P=0.002), and advanced stage (P=0.002). EGFR high tumor expression demonstrated a significant association with lymph node metastasis (P=0.038) and the advanced stage of EOC (P=0.016). Increased copy number of the MET gene was significantly associated with partial therapy response (P=0.030).  CD44 and EGFR tumor high expression was associated with poor overall survival (OS). In addition, MET gene gain in tumors was associated with a shorter OS (P=0.000). CONCLUSION: EMT biomarkers (CD44 and MET) and EGFR expression in EOC are independent prognostic factors for OS. MET gene increase copy number was detected in cases of serous neoplasm and associated with poor survival and minimal therapy response.

Cytogenetic profile of adult acute myeloid leukemia in Egypt: a single-center experience.

BACKGROUND: Acute myeloid leukemia (AML) is a diverse disease characterized by the expansion of blasts of myeloid lineage. Cytogenetic testing is the cornerstone for risk stratification of AML patients. Geographical and environmental factors may play a very important role in the development of leukemia and several differences in genetic profile may be seen among different ethnicities. In our study, we evaluated cytogenetic findings of adult AML patients in South Egypt. METHODS: Cytogenetic testing (karyotyping and M-FISH) was performed for 120 adult patients with AML. Twenty metaphases were analyzed for each patient. RESULTS: In our study, the median age of AML patients was 36.5 years, with an age range between 18 and 86 years. 56.7% of patients had normal karyotypes and 43.3% of patients had clonal cytogenetic abnormalities. t (15;17) was the most detected structural abnormality, and + 8 was the most detected numerical abnormality. Regarding cytogenetic risk stratification, 65% of patients were in the intermediate-risk category. CONCLUSION: The cytogenetic profile of AML patients in our locality showed some differences and some similarities with cytogenetic profiles in different Arab, Asian and Western countries. Further studies are needed using advanced techniques such as next-generation sequencing and optical genome mapping to elucidate more ethnic and geographic genetic heterogeneity among different countries.

Fatigue in rheumatoid arthritis patients: association with sleep quality, mood status, and disease activity / Fatiga en pacientes con artritis reumatoide: asociación con la calidad del sueño, el estado de ánimo y la actividad de la enfermedad

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by polyarthritis and systemic manifestations. RA-fatigue is a significant problem and adds on disease burden. Sleep disturbance, depression, and disease activity are suggested contributing factors to RA-fatigue; however, their combined role did not examine before among Egyptian RA patients. The objective of the study was to investigate the presence of fatigue, sleep and mood disturbances in RA patients. Also, to evaluate the possible association of poor sleep, depression, and disease activity with RA-fatigue. METHODS: This cross-sectional study included 115 RA patients diagnosed according to the 2010 ACR-EULAR criteria and 46 age and sex matched controls. Fatigue using the Multidimensional Assessment of Fatigue-Global Fatigue Index, sleep using the Pittsburgh Sleep Quality Index and mood status using Beck Depression Inventory were assessed for all participants. RA disease activity was evaluated using disease activity score-28 joints. RESULTS: RA patients had higher mean fatigue, sleep disturbance, and depression scores (27.2±8.9, 6.4±3.6, and 12.8±7.3; respectively) than controls (22.7±7, 4.8±3, 7.8±5.9; respectively) (P<.05). Poor sleep, depression and higher disease activity were significantly correlated with fatigue (r=0.4, r=0.65, r=0.55; respectively) (P<.001). The three variables may explain up to 49.1% of the variation in fatigue on multiple regression analysis. CONCLUSION: Fatigue, poor sleep, and depression are more common in Egyptian patients with RA. A remarkably higher fatigue was associated with poor sleep, depression, and high disease activity, thus monitoring these silent comorbidities in clinical practice is required

