Optimal Localization of a Novel Shifted 1T-Ring Based Microwave Ablation Probe in Hepatocellular Carcinoma.

OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the most dangerous, and fatal cancers. Thermal ablation proved its power as the best treatment method for HCC. In microwave thermal ablation, microwave probes are used to generate electromagnetic waves (EMW) at microwave (MW) frequency 2.45 GHz. In this paper, the design/model of a novel microwave ablation probe, namely a single slot with a shifted 1T-ring probe is presented for HCC therapy. METHODS: A Finite Element Method (FEM) is employed to model the probe and the hepatic tumor liver tissues. The relation between the tip of probe position and the center of the hepatic tumor was studied to determine the best probe location at which a minimum MW power is required to ablate the entire tumor tissues with the smallest damage in the nearby healthy tissues to the tumor. RESULTS: The results indicated that the ablated part of the tissues varies depending on the MW probe type, the amount of used power, the location of the probe, and the exposure time. Hepatic tumors' diameters from 2-5cm were studied. CONCLUSION: It was shown that the proposed SSS 1T-ring (single slot with shifted 1T-ring) probe provided the best ablation performance when the probe's tip placed below the tumor's center by 11 mm, which achieved 100% damage in the tumor tissues using 6 W power for 10 minutes. SIGNIFICANCE: When the probe's tip is located at the center of the tumor, the ablation rate was 73.45% in the tumor tissues under the same conditions.

Colored Video Analysis in Wireless Capsule Endoscopy: A Survey of State-of-the-Art.

Wireless Capsule Endoscopy (WCE) is a highly promising technology for gastrointestinal (GI) tract abnormality diagnosis. However, low image resolution and low frame rates are challenging issues in WCE. In addition, the relevant frames containing the features of interest for accurate diagnosis only constitute 1% of the complete video information. For these reasons, analyzing the WCE videos is still a time consuming and laborious examination for the gastroenterologists, which reduces WCE system usability. This leads to the emergent need to speed-up and automates the WCE video process for GI tract examinations. Consequently, the present work introduced the concept of WCE technology, including the structure of WCE systems, with a focus on the medical endoscopy video capturing process using image sensors. It discussed also the significant characteristics of the different GI tract for effective feature extraction. Furthermore, video approaches for bleeding and lesion detection in the WCE video were reported with computer-aided diagnosis systems in different applications to support the gastroenterologist in the WCE video analysis. In image enhancement, WCE video review time reduction is also discussed, while reporting the challenges and future perspectives, including the new trend to employ the deep learning models for feature Learning, polyp recognition, and classification, as a new opportunity for researchers to develop future WCE video analysis techniques.

The Association Between Body Mass Index and Dental Caries: Cross-Sectional Study.

BACKGROUND: Obesity is a growing health-related problem worldwide. Both obesity and dental caries are important health issues with multifactorial aspects. Some studies have shown an association between body mass index (BMI) and caries in childhood/adolescence but limited data about such an association are available in adults. The primary goal of this study was to assess the prevalence of dental caries and its relationship to BMI. METHODS: We conducted a cross-sectional study at Taif University Outpatient Clinic, for adults who had a visit to the dental clinic. Baseline characteristics were obtained by the participating physician. The decayed, missing, and filled teeth (DMFT) index was used to determine the prevalence of dental caries. Information about healthy eating, smoking, exercise, sleep patterns, media consumption, and brushing habits were collected. RESULTS: A total of 385 patients were enrolled with a mean age of 28.39 years, 72.8% were male, mean DMFT index score was 6.55, and 85.5% reported brushing their teeth at least once daily. Of the participants, 55.3% were either overweight or obese, and 42.2% demonstrated a high prevalence of dental caries with no significant difference in BMI when compared to the low dental caries group. CONCLUSIONS: A high prevalence of overweight/obesity and dental caries was observed among the participants. After controlling for potential confounders like smoking and brushing habits, significant positive correlation between BMI and DMFT was observed.

Methylation of multiple genes in hepatitis C virus associated hepatocellular carcinoma.

