Manar Moneer

Purpose: To identify statistical errors and pitfalls in dissertations performed as part of the requirements for the Medical Doctorate (MD) degree at the National Cancer Institute (NCI), Cairo University (CU) to improve the quality of medical research. Methods: A critical assessment of 62 MD dissertations conducted in 3 departments at NCI, CU, between 2009 and 2013 was carried out regarding statistical methodology and presentation of the results. To detect differences in study characteristics over time, grouping was into two periods; 2009-2010 and 2011-2013. Results: Statistical methods were appropriate in only 13 studies (24.5%). The most common statistical tests applied were chi-square, log-rank, and Mann-Whitney tests. Four studies estimated sample size and/or power. Only 37.1% and 38.7% of dissertation results supported aims and answered the research questions, respectively. Most of results were misinterpreted (82.3%) with misuse of statistical terminology (77.4%). Tabular and graphical data display was independently informative in only 36 dissertations (58.1%) with accurate titles and labels in only 17 (27.4%). Statistical tests fulfilled the assumptions only in 29 studies; with evident misuse in 33. Ten dissertations reported non-significance regarding their primary outcome measure; the median power of the test was 35.5% (range: 6-60%). There was no significant change in the characteristics between the time periods. Conclusion: MD dissertations at NCI have many epidemiological and statistical defects that may compromise the external validity of the results. It is recommended to involve a biostatistician from the very start to improve study design, sample size calculation, end points estimation and measures.

BACKGROUND: Epstein-Barr virus (EBV) and human cytomegalovirus (CMV) infections are environmental risk factors affecting the outcome of cancer due to an impairment in the cell-mediated immunity. Therefore, this study aimed to detect the frequency of EBV and CMV DNA and their association with clinical characteristics and outcome of pediatric leukemic patients.METHODS: Samples of 50 immunocompromised pediatric leukemic patients and 30 apparently healthy children were subjected to the amplification of EBV DNA by one version of PCR targeting the Bam H1 W region of the genomic region of EBV, and the amplification of CMV DNA by targeting the CMV UL97 genomic region by a second round PCR. All investigations were performed on WBCs and sera. Results were correlated with the clinical and laboratory characteristics of the disease, and with overall survival.
RESULTS: EBV and CMV DNA were detected in 20 and 54% of leukemic patients, respectively. Nine out of ten patients with EBV DNA (90%) were positive for CMV DNA in their sera. The presence of EBV DNA or CMV DNA was associated with neutropenia and a low total leukocyte count (TLC) (p = 0.02, 0.03, respectively). The presence of severe CMV disease, longer duration of febrile neutropenia, neutropenia, lymphopenia, thrombocytopenia and the presence of EBV DNA in patients' sera were significantly associated with worse overall survival.
CONCLUSION: The detection of CMV disease and EBV DNA is relatively common in leukemic children and is significantly associated with a decline in the overall survival.

BK and JC polyomaviruses (PyV) have been demonstrated to be associated with the pathogenesis of various human cancers. We aimed to investigate the impact of BK and JC polyomavirus infections on several clinical parameters in different human cancers. A total of 150 cancer patients were included in the study (51 patients with solid tumors, 48 patients with lymphomas and 51 patients with leukemias). Amplification of PyV DNA was performed using a semi-nested version of Polymerase chain reaction targeting the T genomic region of PyV. The polyomavirus load was determined using real-time PCR assay. The clinical data were collected. Polyomavirus DNA could be detected in 84 (56%) of 150 of all cancerous patients. The solid tumors had the lowest proportion of JCV (6 (11.8%) of 51), whereas had the highest proportion of JCV (200copies/μl). JCV was more frequent among NHL patients (30%) and absent in HL patients (0%). During follow-up, PyV positivity decreased significantly (p=0.004) in lymphoma patients (n=28). Although PyV positivity decreased significantly from 39% to 7% in 28 of 48 lymphoma patients after treatment, it significantly persisted in leukemic patients after treatment (from 22% to 38%). JC was more frequent among leukemic patients with leukopenia. The presence of JC polyomavirus was more frequent among leukemic patients without any significant impact on their overall survival.