OBJETIVOS: La artritis reumatoide (AR) es una enfermedad inflamatoria crónica, caracterizada por poliartritis y manifestaciones sistémicas. La fatiga asociada a AR es un problema importante y aumenta la carga de la enfermedad. La alteración del sueño, la depresión y la actividad de la enfermedad son factores sugeridos que contribuyen a la fatiga asociada a AR; sin embargo, su papel no se ha examinado previamente en pacientes egipcios con AR. El objetivo del estudio fue investigar la presencia de fatiga y alteraciones del sueño y humor en pacientes con AR. Además, evaluar la posible asociación del sueño deficiente, depresión y la actividad de la enfermedad con la fatiga asociada a AR. MÉTODOS: Este estudio transversal incluyó 115 pacientes con AR, diagnosticados según los criterios de la ACR-EULAR 2010 y 46 pacientes de control emparejados por edad y sexo. Se evaluó en todos los participantes la fatiga mediante el índice de evaluación multidimensional de la fatiga y la fatiga global, el sueño utilizando el índice de calidad del sueño de Pittsburgh y el estado de ánimo mediante el Inventario de Depresión de Beck. La actividad de la enfermedad de la AR se evaluó utilizando la medida de la actividad de enfermedad-28 articulaciones. RESULTADOS: Los pacientes con AR presentaron en promedio una mayor fatiga, alteración del sueño y puntuaciones de depresión (27,2±8,9; 6,4±3,6 y 12,8±7,3, respectivamente) que los pacientes de control (22,7±7; 4,8±3 y 7,8±5,9, respectivamente) (p < 0,05). El sueño deficiente, la depresión y una mayor actividad de la enfermedad se correlacionaron significativamente con la fatiga (r=0,4; r=0,65; r=0,55, respectivamente) (p < 0,001). Las 3 variables pueden explicar hasta el 49,1% de la variación en fatiga en el análisis de regresión múltiple. CONCLUSIÓN: La fatiga, el sueño deficiente y la depresión son más comunes en pacientes egipcios con AR. Una notablemente alta fatiga se asoció con un sueño deficiente, depresión y alta actividad de la enfermedad, por lo que se requiere el control de estas comorbilidades silenciosas en la práctica clínica

Impact of DAXX and ATRX expression on telomere length and prognosis of breast cancer patients.

BACKGROUND: Telomere stability is one of the hallmarks of cancer that promotes cellular longevity, the accumulation of genetic alterations, and tumorigenesis. The loss of death domain-associated protein (DAXX) and α-thalassemia/mental retardation X-linked protein (ATRX) plays a role in telomere lengthening and stability. This study aims to evaluate the prognostic significance of telomere length (TL) and its association with DAXX and ATRX proteins in breast cancer (BC). Our study used the FISH technique to detect peptide nucleic acid (PNA) in the peripheral blood cells of a cohort of BC patients (n = 220) and a control group of apparently healthy individuals (n = 100). Expression of DAXX and ATRX proteins was evaluated using immunohistochemistry (IHC) in all BC tissues. RESULTS: Patients with a shorter TL had worse disease-free survival (DFS) and overall survival (OS). There were significant associations between shorter TL and advanced disease stages, lymph node metastasis, and positive HER2/neu expression. DAXX protein expression was significantly correlated with TL. Lower DAXX expression was significantly with shorter DFS. CONCLUSION: Assessing TL can be used as a worthy prognostic indicator in BC patients. Specifically, short TL had a poor impact on the prognosis of BC patients. Low DAXX expression is associated with poor outcomes in BC. Further mechanistic studies are warranted to reveal the underlying mechanisms of these associations.