We studied promoter methylation (PM) of 11 genes in Peripheral Blood Lymphocytes (PBLs) and tissues of hepatitis C virus (HCV) associated hepatocellular carcinoma (HCC) and chronic hepatitis (CH) Egyptian patients. The present study included 31 HCC with their ANT, 38 CH and 13 normal hepatic tissue (NHT) samples. In all groups, PM of APC, FHIT, p15, p73, p14, p16, DAPK1, CDH1, RARß, RASSF1A, O(6)MGMT was assessed by methylation-specific PCR (MSP). APC and O6-MGMT protein expression was assessed by immunohistochemistry (IHC) in the studied HCC and CH (20 samples each) as well as in a different HCC and CH set for confirmation of MSP results. PM was associated with progression from CH to HCC. Most genes showed high methylation frequency (MF) and the methylation index (MI) increased with disease progression. MF of p14, p73, RASSF1A, CDH1 and O(6)MGMT was significantly higher in HCC and their ANT. MF of APC was higher in CH. We reported high concordance between MF in HCC and their ANT, MF in PBL and CH tissues as well as between PM and protein expression of APC and O(6)MGMT. A panel of 4 genes (APC, p73, p14, O(6)MGMT) classifies the cases independently into HCC and CH with high accuracy (89.9%), sensitivity (83.9%) and specificity (94.7%). HCV infection may contribute to hepatocarcinogenesis through enhancing PM of multiple genes. PM of APC occurs early in the cascade while PM of p14, p73, RASSF1A, RARB, CDH1 and O(6)MGMT are late changes. A panel of APC, p73, p14, O6-MGMT could be used in monitoring CH patients for early detection of HCC. Also, we found that, the methylation status is not significantly affected by whether the tissue was from the liver or PBL, indicating the possibility of use PBL as indicator to genetic profile instead of liver tissue regardless the stage of disease.

Epstein-Barr virus and breast cancer: epidemiological and molecular study on Egyptian and Iraqi women.

BACKGROUND AND PURPOSE: The role of Epstein-Barr virus (EBV) in breast carcinogenesis is still controversial. Unraveling this relationship is potentially important for better understanding of breast cancer etiology, early detection and possibly prevention of breast cancer. The aim of the current study is to unravel the association between EBV and primary invasive breast cancer (PIBC) in two different Arab populations (Egyptian and Iraqi women). PATIENTS AND METHODS: The study was done on paraffin-embedded tissues of 40 Egyptian and 50 Iraqi patients with PIBC in addition to 20 normal breast tissues as controls for each group. Both controls and neoplastic tissues were assessed for the expression of EBV genes and proteins (EBNA-1, LMP-1, and EBER) as well as CD21 marker by immunohistochemistry (IHC), in situ hybridization (ISH) and PCR techniques. RESULTS: Our gold standard for EBV reactivity in breast cancer cases was positivity of both EBNA1 by PCR and EBER by in situ hybridization. EBV was detected in 18/40 (45%) and 14/50 (28%) of Egyptian and Iraqi women; respectively where p=0.073, compared to 0/20 (0%) of their control groups (p<0.05). Regarding the association between EBV positivity and tumor grade, there was not any statistical significant difference between EBV presence and tumor grade in both populations where p=0.860 and p=0.976 and the calculated rank biserial correlation coefficient was 0.114 and 0.269 for Egyptian and Iraqi women respectively. CONCLUSION: Our findings show that EBV might act as a promoter for the development of PIBC and it might contribute to increased tumor aggressiveness in Egyptian and Iraqi patients.

The role of cyclins and cyclin dependent kinases in development and progression of hepatitis C virus-genotype 4-associated hepatitis and hepatocellular carcinoma.