BACKGROUND: Proper surgery with adequate safety margin and adjuvant radiotherapy is the main line of treatment of extremity and trunk soft tissue sarcoma (STS). In spite of improved management, the long term follow up is still not satisfactory.OBJECTIVE: To evaluate long term outcome of STS of extremities and trunk regarding adequacy of resection, recurrence and survival.
PATIENTS AND METHODS: This prospective study included 25 patients with STS involving extremity and trunk. All patients were treated with wide radical excision and had adjuvant irradiation and followed up for a median of 26months.
RESULTS: The mean age was 40.0±15.3years. They were 16 males and 9 females. Eight patients (32%) had positive or close surgical margins. The median overall survival (OS) was 26.5months. In univariate analysis, lower limb tumors, stage III and grade 3 were significantly associated with worse overall survival (OS) (p=0.007, 0.02, and 0.020, respectively) and disease free survival (DFS) (p=0.005, 0.001, and 0.001, respectively). On multivariate analysis the only independent factor that affects the OS and DFS was the stage (p value=0.029, Hazard ratio: 3.64, 95% confidence interval: 1.14-11.61 and p value=0.003, Hazard ratio: 5.75, 95% confidence interval: 1.82-18.18 respectively).
CONCLUSION: Despite adequate surgery and adjuvant irradiation, 5years follow up results of treatment of extremity and trunk soft tissue sarcoma is still poor. This highlights the importance of early detection of small STS in extremity and trunk.

BACKGROUND: Despite the proven benefits, laparoscopic colorectal surgery is still underutilized among surgeons especially in developing countries. Also a steep learning is one of the causes of its limited adoption.OBJECTIVE: To explore the learning curve of single surgeon experience in laparoscopic colectomy and feasibility of implementing a well standardized step by step operative technique to overcome the beginning technical obstacles.
PATIENTS AND METHODS: This prospective study included 50 patients with carcinoma of the left colon and rectum recruited from the department of surgical oncology at National Cancer Institute, Cairo University in the period 2012-2016. All the procedures were performed through laparoscopic approach. Intra and post-operative data were recorded and analyzed.
RESULTS: The mean age was 49.7±10.6years (range: 33-74years). They were 29 males and 21 females. The mean operation time was 180min (range 100-370min), and the mean blood loss was 350ml (60-600ml). Six patients (12%) were converted to a laparotomy. The median lymph nodes harvest was 12 (range 7-25). The mean time of passing flatus after surgery was 2days (1-4days) and the mean time of passing stools was 3.3days (2-5) days. The median hospitalization period after surgery was 4days (3-12). 5 patients (10%) had postoperative morbidity, major morbidity occurred in one patient.
CONCLUSION: Laparoscopic colorectal surgery for colorectal cancer is safe and oncologically sound, standardized well-structured laparoscopic technique masters the procedure even in early learning curve setting.

The diagnosis of a family member with any disease certainly affects the family life in general. Hence, this
study aims at exploring how the diagnosis of a child with cancer affects family life. Additionally, the study
seeks to identify the extent to which the life of family can change when they have a child diagnosed with
cancer. This study uses advanced statistical analysis through conducting a random sampling field study of
(804) individuals, of which (402) were mothers of children diagnosed with cancer (as a case group), and
(402) were mothers whose children’s samples gave negative results when tested for cancer (as a control
group). Through a Questionnaire Form designed to track the extent to which the lives of families covered
by the two study samples (the case group and the control group) have changed, data were collected in 2015,
the researcher used a number of indicators, which she believes to have an effect on family status, to
compare the changes experienced by families in both groups. The 11 indicators used by the study measure
the effects of having a child with cancer in each family individually. Results revealed significant
differences in the values of indicators between the group having a child with cancer and the group whose
children tested negative for cancer before and after diagnosis/examination. A composite indicator
consisting of the previous indicators is developed using Factor Analysis, which calculated the said indicator
based on four factors. These factors are then multiplied by their corresponding weights and aggregated into
the new composite indicator(Family Status Indicator). The indicator was clustered using the K-Mean
Cluster Analysis into 3 clusters, i.e. low, medium, and high. Conclusion: The child cancer has an impact on
the Family Status indicator, demographics and socioeconomic determinants affect the Family Status
indicator like (mother work and Education, Education of the father, Place of Residence,...etc.) after child
examination or disease.