Fatigue in Rheumatoid Arthritis Patients: Association With Sleep Quality, Mood Status, and Disease Activity.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterized by polyarthritis and systemic manifestations. RA-fatigue is a significant problem and adds on disease burden. Sleep disturbance, depression, and disease activity are suggested contributing factors to RA-fatigue; however, their combined role did not examine before among Egyptian RA patients. The objective of the study was to investigate the presence of fatigue, sleep and mood disturbances in RA patients. Also, to evaluate the possible association of poor sleep, depression, and disease activity with RA-fatigue. METHODS: This cross-sectional study included 115 RA patients diagnosed according to the 2010 ACR-EULAR criteria and 46 age and sex matched controls. Fatigue using the Multidimensional Assessment of Fatigue-Global Fatigue Index, sleep using the Pittsburgh Sleep Quality Index and mood status using Beck Depression Inventory were assessed for all participants. RA disease activity was evaluated using disease activity score-28 joints. RESULTS: RA patients had higher mean fatigue, sleep disturbance, and depression scores (27.2±8.9, 6.4±3.6, and 12.8±7.3; respectively) than controls (22.7±7, 4.8±3, 7.8±5.9; respectively) (P<.05). Poor sleep, depression and higher disease activity were significantly correlated with fatigue (r=0.4, r=0.65, r=0.55; respectively) (P<.001). The three variables may explain up to 49.1% of the variation in fatigue on multiple regression analysis. CONCLUSION: Fatigue, poor sleep, and depression are more common in Egyptian patients with RA. A remarkably higher fatigue was associated with poor sleep, depression, and high disease activity, thus monitoring these silent comorbidities in clinical practice is required.

Assessment of human epidermal growth factor receptor 2/neu gene amplification and expression as a biomarker for radiotherapy and hormonal-treated breast cancer patients in upper Egypt.

BACKGROUND: Breast cancer plays major public health in Egyptian women. In upper Egypt, There is an increase in the incidence of breast cancer compared to other Egyptian areas without know the reasons. In this study, we aimed to evaluate the potential of HER-2/neu status as one of the important markers to classify the women suffering from breast cancer in upper Egypt and monitoring the responsiveness to different therapies. SETTINGS AND DESIGN: The present study was performed on 67 female breast cancer patients in the South Egypt Cancer Institute to evaluate HER-2/neu gene amplification and expression. PATIENTS AND METHODS: Tissue samples were used for immunohistological analysis of endocrine receptors, HER-2/neu, and HER-2/neu gene amplification. In addition, the blood samples were also used to determine HER-2/neu gene expression. STATISTICAL ANALYSIS: All statistical analyses were performed using Chi-square test. The statistical difference is considered statistically significant at P < 0.05. RESULTS: There was a statistically significant association between HER-2/neu gene expression and the age of patients. There is decrease in the level of HER-2/neu mRNA expression in group treated with chemotherapy and group treated with chemotherapy and radiotherapy compared to each group baseline level of HER-2/neu mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy, and hormonal therapy revealed increase on the level of HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment. CONCLUSION: We need further studies on the large group of upper Egypt breast cancer patients to confirm that the level of HER-2/neu mRNA expression can be used as a marker for classified them and their response to different treatment.

The correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele.

This study aimed to assess the possible correlation between mammalian target of rapamycin (mTOR) gene expression and sperm DNA damage among infertile patients with and without varicocele. The study included sixty infertile males and fifty fertile males as controls. The infertile group was subdivided into the following subgroups: thirty males with varicocele and thirty males without varicocele. All subjects underwent medical history collection, clinical examination, semen analysis, sperm DNA integrity assessment, mTOR gene expression assessment and scrotal colour Doppler ultrasound. The mean mTOR gene expression in infertile patients with varicocele (23.52 ± 14.65) was significantly higher than that in infertile patients without varicocele (12.24 ± 12.44) and fertile control subjects (3.92 ± 3.26; p = 0.003 and p < 0.001 respectively). In the infertile varicocele-positive group, mTOR gene expression showed a significant negative correlation with sperm count (p = 0.028, r = -0.400) and progressive sperm motility (p = 0.038, r = -0.381), as well as a significant positive correlation with the sperm DNA fragmentation index (DFI; p = 0.001, r = 0.578). In the infertile varicocele-negative group, mTOR gene expression showed a significant negative correlation with progressive sperm motility (p = 0.018, r = -0.429) and a significant positive correlation with sperm DFI (p < 0.001, r = 0.673). In conclusion, according to these results, there is a significant positive correlation between mTOR gene expression and sperm DFI among infertile patients with and without varicocele.