UNLABELLED: Altered cell cycle regulatory genes expression contributes to HCV-associated liver disease. We sought to assess the role of cyclins and cyclin dependent kinases (CDKs) in HCV-associated CH and HCC. Aberrant expression of cyclins A, E, D1, CDK2 and CDK4 was assessed by immunohistochemistry and differential PCR in HCV-associated CH and HCC with pericarcinomatous foci (PCF). S phase fraction (SPF) was determined by flow cytometry. Results were correlated with overall survival (OS) in HCC patients. In HCC, cyclins A, E, D1, CDK2 and CDK4 protein overexpression was detected in 52.8%, 52.8%, 69%, 47% and 58% compared to 36.1%, 33%, 56%, 27.8%, 55.6% for CH and 36.1%, 27%, 30.6%, 27%, 50% for PCF. Gene amplification was detected in 38.9%, 33% 66%, 33%, 44% of HCC compared to 27.8%, 25%, 44%, 27.8%, 36% in CH and 25%, 22.2%, 38.9%, 27%, 33% in PCF. A significant difference was reported between HCC, CH, NHT regarding cyclins A, E, D1, CDK2 (p=0.007, p=0.002, p=0.047, p=0.002) protein expression (ADD) and cyclin D1 amplification (p=0.009). Cyclins A, E, CDK2 expression was associated with fibrosis in CH (p=0.004, p=0.02, p=0.012). Reduced OS was (ADD) associated with cyclin D1 and cyclin A, grade, stage and metastasis (p=0.001, p=0.02, p=0.018, p=0.01, p=0.001). CONCLUSIONS: Increased cyclins A, E, D1, CDK2 and CDK4 expression is important for HCV-associated CH and HCC. Cyclin D1 and cyclin A are prognostic biomarkers associated with reduced OS in HCC. Cyclin D1 aberration could identify high risk groups of CH patients prone to develop HCC.

Serum levels of soluble Fas, soluble tumor necrosis factor-receptor II, interleukin-2 receptor and interleukin-8 as early predictors of hepatocellular carcinoma in Egyptian patients with hepatitis C virus genotype-4.

BACKGROUND: Liver disease progression from chronic hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) is associated with an imbalance between T-helper 1 and T-helper 2 cytokines. Evaluation of cytokines as possible candidate biomarkers for prediction of HCC was performed using soluble Fas(sFas), soluble tumor necrosis factor receptor-II (sTNFR-II), interleukin-2 receptor (IL-2R) and interleukin-8 (IL-8). RESULTS: The following patients were recruited: 79 with HCV infection, 30 with HCC, 32 with chronic liver disease associated with elevated liver enzyme levels (with or without cirrhosis) in addition to 17 with chronic HCV with persistent normal alanine aminotransferase levels (PNALT). Nine normal persons negative either for HCV or for hepatitis B virus were included as a control group. All persons were tested for sFas, sTNFR-II, IL-2R and IL-8 in their serum by quantitative ELISA. HCC patients had higher levels of liver enzymes but lower log-HCV titer when compared to the other groups. HCC patients had also significantly higher levels of sFas, sTNFR-II and IL-2R and significantly lower levels of IL-8 when compared to the other groups. Exclusion of HCC among patients having PNALT could be predicted with 90 % sensitivity and 70.6 % specificity when sTNFR-II is [greater than or equal to] 389 pg/ml or IL-8 is < 290 pg/ml. CONCLUSIONS: Serum TNFR-II, IL-2Ralpha and IL-8, may be used as combined markers in HCV-infected cases for patients at high risk of developing HCC; further studies, however, are mandatory to check these findings before their application at the population level.

Disease progression from chronic hepatitis C to cirrhosis and hepatocellular carcinoma is associated with repression of interferon regulatory factor-1.