BACKGROUND AND AIM: In recent years, a few of the antibiotic-resistant bacteria, known as ESKAPE pathogens, have been found responsible for serious infections. We investigated the risk factors, and impact of ESKAPE pathogens on course of blood stream infections (BSIs) in cancer patients in comparison to coagulase negative Staphylococci (CoNS).PATIENTS AND METHODS: The data of patients with ESKAPE positive blood cultures at National Cancer Institute, Cairo University were analyzed. Identification and antimicrobial susceptibility of isolates were done using Microscan Walk Away 96.
RESULTS: In a 6month period, ESKAPE pathogens were isolated from non-duplicate blood cultures in 81 episodes of 72 cases of pediatric cancer patients, while CoNS were isolated from 135 blood cultures of 116 patients. The ESKAPE pathogens isolated were Enterobacter spp., methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci in 12%, 23%, 37%, 10%, 9%, and 9% of episodes, respectively. Health-care acquired infections constituted 75% of ESKAPE infections. Duration of episodes and overall mortality were significantly higher in ESKAPE BSIs when compared to CoNS (14.5±7.6 versus 09.9±6.9), and (26% versus 4%); respectively, p value <0.001.
CONCLUSIONS: ESKAPE pathogens were significantly associated with higher rates of morbidity and mortality indicating the need for improving the means of prevention of these types of infections within health care premises. Microbiology laboratories have a role in defining more dangerous infections and rapid diagnostics are required in the era of resistance.

Postoperative sepsis is the leading cause of morbidity and mortality after major surgery, resulting in hefty financial
costs in hospitals all over the world. 40 Fischer rats were injected intra-peritoneally with 0.05 ml Covexin 10 which
contains toxoids from different Clostridial species, 2 weeks prior to caecal ligation and puncture. Another 40
Fischer rats, as a control, underwent caecal ligation and puncture without vaccination. 16 of 40 vaccinated rats
died (40%), peritoneal fluid cultures from the dead rats grew E. coli only, and 36 of 40 control rats died (90%),
peritoneal fluid cultures from the dead rats were: 19 grew E. coli and C. perfringens; 12 grew E. coli,C.
perfringens, and enterococci; 3 grew E. coli only; 1 grew E. coli, and enterocci; and 1 grew no organisms.
Prophylactic vaccination with clostridial toxoids proved effectiveness in preventing anaerobic infection, and reduce
mortality in rats that underwent caecal ligation and puncture; the gold standard model for polymicrobial sepsis.
Currently, a pilot study is underway in which human patients who will undergo major surgery are prophylactically
vaccinated with clostridial toxoids, in an attempt to eradicate postoperative anaerobic sepsis.

BACKGROUND:
For a long time peritoneal neoplasms were considered beyond surgical intervention and beyond cure, till the concept of cytoreductive surgery (CRS) and adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced. However this surgical intervention is technically demanding and associated with considerable postoperative morbidity.
OBJECTIVE:
To describe the surgical strategy in resection of critical sites loaded by heavy tumor deposits and to evaluate short and long term results of CRS and HIPEC, in a cohort of Egyptian patients with pseudomyxoma peritonei (PMP) from appendiceal origin.
PATIENTS AND METHODS:
21 patients with PMP, age ranged from 40 to 63years, 12 males and 9 females. All were recruited from the department of surgery at the National Cancer Institute (NCI), Cairo University over the period from February 2011 to February 2016. They were subjected to CRS and HIPEC with mitomycin-C.
RESULTS:
The median peritoneal carcinoma index (PCI) was 22 (range: 10-39). Optimal cytoreduction (CCR-0/1) was achieved in 19 patients (90.4%) of whom 17 patients (80.9%) had a complete cytoreduction (CCR-0). The median follow up period was 51.5months (range: 0.07-82.3months). The cumulative overall survival was 85.7% while the cumulative disease free survival was 76.9%.
CONCLUSION:
To the best of our knowledge, this is the first study reporting five years postoperative outcome of CRS and HIPEC in Egyptian patients with PMP from appendiceal origin. Our results support that although technically demanding this treatment modality is safe and associated with favorable outcome.

