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Ashraf Omar,1 Ahmed Kaseb,2 Tamer Elbaz,1 Mohamed El-Kassas,3 Amr El Fouly,3 Abdel Fatah Hanno,4 Ahmed El Dorry,5 Ahmed Hosni,6 Amr Helmy,7 Amr S Saad,8 Ashwaq Alolayan,9 Basem Elsayed Eysa,10 Emad Hamada,11 Hamdy Azim,11 Hany Khattab,12 Hesham Elghazaly,8 Hesham Tawfik,13 Hisham Ayoub,14 Hussein Khaled,11 Ibtessam Saadeldin,11 Imam Waked,15 Eman MF Barakat,16 Mahmoud El Meteini,17 Mohamed Hamed Shaaban,6 Mohamed EzzElarab,10 Mohamed Fathy,17 Mohamed Shaker,5 Mohamed Sobhi,5 Mohamed Kamal Shaker,16 Mohamed ElGharib,5 Mohammed Abdullah,11 Mohesn Mokhtar,11 Mostafa Elshazli,18 Omar Mohamed Khaleil Heikal,14 Osama Hetta,5 Reda Mahmoud ElWakil,16 Sameh Abdel Wahab,5 Samir Shehata Eid,19 Yousri Rostom20 On behalf of the Egyptian Liver Cancer Committee Study Group1Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt; 2Department of Gastrointestinal Medical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA; 3Department of Endemic Medicine, Faculty of Medicine, Helwan University, Cairo, Egypt; 4Department of Gastroenterology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 5Department of Interventional Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Interventional Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 7Department of Surgery, National Liver Institute Menoufia University, Menoufia, Egypt; 8Department of Oncology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 9Department of Oncology, National Guard Hospital, Riyadh, Saudi Arabia; 10Department of Gastroenterology, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt; 11Department of Oncology, Faculty of Medicine, Cairo University, Cairo, Egypt; 12Department of Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt; 13Department of Oncology, Faculty of Medicine, Tanta University, Tanta Egypt; 14Department of Gastroenterology, Military Medical Academy, Cairo, Egypt; 15Department of Gastroenterology, Menoufia Liver Institute, Menoufia, Egypt; 16Department of Gastroenterology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 17Department of Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 18Department of Surgery, Faculty of Medicine, Cairo University, Cairo, Egypt; 19Department of Oncology, Faculty of Medicine, Assiut University, Assiut, Egypt; 20Department of Oncology, Faculty of Medicine, Alexandria University, Alexandria, EgyptCorrespondence: Ashraf Omar, Department of Gastroenterology, Faculty of Medicine, Cairo University, Cairo, Egypt, Email abdelazizashraf@hotmail.comAbstract: Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.Keywords: hepatocellular carcinoma, clinical recommendations, Egyptian society of liver cancer, hepatitis c virus, Egypt, guidelines

Thrombophilia is now considered a multi-causal condition, with interplay of acquired genetic risk factors. In order to estimate the frequency of the factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in the Jordanian population, we screened 200 healthy Jordanian individuals. 40% were females. Mean age was 32.1 years for males and 30.0 years for female participants. A PCR method detected 15.0% factor V Leiden (87% heterozygous, 13% homozygous), 2% prothrombin G20210A (100% heterozygous), and 24% MTHFR C677T (67% heterozygous, 33% homozygous). We conclude that the prevalence of factor V Leiden and MTHFR C677T is elevated in this population of Jordanians. However the incidence of G20210A is relatively low. Quantification of these genetic thrombosis risk factors in various populations will contribute to a better understanding of the interaction of genetic and environmental risk factors. [ABSTRACT FROM AUTHOR]

