Noha Y. Ibrahim

Survival of Mesothelioma in a Palliative Medical Care Unit in Egypt

BACKGROUND This study was to evaluate the survival of patients with pleural and intraperitoneal malignant mesothelioma and to investigate the efficacy of chemotherapy (CT) as well as radiotherapy (RTH) and surgery compared to best supportive care (BSC). MATERIALS AND METHODS Forty patients with malignant mesothelioma (38 with pleural and 2 with intraperitoneal) were enrolled. Twenty seven patients underwent (CT) chemotherapy of which 2 also received (RTH) and surgery was only for biopsy in 15/40. Combination chemotherapy included cisplatin-gemcitabine, cisplatin-navelbine and cisplatin (or carboplatin) with premetrexed. Thirteen patients received only best supportive care. RESULTS A total of 12 (30%) patients were male, and 28 (70%) female. Median age was 54.0 years and the male/female ratio was 1/2.33 (P=0.210). Residential exposure played a major role in two regions, Helwan and Shoubra, in 20% and 15%, respectively. Overall mean survival time was 13.9±2.29 months. That for patients who had received best supportive care was 7.57±1.85 months, for chemotherapy was 16.5±3.20 months, and multimodality treatment regimen 27±21.0 months (P=0.028). Kaplan-Meier survival did not significantly vary for sex, residence and the pathological types epithelial, mixed and sarcomatous. The median survival for performance status and treatment modalities was significant (P=0.001 and 0.028). Best supportive care using opioids with a mean dose of 147.1 mg (range 0-1680) of morphine sulphate produced good subjective response and reasonable quality of life but did not affect survival. CONCLUSIONS We conclude that CT prolongs survival compared to BSC in patients with malignant mesothelioma. Moreover, using escalating doses of opioids provides good pain relief and subjective responses.

Methylenetetrahydrofolate reductase gene polymorphisms (677C > T and 1298A > C) in Egyptian patients with non-hodgkin lymphoma

BACKGROUND Folate metabolism plays an essential role in Deoxyribonucleic acid (DNA) synthesis and methylation processes. Deviations in the flux of the folate may affect the susceptibility to various cancers including lymphoma. AIM The aim of this study was to investigate the genetic polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C/T and 1298A/C) and to evaluate its associations with the risk of Non Hodgkin lymphoma. MATERIALS AND METHODS The study included 50 patients with diffuse large B cell lymphoma (DLBCL) as well as 50 age matched apparently healthy volunteers (as control). All the subjects included in the study were genotyped for the detection of the MTHFR gene polymorphisms (677C > T and 1298A > C) by using restriction fragment length polymorphism (PCR-RFLP). RESULTS There were highly statistically significant differences between the 2 groups with respect to results of PCR-RFLP for MTHFR 677C→T polymorphism for CC genotype (P value = 0.001), statistically significant differences for CT (P value = 0.048) and TT (P value = 0.038) genotypes; however, no statistically significant differences regarding CC/CT or TT/CT alleles (P value = 0.052). Also, there were highly statistically significant differences between the patient and control groups with regards to the results of MTHFR1298 A/C polymorphism for the AA, AC genotypes as well as the AA/AC and CC/AC alleles (P value < 0.0001), and statistically significant difference regarding CC genotype (P value 0.0192). CONCLUSION In conclusion, this study demonstrated a significant association between the MTHFR polymorphisms and the risk of DLBCL. Thus the study could support that folate intake together with the genetic basis may help in modifying the risk to lymphoma.

Impact of bilateral breast cancer on prognosis: synchronous versus metachronous tumors.

BACKGROUND The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. MATERIALS AND METHODS Between 2005 and 2009 we identified 110 cases of bilateral breast cancer (BBC) ; 49 patients had synchronous (duration between the occurrence of carcinoma in both breasts was less than 12 months) and 61 had metachronous (duration was more than one year with no ipsilateral local recurrence). We compared the patient characteristics including age, menopausal status, clinical stage, tumor size, histological classification, lymph node status, and hormone receptor and Her-2 status. We also compared the treatment given and overall and disease free survival (DFS) of both groups. RESULTS Synchronous cases tend to present more aggressively than metachronous cases and age at first presentation adversely affects survival. The 5 year overall survival was 78.7% for metachronous and 60% for synchronous. Patients with positive hormonal status had better five year disease free survival in metachronous compared to synchronous cases, at 76% and 63%, respectively. Age at first presentation >45years had better DFS (65%) compared to those with age ≤45 years (52%) at 5 years follow up. CONCLUSIONS Patients with synchronous breast cancer may have worse prognosis. Young age and hormone receptor negative were risk factors in our study. Close follow up and early detection of contralateral breast cancer is mandatory.