BACKGROUND/AIM: Infection with hepatitis C virus (HCV) frequently results in a persistent infection, suggesting that it has evolved efficient mechanism(s) for blocking the host cell's innate antiviral response. The immune response to virus infection results in activation or direct induction of the interferon regulatory factors (IRFs), which are a family of proteins involved in the regulation of interferon (IFN) and IFN inducible genes. IRF-3 and IRF-7 have been shown to play an essential role in virus-dependent signaling, whereas IRF-1 is critical for proper IFN-dependent gene expression. This study has been performed to show the expression profile of IRF-1, IRF-3, and IRF-7 in Egyptian patients with HCV-related liver diseases and hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study included 90 patients, who were positive for HCV infection by reverse transcription PCR, divided into three groups: group I (Gr I) included 30 patients with chronic hepatitis C, group II (Gr II) included 30 patients with liver cirrhosis in addition to group III (Gr III) of 30 patients with HCC. Reverse transcription PCR analysis was performed to determine the expression profile of IRF-1, IRF-3, and IRF-7 genes extracted from the peripheral blood mononuclear cells of those patients. RESULTS: IRF-1expression was significantly higher (P<0.001) in patients of Gr I (86.6%) compared with those in Gr II (46.7%) and Gr III (36.7%), whereas IRF-3 expression was significantly higher (P<0.005) among patients of Gr II (73.3%) in comparison with that in Gr I (50%) and Gr III (36.7%). In contrast, although expression of IRF-7 was higher in Gr II than in the other groups, there was no statistically significant difference (P > 0.05). CONCLUSION: Alterations in IRFs expression might be considered as markers associated with a higher risk of cirrhosis in patients with chronic HCV infection. Expression of IRF-1 and IRF-3 were more prevalent in patients with chronic HCV and cirrhosis, respectively, in comparison with HCC patients. Thus, IRF-1 could be nominated as one of the tumor suppressor factors and could aid in the early detection of HCC.

Assessment of the Proliferative Marker Ki-67 and p53 Protein Expression in HBV- and HCV-related Hepatocellular Carcinoma Cases in Egypt.

BACKGROUND: Chronic HBV and HCV infections are the major risk factors for the development of HCC through a multistep pathway that involves viral and non-viral dependent pathophysiological steps. Hepatic expression of the nuclear proliferative marker ki-67 and the p53 oncoprotein were found to be associated with poor outcome. So, the present study was done to evaluate the changes in expression of Ki-67 and p53 oncoprotein, and to determine p53 gene mutation in HBV/HCV-related HCC Egyptian patients. METHODS: Eight HBV-and 22 HCV-positive HCC cases have been examined for the presence of p53 mutation by immunohistochemistry (IHC) and single-strand conformation polymorphism (SSCP), followed by direct DNA sequencing. HCV were genotyped by LiPA-II. RESULTS: Our results have shown that the proliferative marker ki-67 LI and p53 were highly expressed and significantly related to tumor grade in the Egyptian HCC cases (p<0.05). Also, p53 mutation was found in 16 HCC cases by IHC and in 14 HCC cases by SSCP, only 11 patients showed p53 mutation by sequencing. The highest mutation rate was scored for exon 7 (7 mutations) at codon 249; 4 out of 8 (50%) of HBV-related HCC cases and 3 out of 22 (13.6%) of HCV-related HCC cases, followed by exon 5 (3 mutations) at codons 133, 146, 176 in HCV-related HCC cases, then exon 8 at codon 275 in HCV-related HCC cases. The concordance between the IHC and sequencing analysis was 69%. CONCLUSION: The present study demonstrates the association between the proliferative marker ki-67 and p53 expression with the tumor grade of Egyptian HBV/HCV-related HCC cases. Our results also support the hypothesis that p53 mutations are rather a late event in the carcinogenesis. Also, they suggest that the final steps of hepatocarcinogenesis are common and independent of the aetiology of the viral infection.

Evaluation of simian virus-40 as a biological prognostic factor in Egyptian patients with malignant pleural mesothelioma.

The association between simian virus (SV40) and malignant pleural mesothelioma (MPM) suggests an etiological role for SV40. However, exact pathogenetic mechanisms and possible prognostic value are not clear. The purpose of the present paper was to investigate 40 Egyptian MPM patients for the presence of SV40 DNA, altered Rb expression and p53 gene status using immunohistochemistry and molecular techniques. The relation between SV40, asbestos exposure, Rb, p53 and their contribution to the overall survival (OS) were also assessed. SV40 DNA was detected in 20/40 patients and asbestos exposure in 31 patients; 18 of them were SV40 positive. Altered p53 and Rb expression were detected in 57.5% and 52.5%, respectively, with no p53 mutation. Univariate analysis showed a significant correlation between OS and stage (P = 0.03), performance status (P = 0.04), p53 overexpression (P = 0.05), asbestos exposure (P = 0.002) and SV40 (P = 0.001). Multivariate analysis showed that when SV40 and asbestos exposure were considered together, only combined positivity of both was an independent prognostic factor affecting the OS (P = 0.001). SV40 and asbestos exposure are common in Egyptian MPM, denoting a possible etiological role and a synergistic effect for both agents. Combined positivity for SV40 and asbestos exposure is an independent prognostic factor in MPM, having a detrimental effect on OS.