Background: Vestibular schwannoma (VS), also known as acoustic neuroma, is a benign, well-encapsulated, and slow-growing tumor that originates from Schwann cells, which form the myelin sheath around the vestibulocochlear nerve (VIII cranial nerve). The surgical treatment of this condition presents a challenging task for surgeons, as the tumor's location and size make it difficult to remove without causing damage to the surrounding structures. In recent years, fluorescein sodium (FS) has been proposed as a tool to enhance surgical outcomes in VS surgery. This essay will provide an analytical comparison of the use of FS in VS surgery, evaluating its benefits and limitations and comparing surgical outcomes with and without FS-assisted surgery., Methods: In a retrospective study conducted at San Filippo Neri Hospital, we examined VS cases that were operated on between January 2017 and December 2023. The patients were divided into two groups: group A, which consisted of patients who underwent surgery without the use of FS until January 2020 (102 cases), and group B, which included patients who underwent surgery with FS after January 2020 (55 cases). All operations were performed using the retrosigmoid approach, and tumor size was classified according to the Koos, et al. classification system. The extent of surgical removal was evaluated using both the intraoperative surgeon's opinion and postoperative MRI imaging. Preoperatively and postoperatively, facial nerve function and hearing were assessed. In group B, FS was used to assist the surgical procedures, which were performed using a surgical microscope equipped with an integrated fluorescein filter. Postoperative clinical and MRI controls were performed at six months and annually, with no patients lost to follow-up., Results: This study investigated the impact of intraoperative fluorescein exposure on tumor resection and clinical outcomes in patients with VS. The study found a statistically significant difference in the tumor resection rates between patients who received fluorescein intraoperatively ( p = 0.037). Further analyses using the Koos classification system revealed a significant effect of fluorescein exposure, particularly in the Koos 3 subgroup ( p = 0.001). Notably, no significant differences were observed in hearing loss or facial nerve function between the two groups. A Spearman correlation analysis revealed a positive correlation between tumor size and Koos, age, and size, but no significant correlation was found between facial nerve function tests., Conclusions: FS-assisted surgery for VS may potentially enhance tumor resection, allowing for more comprehensive tumor removal.

Accumulating evidence has indicated that immune regulatory cells are involved in the establishment of the anti-tumor activity, however; the role of regulatory B cells (B-regs) in breast cancer (BC) remains unclear. This study intended to assess the frequency of peripheral B-regs phenotypes in patients with BC, and to determine the relation between these phenotypes and the patient's clinicopathological characters. The expressions of the immune cell populations were analyzed by four-color flow cytometry in 40 naïve BC patients and 10 age-matched apparently healthy individuals as controls attending the department of Clinical Oncology and Nuclear Medicine at Assiut University Hospitals. The percentages of B-regs phenotypes CD19+IL10+ and CD19+CD24hiCD27+IL10+ were higher in BC patients than in the controls. The percentage of CD19+IL10+ B cells phenotype was significantly associated with the HER-2 expression levels, T, and N stages of BC. In conclusion, high percentage of B-regs phenotypes CD19+IL10+ and CD19+CD24hiCD27+IL10+ in BC patients indicates a possible role in immune suppression during the development of BC., (Copyright© by the Egyptian Association of Immunologists.)

Interleukin-35 (IL-35), is a recently identified cytokine that belongs to the IL-12 family, it is a potent anti-inflammatory and immunosuppressive cytokine which was first recognized to be produced by regulatory T cells (Tregs) cells, and recently was found to be produced by regulatory B cells (Bregs). The study aimed at determining whether plasma levels of IL-35 are associated with clinical characteristics of breast cancer (BC) patients. The study included 40 patients with breast cancer (BC), and 10 matched controls. The IL-35 cytokine was measured in plasma using ELISA. Results showed that plasma IL-35levels were significantly higher in BC than healthy controls (P˂ 0.05), and were significantly associated with BC grade 2 and HER-2 over expression level "3+", suggesting that plasma IL-35 levels may be associated with the development and progression of BC., (Copyright© by the Egyptian Association of Immunologists.)