INTRODUCTION: In clinical practice, there is increasing recognition that HER2-positive breast cancer patients are not a homogeneous group. Especially patients with luminal B breast cancers which are now subdivided to more than two groups.AIM OF THE STUDY: The aim of this study is to know the effect of HER2 positivity on luminal breast cancer patients by comparing disease free survival DFS luminal of HER2 positive breast cancer patients with other luminal cases with HER2 negative disease. Also we explored the effect of HER2 positivity on different risk factors for breast cancer.
PATIENTS AND METHODS: We compared the outcome of 25 HER2 positive luminal breast cancer patients with a control group of other luminal operable breast cancer at the same period of time with the same eligibility and exclusive criteria.
RESULTS: Total of 59 operable luminal breast cancer patients were eligible for the study, 25 of them were luminal HER2 positive and the 34 were control group of luminal HER2 negative. We found that HER2 positive luminal breast cancer patients were having more unfavorable risk factors and have more incidence of relapse mainly after 48 months follow-up than other luminal patients: after 24 months follow-up period HER2 positive luminal patients have cumulative DFS of 91% compared with 93% in luminal HER2 negative patients but after 48 months follow-up the difference between the two groups became more obvious as it was 66% for luminal HER2 positive group and 90 % for the control group. High risk patients for luminal HER2 positive breast cancer patients have higher risk of relapse (60% compared with 86%), and this appeared also in other subgroups.
CONCLUSION: HER2 positive luminal breast cancer patients have a higher incidence of relapse compared with other luminal breast cancer, and this difference appear mainly after 48 months of follow-up. High risk patients for luminal HER2 positive breast cancer have higher risk of relapse than high risk patients of other luminal patients.

Purpose: Adjuvant radiation therapy could reduce loco regional failure, but currently has no defined role because of previously reported morbidity. NCI-Cairo routine work is to give adjuvant PORT for locally advanced bladder carcinoma patients. The aim of this work is to re-evaluate this protocol regarding its effect on prognosis and complications. Patients and Method: A retrospective study included 208 patients with pathologically proven bladder cancer who presented to the NCI, Cairo University from 2007-2011. All of them underwent RC with bilateral PLND followed by conventional post-operative radiotherapy in 2 - 6 weeks after surgery for 5000 cGy in 25 fractions, over 5 weeks using 2D technique. Analysis of data from their files was done for the treatment results, prognostic factors and complications. Results: Three years overall survival (OS) and disease free survival (DFS) for the whole group was ~60%, and 54% respectively in favour of the female gender, non-smokers, Squamous cell carcinoma patients, low grade tumours (grade 1 and 2) negative margins, N0, pT2b and early stage group showed the best prognoses. The 3 years metastases free survival (MFS) was ~71%. Only four factors showed a significant relation with the MFS which were the grade, LN status, T-stage and group staging. The local recurrence rate (LRC) at 2 years for the whole group was ~95% and 94% at 3 years. Only surgical margin status and extent of LN dissection had a significant impact on the LRC. Conclusions: Adjuvant radiotherapy shows sustained improvement in the loco regional control, and should be recommended for patients with locally advanced disease especially those with less than 10 dissected lymph nodes and those with positive margins.

Many studies have demonstrated that osteopontin (OPN) contributes functionally to aggressive behaviour in many tumours including breast cancer.

BACKGROUND: Epithelial ovarian cancer (EOC) is the commonest malignancy involving the ovaries. Maximum surgical cytoreduction (MCR) followed by adjuvant taxane-platinum chemotherapy are the standard of care treatments.AIMS: To study treatment outcomes of EOC patients that were maximally cyto-reduced and received adjuvant paclitaxel-carboplatin (PC) chemotherapy.
MATERIALS AND METHODS: This retrospective cohort study included 174 patients with EOC treated at the Egyptian National Cancer Institute between 2006 and 2010. For inclusion, they should have had undergone MCR with no-gross residual followed by adjuvant PC chemotherapy. MCR was total abdominal hysterectomy/bilateral salpingo-oophorectomy [TAH/BSO] or unilateral salpingo- oophorectomy [USO] plus comprehensive staging.
RESULTS: The median age was 50 years. Most patients were married (97.1%), had offspring (92.5%), were postmenopausal (53.4%), presented with abdominal/pelvic pain and swelling (93.7%), had tumors involving both ovaries (45.4%) without extra-ovarian extension i.e. stage I (55.2%) of serous histology (79.9%) and grade II (87.4%). TAH/BSO was performed in 97.7% of cases. A total of 1,014 PC chemotherapy cycles were administered and were generally tolerable with 93.7% completing 6 cycles. Alopecia and numbness were the commonest adverse events. The median follow up period was 42 months. The 2-year rates for disease free survival (DFS) and overall survival (OS) were 70.7% and 94.8%, respectively. The respective 5-year rates were 52.6% and 81.3%. Advanced stage and high-grade were significantly associated with poor DFS and OS (p<0.001). Age >65 years was associated with poor OS (p =0.008). Using Cox-regression, stage was independent predictor of poor DFS and OS. Age was an independent predictor of poor OS.

Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. Aim: Monitoring if a change has occurred in pattern of blood stream infections (BSI) in febrile neutropenic (FN) pediatric cancer patients. Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, and prolonged duration of episodes when compared to previous surveillance, with a p value of <0.001, 0.005, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, 6% in 2011 and 10% in 2006. Conclusion: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and prolonged episodes.

BACKGROUND: Somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene occur frequently in primary brain tumors. Recently theses mutations were demonstrated in acute myeloid leukemia (AML). So far, assessment of these mutations relied on the DNA sequencing technique.AIM OF THE WORK: The aim of this study was to detect somatic mutations in IDH1 gene using mismatched primers suitable for endonuclease based detection, without the need for DNA sequencing, and to estimate its prognostic value, on patients with de novo AML.
METHODS: Residual DNA extracted from pretreatment bone marrow (BM) samples of 100 patients with de novo AML was used. The polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) was adapted to IDH1gene, codon 132 mutations screening.
RESULTS: The frequency of IDH1 mutations was 13%. In the non-acute promyelocytic leukemia group (non-APL), IDH1 mutations were significantly associated with FLT3-ITD negative patients (p=0.03). Patients with IDH1 mutations did not achieve complete remission (CR). There was a trend for shorter overall survival (OS) in patients with IDH1 mutation compared to those with wild type (p=0.08).
CONCLUSION: IDH1 mutations are recurring genetic alterations in AML and they may have unfavorable impact on clinical outcome in adult AML. The PCR-RFLP method allows for a fast, inexpensive, and sensitive method for the detection of IDH1 mutations in AML.

BACKGROUND AND OBJECTIVE: It is almost 40 years since the foundation of the Medical Oncology (MO) Department. We aimed to appraise the clinical research to fulfill the Medical Doctorate (MD) degree in MO at the National Cancer Institute, Cairo University (NCI, CU).METHODS: This review included 62 MD theses containing 66 studies. They were reviewed regarding aims, type of study, clinical trial phase, design and methodology, statistical tests, results, limitations, consent and IRB approval. Theses were grouped into 3 periods: 1970-1989, 1990-1999 and 2000-2008.
RESULTS: Almost 76% of the studies were interventional and 24% were observational. Informed consent and Institutional Review Board approval were mentioned in 18 and 2 studies, respectively. While all studies mentioned the aims, none, clearly mentioned the research question. Outcomes were mainly efficacy followed by safety. Study design was inadequately considered, especially in 70's-80's period (p=0.038). Median sample size and study duration were almost stable through the three periods (p=0.441, 0.354, respectively). Most of the studies used both descriptive and analytical statistical methods. In a descending order, researched cancers were lymphoma, breast, leukemia, liver, urinary bladder, lung and colorectal. The commonest stages researched were IV and III. The number of studies focused on assessing biomarkers, biomarkers plus drugs/procedures, drugs and procedures are 20, 20, 16 and 6, respectively.
CONCLUSION: With time, research within MD theses in MO increased quantitatively and qualitatively. Improvements were noticeable in documentation of study design.

BACKGROUND: Hepatocelluar carcinoma (HCC) is a common cancer worldwide as well as in Egypt with hepatitis B and C, alcohol and aflatoxins being the commonest risk factors. Tamoxifen was initially reported to confer a marginal survival benefit in advanced HCC. However, later reports declined any benefit.OBJECTIVE: To study the impact of tamoxifen on overall survival (OS) compared to best supportive care (BSC) in Egyptian patients with advanced HCC.
METHODS: This retrospective matched-cohort study was conducted at Tanta Cancer Center (TCC), Egypt where 116 advanced HCC cases treated with tamoxifen were compared to TNM stage and Child-Pugh class matched 116 HCC cases who received BSC.
RESULTS: The median OS in the tamoxifen group was 9.3 months (95% confidence interval [CI], 6.7-11.9 months) compared to 8.7 months (95%CI, 6.8-10.6) in the BSC group (p=0.758). With univariate analyses, it was shown that absence of fatigue, Child-Pugh class A, single tumors, less advanced tumors (T2), and absence of metastases (M0), had significantly better OS than their counterparts. Multivariate analysis showed that absence of fatigue, Child-Pugh class A and T2 tumors were independent prognostic factors affecting OS. Tamoxifen produced partial response and clinical stabilization in one% and 16% of cases, respectively. The median PFS with tamoxifen was 7.2 months (95%CI, 5.2-9.5).
CONCLUSIONS: Tamoxifen did not show any OS advantage in Egyptian patients with advanced HCC. Use of this drug is discouraged.