The use of opioids at the end-of-life and the survival of Egyptian palliative care patients with advanced cancer.

BACKGROUND AND AIM One of the barriers to cancer pain control and palliative care (PC) development is the misconception that the use of opioids may hasten death. This concern is exaggerated when higher doses of opioids are used at the end-of-life. The aim of this study was to investigate the relationship between survival and the dose of opioids used at the end-of-life of patients with advanced cancer in an Egyptian PC setting. METHODS Retrospective review of the medical records of 123 patients with advanced cancer managed in an Egyptian cancer center-based palliative medicine unit (PMU). Patients were classified according to the last prescribed regular opioid dose expressed in milligrams of oral morphine equivalent (OME) per day (mg OME/24 h) into three groups: no opioid or low-dose group (<120 mg OME/24 h), intermediate-dose group (120-<300 mg OME/24 h) and high-dose group (≥300 mg OME/24 h). Survival was calculated from the date of first referral to the PMU to death. RESULTS The median age of patients was 53 years, breast cancer was the most common diagnosis (18%) and the majority (68%) died at home. Opioids were prescribed for pain control in 94% of patients and were prescribed on regular basis in 89%. The mean last prescribed opioid dose for the whole group of patients was 167 (±170) mg OME/24 h and it was highest among patients with pleural mesothelioma [245 (±258) mg OME/24 h]. The last prescription included no opioids or low-dose opioids in 57 (46%) patients, intermediate-dose in 42 (34%) and high-dose in 24 (20%). The estimated median survival was 45 days for the no opioid/low-dose group, 75 days for the intermediate-dose group and 153 days for the high-dose group (P=0.031). CONCLUSIONS The results suggest that the dose of opioids has no detrimental impact on the survival of patients with advanced cancer in an Egyptian PC setting. Further research is needed to overcome barriers to cancer pain control especially in settings with inadequate cancer pain control.

Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1) gene polymorphisms in Egyptian patients with acute myeloid leukemia

BACKGROUND The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the bodys ability to detoxify a range of potential leukemogens encountered in the environment. AIM OF WORK To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment. PATIENTS AND METHODS A total of 50 patients with acute myeloid leukemia (AML), as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and conventional polymerase chain reaction (PCR), respectively. RESULTS For GSTP1 313 A → G (GSTP1 Ile105Val) polymorphism, It was found that the wild genotype (AA) was significantly higher among control subjects (P value = 0.0277), while the frequency of heteromutant genotype (AG) and mutant G allele (AG + GG) was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively). For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005). CONCLUSION We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.

Cancer diagnosis disclosure preferences of family caregivers of cancer patients in Egypt

Family caregivers (FCs) of cancer patients are frequently seen as a barrier to honest communication with patients in Egypt. This study was conducted to investigate the attitude of FCs of cancer patients toward cancer diagnosis disclosure (CDD) and its determinants.

BAALC and ERG expression in Egyptian patients with acute myeloid leukemia, relation to survival and response to treatment.

AIM: Aim was to detect Brain and Acute Leukemia, Cytoplasmic (BAALC) and ETS-related gene (ERG) expression in patients with acute myeloid leukemia (AML) as well as to study their biologic and prognostic impact on the disease outcome and survival. PATIENTS AND METHODS: The current study was carried out on 44 patients with denovo acute myeloid leukemia, as well as 44 age and sex matched controls. The quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was performed for estimation of BAALC and ERG expression. RESULTS: The current study was carried out on 44 patients with denovo acute myeloid leukemia, as well as 44 age and sex matched controls. The quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was performed for estimation of BAALC and ERG expression. BAALC was expressed in 36 (81.82%) of AML cases versus 10 (22.72%) of the control group which was highly statistically significant (P < 0.001). While ERG was positive in 39(88.64%) of cases and 8(18.18 %) of controls and that was also highly statistically significant (P < 0.001). CONCLUSION: Further researches still needed to clarify the role of BAALC and ERG in the pathogenesis of leukemia and their importance as targets for treatment of AML.