The risk of thrombosis in individuals with rare compound thrombophilias, homozygous factor V Leiden (FVL) plus heterozygous prothrombin G20210A (PTM), homozygous PTM plus heterozygous FVL, and homozygous FVL plus homozygous PTM, is unknown. We identified, worldwide, individuals with these compound thrombophilias, predominantly through mailing members of the International Society on Thrombosis and Haemostasis. Physicians were sent a clinical questionnaire. Confirmatory copies of the genetic results were obtained. One hundred individuals were enrolled; 58% were female. Seventy-one individuals had a venous thrombosis (includes superficial and deep vein thrombosis, and pulmonary embolism), 4 had an arterial thrombosis and 6 had both. Nineteen individuals had never had a thrombotic event. Thrombosis-free survival curves demonstrated that 50% of individuals had experienced a thrombotic event by 35 yrs of age, while 50% had a first venous thromboembolic event (VTE; includes all venous thrombosis except superficial thrombosis) by 41 yrs of age; 38.2% of first VTEs were unprovoked. 37% of patients had at least one VTE recurrence. Seventy percent of first pregnancies carried to term and not treated with anticoagulation were thrombosis-free. In conclusion, patients with these rare compound thrombophilias are not exceedingly thrombogenic, even though they have a substantial risk for VTE., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Genetic and environmental factors interact in determining the risk of venous thromboembolism (VTE). The risk associated with the polymorphic variants G1691A of factor V (Factor V Leiden, FVL), G20210A of prothrombin (PT20210A) and C677T of methylentetrahydrofolate reductase (C677T MTHFR) genes has been investigated in many studies. We performed a pooled analysis of case-control and cohort studies investigating in adults the association between each variant and VTE, published on Pubmed, Embase or Google through January 2010. Authors of eligible papers, were invited to provide all available individual data for the pooling. The Odds Ratio (OR) for first VTE associated with each variant, individually and combined with the others, were calculated with a random effect model, in heterozygotes and homozygotes (dominant model for FVL and PT20210A; recessive for C677T MTHFR). We analysed 31 databases, including 11,239 cases and 21,521 controls. No significant association with VTE was found for homozygous C677T MTHFR (OR: 1.38; 95 % confidence intervals [CI]: 0.98-1.93), whereas the risk was increased in carriers of either heterozygous FVL or PT20210 (OR = 4.22; 95 % CI: 3.35-5.32; and OR = 2.79;95 % CI: 2.25-3.46, respectively), in double heterozygotes (OR = 3.42; 95 %CI 1.64-7.13), and in homozygous FVL or PT20210A (OR = 11.45; 95 %CI: 6.79-19.29; and OR: 6.74 (CI 95 % 2.19-20.72), respectively). The stratified analyses showed a stronger effect of FVL on individuals ≤ 45 years (p value for interaction = 0.036) and of PT20210A in women using oral contraceptives (p-value for interaction = 0.045). In this large pooled analysis, inclusive of large studies like MEGA, no effect was found for C677T MTHFR on VTE; FVL and PT20210A were confirmed to be moderate risk factors. Notably, double carriers of the two genetic variants produced an impact on VTE risk significantly increased but weaker than previously thought.

Autosomal recessive Ellis-van Creveld syndrome and autosomal dominant Weyer acrodental dysostosis are allelic conditions caused by mutations in EVC or EVC2. We performed a mutation screening study in 36 EvC cases and 3 cases of Weyer acrodental dysostosis, and identified pathogenic changes either in EVC or in EVC2 in all cases. We detected 40 independent EVC/EVC2 mutations of which 29 were novel changes in Ellis-van Creveld cases and 2 were novel mutations identified in Weyer pedigrees. Of interest one EvC patient had a T>G nucleotide substitution in intron 7 of EVC (c.940-150T>G), which creates a new donor splice site and results in the inclusion of a new exon. The T>G substitution is at nucleotide +5 of the novel 5' splice site. The three Weyer mutations occurred in the final exon of EVC2 (exon 22), suggesting that specific residues encoded by this exon are a key part of the protein. Using murine versions of EVC2 exon 22 mutations we demonstrate that the expression of a Weyer variant, but not the expression of a truncated protein that mimics an Ellis-van Creveld syndrome mutation, impairs Hedgehog signal transduction in NIH 3T3 cells in keeping with its dominant effect.

Congenital bleeding disorders comprise a heterogeneous group of diseases that reflect abnormalities of blood vessels, coagulation proteins, and platelets. A 14-year retrospective study (1991-2005) was conducted for patients referred to the coagulation section of the Hematology Department (King Hussein Medical Center, Amman, Jordan), who had suffered from bleeding tendencies to assess the prevalence of bleeding disorders among Jordanians and to describe their clinical manifestations. Four hundred and three patients matched our criteria. All patients were screened with routine coagulation assays and a complete blood cell count; a factor assay was performed if indicated by the results of the screening assays. A total of 168 patients (41.6%) were diagnosed with a bleeding disorder caused by a factor deficiency, of which 17.1% were described as hemophilia A (n=69), 6.2% were described as vWD (n=25), and 4.2% were described as hemophilia B (n=17). A subset of the total patient population comprising 14.1% of the patients were diagnosed with a Rare Inherited Coagulation Deficiency (RICD), where 4.0% were FX deficient (n=16), 3.7% were FVII deficient (n=15), 3.7% were FV deficient (n=15), 2.5% were FXI deficient (n=10), and 0.2% were diagnosed with afibrinogenemia (n=1).