INTRODUCTION: Female germ cell tumors (GCTS) are rare tumors that carry a good prognosis.AIM: To report the experience of the Egyptian National Cancer Institute (ENCI) in managing female GCTs.
METHODS: This retrospective study included 19 females with ovarian GCTs presenting to the ENCI between 2006 and 2010.
RESULTS: The median age was 23years. Ovaries were the primary site in all patients. Dysgerminoma and teratoma were the predominant pathologies followed by mixed GCT in females. Unilateral ovariectomy or ovarian tumorectomy were the classic surgical procedures with R0 resection being feasible in most cases. Surveillance was adopted in six patients with stage I disease. Chemotherapy was administered in 63% of ovarian GCTs with BEP being the commonest regimen with reasonable tolerability and good response rates. The median OS and EFS were not reached. The projected 5-year OS rate was 93.8%. Both OS and EFS were better in patients responding to chemotherapy than non-responders (p<0.002). Stage of disease did not significantly affect OS or EFS.
CONCLUSIONS: Female GCTs rarely affect Egyptian females. They have good prognosis.

BACKGROUND: Breast illumination was suggested as a simple method for breast cancer screening. BreastLight is a simple apparatus for this purpose.OBJECTIVE: To evaluate the diagnostic performance of BreastLight as a screening tool of breast cancer in comparison to mammography and histopathology.
MATERIALS AND METHODS: This hospital-based cross sectional study was conducted in the mammography unit of the radiodiagnosis department at National Cancer Institute, Cairo University. All participants were subjected to breast examination with the BreastLight tool, mammography and ultrasonography. Suspicious cases were biopsied for histopathological examination which is considered as a gold standard.
RESULTS: The mean age of the participants was 46.3±12.4 years. Breast illumination method had sensitivity, specificity, positive predictive value, negative predictive value and total accuracy of 93.0%, 73.7%, 91.4%, 77.8% and 88.2%, respectively in detection of breast cancer.
CONCLUSIONS: Breast illumination method with BreastLight apparatus is a promising easy-to-use tool to screen for breast cancer suitable for primary health care physician or at-home use. It needs further evaluation especially in asymptomatic women.

BACKGROUND: The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SNP) in codon Arg72Pro of P53 results in impairment of the tumor suppressor activity of the gene. A similar effect is caused by a SNP in codon 31 of P21. In contrast, a SNP in position 309 of MDM2 results in increased expression due to substitution of thymine by guanine. All three polymorphisms have been associated with increased risk of tumorigenesis.AIM OF THE STUDY: We aimed to study the prevalence of SNPs in the P53 pathway involving the three genes, P53, P21 and MDM2, among acute myeloid leukemia (AML) patients and to compare it to apparently normal healthy controls for assessment of impact on risk.
RESULTS: We found that the P21 ser31arg heterozygous polymorphism increases the risk of AML (P value=0.017, OR=2.946, 95% CI=1.216-7.134). Although the MDM2 309G allele was itself without affect, it showed a synergistic effect with P21 ser/arg polymorphism (P value=0.003, OR= 6.807, 95% CI= 1.909-24.629). However, the MDM2 309T allele abolish risk effect of the P21 polymorphic allele (P value= 0.71). There is no significant association of P53 arg72pro polymorphism on the risk of AML.
CONCLUSION: We suggest that SNPs in the P53 pathway, especially the P21 ser31arg polymorphism and combined polymorphisms especially the P21/ MDM2 might be genetic susceptibility factors in the pathogenesis of AML.