Effect of Dexmedetomidine Added to Modified Pectoral Block on Postoperative Pain and Stress Response in Patient Undergoing Modified Radical Mastectomy.

BACKGROUND: The most common surgical procedure for breast cancer is the modified radical mastectomy (MRM), but it is associated with significant postoperative pain. Regional anesthesia can reduce the stress response associated with surgical trauma. OBJECTIVES: Our aim is to explore the efficacy of 1 µg/kg dexmedetomedine added to an ultrasound (US)-modified pectoral (Pecs) block on postoperative pain and stress response in patients undergoing MRM. STUDY DESIGN: A randomized, double-blind, prospective study. SETTING: An academic medical center. METHODS: Sixty patients with American Society of Anesthesiologists (ASA) physical status I-II (18-60 years old and weighing 50-90 kg) scheduled for MRM were enrolled and randomly assigned into 2 groups (30 in each) to receive a preoperative US Pecs block with 30 mL of 0.25% bupivacaine only (group 1, bupivacaine group [GB]) or 30 mL of 0.25% bupivacaine plus 1 µg/kg dexmedetomidine (group II, dexmedetomidine group [GD]). The patients were followed-up 48 hours postoperatively for vital signs (heart rate [HR], noninvasive blood pressure [NIBP], respiratory rate [RR], and oxygen saturation [Sao2]), visual analog scale (VAS) scores, time to first request of rescue analgesia, total morphine consumption, and side effects. Serum levels of cortisol and prolactin were assessed at baseline and at 1 and 24 hours postoperatively. RESULTS: A significant reduction in the intraoperative HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) starting at 30 minutes until 120 minutes in the GD group compared to the GB group (P < 0.05) was observed. The VAS scores showed a statistically significant reduction in the GD group compared to the GB group, which started immediately up until 12 hours postoperatively (P < 0.05). There was a delayed time to first request of analgesia in the GD group (25.4 ± 16.4 hrs) compared to the GB group (17 ± 12 hrs) (P = 0.029), and there was a significant decrease of the total amount of morphine consumption in the GD group (9 + 3.6 mg) compared to the GB group (12 + 3.6 mg) (P = 0.001). There was a significant reduction in the mean serum cortisol and prolactin levels at 1 and 24 hours postoperative in the GD patients compared to the GB patients (P < 0.05). LIMITATIONS: This study was limited by its sample size. CONCLUSION: The addition of 1 µg/kg dexmedetomidine to an US-modified Pecs block has superior analgesia and more attenuation to stress hormone levels without serious side effects, compared to a regular Pecs block in patients who underwent MRM. KEY WORDS: Postoperative pain, dexmedetomidine, Pecs block, stress response, breast surgery.

The molecular basis of cytotoxicity of α-spinasterol from Ganoderma resinaceum: Induction of apoptosis and overexpression of p53 in breast and ovarian cancer cell lines.