Background: The objective of this study was to determine the incidence of undiagnosed thrombophilic factors and its relation to IVF and embryo transfer failure in women who have had three or more previous IVF-embryo transfer cycles., Methods: The study group comprised of 90 consecutive women with three or more previously failed IVF-embryo transfer cycles (group A). Two control groups were enrolled: group B (n=90) included women who have had successful pregnancy after their first IVF-embryo transfer cycle, and group C (n=100) included women who conceived spontaneously with at least one uneventful pregnancy and no previous history of miscarriage. All women were tested for the presence of inherited [factor V Leiden (FVL) mutation, prothrombin mutation, methylenetetrahydrofolate reductase (MTHFR) mutation and deficiencies in proteins S and C and antithrombin III] or acquired (lupus anticoagulant and anticardiolipin) thrombophilic factors., Results: An increase in the incidences of FVL, MTHFR and antiphospholipid antibodies was found in the study group compared with the two control groups. At least one inherited or acquired thrombophilic factor was detected in 68.9% of women with repeated IVF failure compared with 25.6 and 25% in the groups B and C, respectively (P<0.01). Combined thrombophilia (two or more thrombophilic factors) was significantly higher in women who have had repeated IVF failure as compared with the two control groups (35.6 versus 4.4 and 3%) (P<0.0001)., Conclusion: Thrombophilia has a significant role in IVF-embryo transfer implantation failure. Women with repeated IVF-embryo transfer failure should be screened for thrombophilia.

Venous thromboembolism develops as the result of multiple interactions between non-genetic and genetic risk factors. In order to estimate the frequency of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in Jordanian thrombotic patients, we studied 594 patients admitted to the King Hussein Medical Center for thrombophilia assessment. Polymerase chain reaction detected 25.7% (20.7% heterozygous, 5% homozygous), 6% (5.8% heterozygous, 0.2% homozygous) and 31.7% (25% heterozygous, 6.7% homozygous) for factor V Leiden, prothrombin G20210A and MTHFR C677T mutations, respectively. A one-stage clotting assay was used to measure prothrombin activity. None of the prothrombin G20210A mutant patients had high prothrombin activity. The high prevalence found among our study group of factor V Leiden and prothrombin G20210A confirms the importance of thrombophilia screening for patients with venous thrombosis with family history and those with additional risk factors. On the contrary, the high prevalence of the MTHFR C677T mutation among arterial thrombosis patients shows its importance in screening in arterial thrombosis patients. These results, which are close to the prevalence found by other studies in the region, suggests that the Eastern Mediterranean region is probably the area of origin of these mutations, especially factor V Leiden. The knowledge of these frequencies in the Middle East region through population-based studies will contribute to a better understanding of the interaction between genetic and environmental risk factors underlying the mentioned mutations.

This study investigated two patients with Rh chimerism: patient A, a healthy individual, and patient B with myelofibrosis. Flow cytometry studies showed two red blood cell populations of Rh phenotypes R1r and rr at percentages of about 25% and 75% respectively. Normal RhD transcript sequences were found following RT-PCR. Genomic DNA (gDNA) showed normal exon, intron, GATA regions and exon/intron boundary sequences except for a single base change in intron 7 (C --> A) of exon 7 in patient A. The major change found in both patients was the absence of RHD exon 9 DNA in gDNA isolated from peripheral blood. These findings suggest a somatic mutation, probably in a stem cell common to the myeloid lineage of both patients, and indicate that patient A may undergo malignant transformation in the future.

Hereditary thrombophilia is caused by various inherited disorders. Most lead to a familial tendency to recurrent venous, not arterial, thrombosis, usually at a young age, and with spontaneous onset. Most of the genetic defects known today affect the function of natural anticoagulant pathways, in particular, the protein C system. In this study, 602 (265 female, 337 male) patients with suspected thrombosis, arterial or venous, were referred to King Hussein Medical Center in Amman, Jordan. The prevalence of hereditary deficiencies of antithrombin (AT), protein S (PS), and protein C (PC) were studied over a seven-year period (1993-2000). Activated protein C (APC-R) resistance subjects were studied over four years (1996-2000). The mean age was 30 years in females and 42 years in males. A diagnosis was established in 22.4% (n = 135) of the subjects (20.3% venous, 2.1% arterial). Protein C deficiency was found in 3.8%, protein S deficiency in 2.3% and antithrombin deficiency in 1.4% of our sample group. An APC-R problem was seen in 23.0% (n = 89) of the surveyed population. Out of the APC-R patients, 75.0% had the DNA analysis of a factor V Leiden mutation present. Of the subjects found to have the mutation 87.0% were heterozygous and 13.0% were homozygous. These results confirm that APC-R, as a result of factor V Leiden mutation, is the most prevalent cause of thrombosis, and thrombophilia is related to venous, not arterial, thrombosis.