Detection of orphan receptor tyrosine kinase (ROR-1) expression in Egyptian pediatric acute lymphoblastic leukemia.

Receptor tyrosine kinases, a group of tumor-associated antigens, were introduced as targets for cancer intervention strategies. The human orphan receptor tyrosine kinase-1 (ROR-1) is a member of this family. Overexpression of ROR1 has been reported in B-cell chronic lymphocytic leukemia. The aim of this study was to detect the expression profile of ROR1 in 54 pediatric acute lymphoblastic leukemia (ALL) patients. ROR1 was overexpressed in ALL as the ROR1/ β-actin ratio was higher in ALL children than in control group (P = 0.024). ROR1 is a potential tool for targeted immunotherapy in pediatric ALL patients.

Health-related quality of life: Impact of surgery and treatment modality in breast cancer

Background: Breast cancer is the most common malignancy among women leading to serious sequelae on the health-related quality of life (HRQOL). Materials and Methods: This is a cross-sectional study. The Arabic version of EORTC QLQ-C30 (version 3) and EORTC QLQ-BR23 questionnaire was administered to a random sample of 172 Egyptian women with breast cancer. One hundred and nineteen patients had modified radical mastectomy (MRM) and 53 had breast conservative surgery (BCS). Results: The mean age was 50.32 years (±standard deviation [SD] = 8.54) with a mean period of 4.75 years (±SD 3.33) from surgery. The global health was poor (28.38 ± 11.7, 95% confidence interval [95% CI]: 30.71). Among the functional scales of QLQ-C30, social functioning scored the highest (87.91 ± 17.92, 95% CI: 91.64) whereas emotional functioning scored the lowest (59.61 ± 24.96, 95% CI: 64.66). The most distressing symptom on the symptom scales of QLQ-C30 was financial impact followed by fatigue and pain (mean: 57.87, 39.43, and 36.44). Using the disease-specific tools, it was found that body image and sexual functioning scored the lowest (mean 74.51 ± 13.21 and 74.45 ± 14.89, 95% CI: 77.27 and 77.55), respectively. On the symptom scale, arm symptoms scored the highest with a mean of 32.35 ± 23.22 (95% CI: 37.19). MRM patients had more favorable global health status and body image among the functional scale (P = 0.011, 0.027) due to social and religious issues. The functional scale was better in BCS with significant role function (P = 0.004). In the symptom scale, fatigue, pain, systemic side effects, and arm symptoms were statistically significant better in the BCS (P = 0.004, 0.006, 0.002, and 0.003, respectively). Conclusion: Egyptian breast cancer survivors reported lower overall global QOL. HRQOL is better in BCS in spite of good global health and body image in MRM.

Allellic HER-2 codon 655 polymorphism and the influence of plasma HER-2 levels in breast cancer Egyptian female patients

Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. Alterations of human epidermal growth factor receptor-2 (HER-2) proto-oncogene have been associated with carcinogenesis and poor prognosis of breast cancers. HER-2 DNA amplification is suggested to be the principal mechanism of HER-2 protein activation. The aim of the study was to clarify the possible association between HER-2 gene polymorphism at codon 655, free plasma HER-2 level, and breast cancer risk. Eighty Egyptian female patients (40 with early breast cancer and 40 with locally advanced breast cancer) were tested for HER-2 genetic polymorphism at codon 655 by restriction fragment length polymorphism–polymerase chain reaction assay. Also, the plasma level of HER-2 was measured using enzyme-linked immunosorbent assay. There was significant increase in mutant G allele frequency among locally advanced group compared to the control group and this conferred 12-fold increased disease risk among the studied group. No significant association could be detected between early breast cancer and HER-2 gene polymorphism. There is a statistically significant increase in the mean plasma HER-2 level among locally advanced breast cancer patients in comparison to the control group suggesting that plasma HER-2 contributes to the development, the higher stage, and dissemination of breast cancer.