Despite advances in therapy of breast and ovarian cancers, they still remain among the most imperative causes of cancer death in women. The first can be considered one of the most widespread diseases among females, while the latter is more lethal and needs prompt treatment. Thus, the research field can still benefit from discovery of new compounds that can be of potential use in management of these grave illnesses. We hereby aimed to assess the antitumor activity of the phytosterol α-spinasterol isolated from Ganoderma resinaceum mushroom on human breast cancer cell lines (MCF-7, MDA-MB-231), as well as, on human ovarian cancer cell line (SKOV-3). The anti-tumor activity of α-spinasterol, isolated from the mycelial extract of the Egyptian G. resinaceum, on human breast and ovarian cancer cell lines was evaluated by MTT cell viability assay and AnnexinV/propidium iodide apoptosis assay. The molecular mechanism underlying this effect was assessed by the relative expression of the following markers; tumor suppressor (p53, BRCA1, BRCA2), apoptotic marker (Bax) and cell cycle progression markers (cyclin dependent kinases cdk4/6) using real-time PCR. Cell cycle analysis was performed for the three investigated cancer cell lines to explore the effect on cell cycle progression. Our findings showed that α-spinasterol exhibited a higher antitumor activity on MCF-7 cells relative to SKOV-3 cells, while its lowest antitumor activity was against MDA-MB-231 cells. A significant increase in the expression of p53 and Bax was observed in cells treated with α-spinasterol, while cdk4/6 were significantly down-regulated upon exposure to α-spinasterol. Cell cycle analysis of α-spinasterol treated cells showed a G0 -G1 arrest. In conclusion, α-spinasterol isolated from G. resinaceum mushroom exerts a potent inhibitory activity on breast and ovarian cancer cell lines in a time- and dose-dependent manner. This can be reasonified in lights of the compound's ability to increase p53 and Bax expressions, and to lower the expression of cdk4/6.

Acridine Orange and Flow Cytometry: Which Is Better to Measure the Effect of Varicocele on Sperm DNA Integrity?

We evaluated the effect of varicocelectomy on semen parameters and levels of sperm DNA damage in infertile men. A total of 75 infertile men with varicocele and 40 fertile men (controls) were included in this study. Semen analysis and sperm DNA damage expressed as the DNA fragmentation index using acridine orange staining and chromatin condensation test by flow cytometry were assessed before and 6 months after varicocelectomy. The patients were also followed up for 1 year for pregnancy outcome. Semen parameters were significantly lower in varicocele patients compared to controls (P < 0.05). Mean percentages of sperm DNA fragmentation and sperm DNA chromatin condensation in patients were significantly higher than those in controls (P < 0.05). After varicocelectomy, sperm DNA fragmentation improved significantly, whereas sperm chromatin condensation was not significantly changed. In 15 out of 75 varicocele patients, clinical pregnancy was diagnosed; those with positive pregnancy outcome had significant improvement in sperm count, progressive sperm motility, and sperm DNA fragmentation, but there was no significant difference in sperm DNA condensation compared to negative pregnancy outcome patients. We concluded from this study that acridine orange stain is more reliable method than flow cytometry in the evaluation of sperm DNA integrity after varicocelectomy.

Validation of an IGF-CTP scoring system for assessing hepatic reserve in Egyptian patients with hepatocellular carcinoma.

BACKGROUND: The Child-Turcotte-Pugh score (CTP) is the standard tool for hepatic reserve assessment in hepatocellular carcinoma (HCC). Recently, we reported that integrating plasma insulin-like growth factor-1 (IGF-1) level into the CTP score was associated with better patient risk stratification in two U.S. independent cohorts. Our current study aimed to validate the IGF-CTP score in patients who have different demographics and risk factors. PATIENTS AND METHODS: We prospectively recruited 100 Egyptian patients and calculated their IGF-CTP score compared to CTP score. C-index was used to compare the prognostic significance of the two scoring systems. Finally, we compared our results with our U.S. cohorts published data. RESULTS: IGF-CTP score showed significant better patient stratification compared to CTP score in the international validation cohort. Among CTP class A patients, who usually considered for active treatment and clinical trial enrollment, 32.5% were reclassified as IGF-CTP class B with significantly shorter OS than patients reclassified as class A with hazard ratio [HR] = 6.15, 95% confidence interval [CI] = 2.18 -17.37. CONCLUSIONS: IGF-CTP score showed significantly better patient stratification and survival prediction not only in the U.S. population but also in international validation population, who had different demographics and HCC risk factors.

Changes in platelet, coagulation, and fibrinolytic activities in mitral stenosis after percutaneous mitral valvotomy: role of hemodynamic changes and systemic inflammation.