BACKGROUND: PubMed is a free web literature search service that contains almost 21 millions of abstracts and publications with almost 5 million user queries daily. The purposes of the study were to compare trends in PubMed-indexed cancer and biomedical publications from Egypt to that of the world and to predict future publication volumes.METHODS: The PubMed was searched for the biomedical publications between 1991 and 2010 (publications dates). Affiliation was then limited to Egypt. Further limitation was applied to cancer, human and animal publications. Poisson regression model was used for prediction of future number of publications between 2011 and 2020.
RESULTS: Cancer publications contributed 23% to biomedical publications both for Egypt and the world. Egyptian biomedical and cancer publications contributed about 0.13% to their world counterparts. This contribution was more than doubled over the study period. Egyptian and world's publications increased from year to year with rapid rise starting the year 2003. Egyptian as well as world's human cancer publications showed the highest increases. Egyptian publications had some peculiarities; they showed some drop at the years 1994 and 2002 and apart from the decline in the animal: human ratio with time, all Egyptian publications in the period 1991-2000 were significantly more than those in 2001-2010 (P < 0.05 for all). By 2020, Egyptian biomedical and cancer publications will increase by 158.7% and 280% relative to 2010 to constitute 0.34% and 0.17% of total PubMed publications, respectively.
CONCLUSIONS: The Egyptian contribution to world's biomedical and cancer publications needs significant improvements through research strategic planning, setting national research priorities, adequate funding and researchers' training.

PURPOSE: With the increasing emergence of multiresistant pathogens, better understanding of these infections is necessary. The aim of the present study was to evaluate the risk factors associated with isolating a multiresistant organism (MRO) from a positive blood culture in pediatric cancer patients with febrile neutropenia (F&N), and to study its impact on clinical course and outcome of febrile episodes.

PATIENTS AND METHODS: The association between MRO with underlying malignancy, age, disease status, hospitalization during episode, absolute neutrophil count, absolute monocyte count, clinical foci of infection, and pathogens isolated was assessed in bacteremic pediatric cancer patients. The MRO phenotype was defined as diminished susceptibility to ≥3 of the broad spectrum antibody classes.

RESULTS: Among 239 episodes of blood stream infections (BSI), Gram-positive, and Gram-negative organisms were detected in 180 (75%), and 59(25%) episodes, respectively; with 38% of isolates showing multiresistance (n = 92). Significant risk factors (P < 0.05) for MRO were hospitalization, Gram-negative organisms, presence of clinical focus of infection, reduced ANC, prolonged duration of neutropenia, and previous intake of antibiotics. Of the episodes with prolonged duration of fever extending for more than 7 days 62% (64|93) were associated with a multiresistant phenotype, while it accompanied 72% (18|25) of the cases with an unfavorable outcome; P-value <0.001.

CONCLUSION: Isolation of MRO is more likely to be associated with a prolonged course and an unfavorable outcome. Continuous multidisciplinary surveillance of BSI is warranted to develop strategies for antimicrobial resistance control.

OBJECTIVE: To assess the epidemiological and clinico-pathological features, surgical and reconstructive techniques, adjuvant treatments and clinical outcome of breast carcinoma in males (BCM) at the Egyptian National Cancer Institute (NCI).PATIENTS AND METHODS: Thirty-two males with breast carcinoma presented to NCI between January 2000 and December 2002. They were evaluated by complete history, physical examination, laboratory and radiological investigations.
RESULTS: Median age was 59 years. Left sided and retroareolar breast lumps were the commonest presentations. Grade II tumors positive for hormone receptors were very common. Stages I, II, III and IV of the disease were encountered in 6.2%, 34.4%, 34.4% and 25.0% of patients, respectively. Curative surgery was done in 22 patients; they received adjuvant hormonal therapy, chemotherapy and radiotherapy in 22, 16 and 10 patients, respectively. Eight metastatic patients were treated with palliative measures. Surgery was done in 25 patients; the most common procedure was modified radical mastectomy (40.6%). Primary closure was feasible in 17 patients (68%), local flaps were needed in 4 cases (16%), while myocutaneous flap was done in 3 cases (12%). The commonest complication was the development of seroma (9 cases). The overall survival (OS) at 5 years was 65.4%. The disease free survival (DFS) at 5 years was 53.9%. Stage and curative surgery significantly affected OS, while type of surgery was the only variable significantly affecting DFS.
CONCLUSION: Male breast carcinoma occurs at older ages than females, usually in advanced stage. This necessitates directing attention of males and awareness on the prevalence and risk factors for this disease.