Presence of simian virus 40 DNA sequences in egyptian patients with lymphoproliferative disorders.

BACKGROUND: Although no definite risk factors have emerged for the different hematological malignancies, a viral cause has been postulated. Several studies have detected SV40 DNA sequences in tumor tissues obtained from non-Hodgkin's lymphoma patients. A link between SV40 and NHL is biologically plausible because SV40 causes hematological malignancies in laboratory rodents. METHODS: We investigated 266 Egyptian cases of different hematological malignancies, for the presence of SV40 DNA using multiplex nested PCR technique. These cases consisted of 158 non-Hodgkin's lymphoma (NHL), 54 Hodgkin's disease(HD), 26 acute lymphocytic leukemia (ALL), 13 acute myeloid leukemia (AML), 8 chronic lymphoblastic leukemia (CLL), 7 chronic myeloid leukemia (CML), in addition to 34 subjects of control group. RESULTS: Our results have shown that SV40 DNA sequences were found in 53.8% of non-Hodgkin lymphoma patients, 29.6% of Hodgkin's disease patients, and 40.7% of different types of leukemia cases. Frequency of SV40 DNA sequences was higher in NHL patients compared to the other tumor cases. Also, frequency of SV40 DNA sequences was significantly higher (p<0.05) in NHL patients than in the control group. Regarding the different histological types of non-Hodgkin's lymphoma, SV40 DNA sequences were detected frequently in diffuse large B-cell lymphoma and in follicular lymphoma. CONCLUSIONS: The present study suggests that SV40 DNA virus is significantly associated with non-Hodgkin's lymphoma and might have a role in the development of these hematological malignancies. Polyomavirus SV40 may act as a cofactor in the pathogenesis of these tumors and this could lead to new diagnostic, therapeutic, and preventive approaches.

Risk factors for cytomegalovirus, hepatitis B and C virus reactivation after bone marrow transplantation.

To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk factors that may be associated with an increased post-BMT death. Among those factors, the importance of pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have determined the effect of prior donor and recipient cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) exposure on the incidence of those viral infections after bone marrow transplantation (BMT). The study included 63 patients presented to the BMT unit; 28 of them underwent transplantation and 35 were not transplanted. All serum markers of CMV, HBV, and HCV infections were monitored using ELISA technique, as well as PCR-DNA for CMV, HBV and HCV RT-PCR techniques for HCV. The incidence of active CMV and HCV was 11/28 (39%) and 6/28 (21%) in post-BMT recipients compared to 2/35 (6%) and 2/35 (6%) in the 35 untransplanted patients (P=0.00003 and P=0.05). Whereas active HBV infection was non significantly (P=0.13) higher 3/28 (11%) in the BMT patients in comparison to 1/35 (3%) in untransplanted patients. Ten out of the 19 (53%) of the CMV-seropositive recipients developed CMV reactivation compared to 1/9 (11%) of the CMV-seronegative recipients who developed CMV seroconversion. In addition, 3/8 (38%) of the HBV-seropositive recipients developed HBV reactivation in comparison to 0/20 of the HBV-seronegative recipients. Moreover, 5/13 (39%) of the HCV-seropositive recipients developed HCV reactivation in comparison to 1/16 (6%) of the HCV-seronegative recipients who developed HCV seroconversion. In conclusion, previous exposure to CMV, HBV, and HCV infections in the recipients of BMT patients were found to influence the risk of developing those viral infections.