Markers of platelet activity (P-selectin), fibrinolysis (d-dimer), thrombin activity (prothrombin fragments 1, 2 [PF1,2] and thrombin-antithrombin III complex [TAT]), and inflammation (interleukin 1ß [IL-1ß]) were measured in 65 patients with mitral stenosis (MS) before and 2 weeks after percutaneous mitral valvotomy (PMV) and in 23 controls. All markers were significantly higher than the control and significantly decreased after PMV. P-selectin change correlated with the changes in left atrial diameter (LAD), pulmonary artery systolic pressure (PASP), and IL-1ß. d-Dimer change had similar correlations, LAD, PASP, and IL-1ß. The PF1,2 change correlated with the change in IL-1ß. The TAT change correlated with the changes in LAD. The IL-1ß change correlated with the changes in PASP. In conclusion, MS is associated with heightened inflammatory, platelet, thrombin, and fibrinolytic activities that decrease after PMV. Altered hemodynamics and reduced inflammatory activity might have a possible role in these changes.

Cyclin D1 amplification in multiple myeloma is associated with multidrug resistance expression.

BACKGROUND: Cyclin D1 is involved in normal regulation of the cell cycle and in neoplasia. Inhibition of cyclin D1 function markedly attenuates the proliferation of fibroblasts of colon, esophageal, lung, and pancreatic cancer. However, the prognostic value of overexpression of cyclin D1 in multiple myeloma is still a point of debate. This study aimed at evaluating the effect of cyclin D1 gene amplification in multiple myeloma on overall survival and response to therapy. PATIENTS AND METHODS: Fifty patients with multiple myeloma were retrospectively studied. Cyclin D1 gene amplification was studied in bone marrow biopsies of these patients using FISH. An immunohistochemical study of the bone marrow biopsies was done to detect MDR1 protein expression. The correlations between the cyclin D1 gene amplification and overall survival and MDR1 expression were studied and analyzed statistically. RESULTS: Cyclin D1 gene amplification was found in 20% of myeloma patients and was associated with higher percentage of plasma cell infiltration of the bone marrow and increased liability for multiple osteolytic lesions. Cyclin D1-positive patients had a significantly lower progression-free and overall survival and higher levels of MDR1 compared with cyclin D1-negative patients. Cyclin D1 levels showed a highly statistically significant positive correlation with MDR1 levels (R, 0.8 and P < .0001). CONCLUSION: We suggest that there is an association between cyclin D1 gene amplification and disease severity, unfavorable prognosis, and increased expression of MDR1 in multiple myeloma patients.

Rearrangement of the myeloid/lymphoid leukemia gene in therapy-related myelodysplastic syndrome in patients previously treated with agents targeting DNA topoisomerase II.

BACKGROUND: Therapy-related acute myeloid leukemias (t-AML), with balanced translocations affecting the 11q23 point in the myeloid/lymphoid leukemia (MLL) gene, are one of the most serious complications of treatments with topoisomerase II inhibitors. However, only a few reports of t-AML exist. We aimed to study if these translocations are cumulative-dose-dependent, their frequency in therapy-related myelodysplastic syndrome and the relationship between their presence, the type of therapy and the response criteria. METHODS: This retrospective study included 120 patients with various malignancies (108 non-Hodgkin's lymphoma, 8 Hodgkin's disease and 4 neuroblastoma) in remission, being treated with topoisomerase 2 inhibitors; 74 had been diagnosed with therapy-related myelodysplasia and 46 did not have dysplasia. All bone marrow biopsy samples were evaluated by fluorescence in situ hybridization for 11q23 point breakage in the MLL gene. RESULTS: MLL gene rearrangement frequency was 6% in dysplastic versus 2% in nondysplastic groups; p < 0.001. It was associated with a worse overall survival (mean 13 ± 2 vs. 39 ± 3 months, log-rank p value <0.0001). It was dose-dependent with a cut-off value of 290 mg/kg of topoisomerase II inhibitors as assessed by ROC curve (area under the curve 0.84 ± 0.05, p < 0.0001). CONCLUSIONS: It is proposed that the MLL gene is etiopathogenetically relevant for hematological neoplasias transformation and survival.

Can Bcl-XL expression predict the radio sensitivity of bilharzial-related squamous bladder carcinoma? A prospective comparative study.

BACKGROUND: Local pelvic recurrence after radical cystectomy for muscle invasive bilharzial related squamous cell carcinoma accounts for 75% of treatment failures even in organ confined tumors. Despite the proven value of lymphadenectomy, up to 60% of patients undergoing cystectomy do not have it. These factors are in favor of adjuvant radiotherapy reevaluation. objectives: to evaluate the effect of adjuvant radiotherapy on disease free survival in muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder and to test the predictability of radio-sensitivity using the anti apoptotic protein Bcl-XL. METHODS: The study prospectively included 71 patients, (47 males, 24 females) with muscle invasive bilharzial related squamous cell carcinoma of the bladder (Stage pT2a-T3N0-N3M0) who underwent radical cystectomy in Assiut university hospitals between January 2005 and December 2006. Thirty eight patients received adjuvant radiotherapy to the pelvis in the dose of 50Gy/25 fractions/5 weeks (Group 1), while 33 patients did not receive adjuvant radiotherapy (group 2). Immunohistochemical characterization for bcl-xL expression was done. Follow up was done every 3 months for 12 to 36 months with a mean of 16 ± 10 months. All data were analyzed using SPSS version 16. Three years cumulative disease free survival was calculated and adjusted to Bcl-XL expression and side effects of the treatment were recorded. RESULTS: The disease free cumulative survival was 48% for group 1 and 29% for group 2 (log rank p value 0.03). The multivariate predictors of tumor recurrence were the positive Bcl-XL expression (odd ratio 41.1, 95% CI 8.4-102.3, p < 0.0001) and radiotherapy (odd ratio 0.19, 95% CI 0.05-0.78, p < 0.02). With Cox regression, the only independent multivariate predictor of radio-sensitivity was the Bcl-XL expression with odd ratio 4.6 and a p value < 0.0001. All patients tolerated the treatment with no life threatening or late complications during the period of follow up. CONCLUSIONS: Adjuvant radiotherapy for muscle invasive bilharzial related squamous cell carcinoma of the urinary bladder has potential effectiveness and minor side effects. Moreover, Bcl-XL expression is a valuable tool for predicting those who might not respond to this adjuvant treatment.

Tissue factor pathway inhibitor and P-selectin as markers of sepsis-induced non-overt disseminated intravascular coagulopathy.

Inflammation and coagulation occur concomitantly in sepsis. Thrombin activates platelet that leads to P-selectin translocation, which upregulate tissue factor (TF) generation. Tissue factor pathway inhibitor (TFPI) is an anticoagulant that modulates coagulation induced by TF. The term non-overt disseminated intravascular coagulation (DIC) refers to a state of affairs prevalent before the occurrence of overt DIC. It was suggested that an initiation of treatment in non-overt DIC has better outcome than overt DIC. This study investigated the role of TFPI level, P-selectin, and thrombin activation markers in non-overt and overt DIC induced by sepsis and its relationship to outcome and organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score. It included 176 patients with sepsis. They were admitted to the pediatric intensive care unit (ICU).They included 144 cases of non-overt DIC and 32 cases of overt DIC. There was a significant difference in hemostatic markers, platelet count, partial thromboplastin time (PTT), P-selectin, thrombin activation markers, TFPI, and DIC score between overt and non-overt DIC in both groups. It was noticed that P-selectin was positively correlated with DIC score, fibrinogen consumption, fibrinolysis (D-dimer), thrombin activation markers, and TFPI. Tissue factor pathway inhibitor was significantly correlated with fibrinolysis, DIC score, and prothrombin fragment 1+2. Sequential Organ Failure Assessment score was correlated with DIC score and other hemostatic markers in patients with overt DIC. To improve the outcome of patients with DIC, there is a need to establish more diagnostic criteria for non-overt-DIC. Plasma levels of TFPI and P-selectin may be helpful in this respect.

Diagnostic performance and predictive value of rheumatoid factor, anti-cyclic-citrullinated peptide antibodies and HLA-DRB1 locus genes in rheumatoid arthritis.

BACKGROUND: We evaluated the significance of the genes, defined as DRB1*04 or DRB1*01, in rheumatoid arthritis (RA) patients. We focused on the role of genetic and serologic markers to predict disease activity and destructive process of joints. METHODS: Sixty patients with RA were examined. Radiographic changes were evaluated by (Larsen score) and disease activity was measured by disease activity score 28 (DAS28). The markers analyzed were: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptides (anti-CCP2) and HLA-DRB1 alleles typed by PCR. RESULTS: In this study, anti-CCP antibodies, CRP, RF and AKA were detected in 83.3%, 56.7%, 71.7% and 52% of patients respectively. HLA-DRB1*01 was found in 45% of patients and 35% of them had one or two HLA-DRB1*04 alleles. According to DRB1*04 subtypes, (DRB1* 0405) was present in of 80% them. For prediction of grade of activity, the independent predictors were anti-CCP (OR 19.6), and DRB1*04 positive allele (OR 5.1). The combination of DRB1*04 + anti-CCP antibodies gave increase in the specificity and positive predictive value to 92% and 90 respectively. As regards to the prediction of radiological joint damage, the independent predictors were HLA-DRB1*04, HLA-DRB1*01, RF, and CRP > 18 (OR 5.5, 4.5, 2.5, 2.0 respectively). CONCLUSION: Our findings suggest that anti-CCP2 is superior to RF for the detection of RA and provided predictive information on joint destruction and disease activity. The presence of RA associated antibodies (ACCP or RF) and/or the SE genes are indicative for a poorer radiological outcome and higher grade of activity.

Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study.

OBJECTIVES: We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of TEL-AML1 fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD). METHODS: All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of TEL-AML1 fusion represented by disease course and survival. RESULTS: TEL-AML1 fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between TEL-AML1 fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of TEL-AML1 fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 +/- 1 month, in contrast to 28 +/- 5 month in its absence (P = 0.006). Also, the persistence at TEL-AML1 fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 +/- 2 months in the presence of MRD and it was 40 +/- 1 months in its absence. So, persistence of TEL-AML1 fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS. CONCLUSION: For most patients, the presence of TEL-AML1 fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of TEL-AML1 fusion as MRD has no additive prognostic value.

Bcl-XL and Bcl-2 expression in bilharzial squamous cell carcinoma of the urinary bladder: which protein is prognostic?

OBJECTIVES: Bcl-2 and Bcl-XL are the most important antiapoptotic members of the Bcl-2 family frequently overexpressed in bladder cancer. Overexpression of Bcl-XL bilharzial-related bladder cancer was associated with tumor progression. However, the negative prognostic value of Bcl-2 expression is still questionable. This work studied the expression of Bcl-XL and Bcl-2 immunohistochemically in bilharzial-related squamous cell carcinoma of the urinary bladder and determined their prognostic value in relation to recurrence after radical cystectomy. METHODS: A total of 72 patients with muscle-invasive bilharzial squamous cell carcinoma of the urinary bladder underwent radical cystectomy at our institution. The specimens were examined immunohistochemically for Bcl-XL and Bcl-2 expression. The patients were followed up for 3 years or until recurrence. The expression of Bcl-XL and Bcl-2 were related to the other prognostic indicators and patient survival. RESULTS: The expressions of both Bcl-2 and Bcl-XL were significantly different according to the grade of malignancy. Bcl-XL expression was significantly related to tumor recurrence, but Bcl-2 expression was not. CONCLUSIONS: To our knowledge, the present study is the first report of a negative prognostic value for Bcl-XL in bilharzial squamous cell carcinoma of the urinary bladder. However, this is another negative report on the prognostic value of bcl-2 in bilharzial bladder tumors.