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1.
Sci Rep ; 14(1): 13015, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844752

RESUMO

Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles are prevalent in many industries, including food and medicine, but their small size raises concerns about potential cellular damage and genotoxic effects. However, there are very limited studies available on their genotoxic effects. Hence, this was done to investigate the effects of multiple administration of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs on genomic DNA stability, mitochondrial membrane potential integrity and inflammation induction in mouse brain tissues. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs at a dose level of 50 mg/kg b.w three times a week for 2 weeks. Genomic DNA integrity was studied using Comet assay and the level of reactive oxygen species (ROS) within brain cells was analyzed using 2,7 dichlorofluorescein diacetate dye. The expression level of Presenilin-1, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) genes and the integrity of the mitochondrial membrane potential were also detected. Oral administration of Ca(OH)2NPs caused the highest damage to genomic DNA and mitochondrial membrane potential, less genomic DNA and mitochondrial damage was induced by CaTiO3NPs administration while administration of Y2O3NPs did not cause any remarkable change in the integrity of genomic DNA and mitochondrial membrane potential. Highest ROS generation and upregulation of presenilin-1, TNF-α and IL-6 genes were also observed within the brain cells of mice administrated Ca(OH)2NPs but Y2O3NPs administration almost caused no changes in ROS generation and genes expression compared to the negative control. Administration of CaTiO3NPs alone slightly increased ROS generation and the expression level of TNF-α and IL-6 genes. Moreover, no remarkable changes in the integrity of genomic DNA and mitochondrial DNA potential, ROS level and the expression level of presenilin-1, TNF-α and IL-6 genes were noticed after simultaneous coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs. Coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs mitigated Ca(OH)2NPs and CaTiO3NPs induced ROS generation, genomic DNA damage and inflammation along with restoring the integrity of mitochondrial membrane potential through Y2O3NPs scavenging free radicals ability. Therefore, further studies are recommended to study the possibility of using Y2O3NPs to alleviate Ca(OH)2NPs and CaTiO3NPs induced genotoxic effects.


Assuntos
Hidróxido de Cálcio , Dano ao DNA , Inflamação , Potencial da Membrana Mitocondrial , Nanopartículas , Espécies Reativas de Oxigênio , Titânio , Ítrio , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Dano ao DNA/efeitos dos fármacos , Hidróxido de Cálcio/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Titânio/química , Titânio/toxicidade , Inflamação/metabolismo , Inflamação/patologia , Ítrio/química , Nanopartículas/química , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Masculino , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , DNA Mitocondrial/metabolismo
2.
Sci Rep ; 14(1): 10964, 2024 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-38744871

RESUMO

Due to vincristine sulfate's (VCR sulfate) toxicity and non-specific targeting, which might adversely damage healthy cells, its clinical application is restricted. In this study, we loaded VCR sulfate on exosomes generated from mesenchymal stem cells (MSCs) to enhance its targeted distribution. Exosomes are able to deliver molecules to specific cells and tissues and have therapeutic potential. In this study, we isolated exosomes from MSCs, and using probe-sonication approach loaded them with VCR sulfate. Using SRB assay, the cytotoxicity of VCR sulfate-Exo was assessed in T47D breast cancer cells, and the results were contrasted with those of free VCR sulfate. Then We labeled markers (CD44+/CD24-) in the cell line to assess the targeting effectiveness of VCR sulfate-Exo using flow cytometry. Our results showed that the cytotoxicity of VCR sulfate-Exo was nearly the same as that of VCR sulfate. Flow cytometry analysis revealed that VRC sulfate-Exo was more effectively targeted to MSCs than free VCR sulfate. Our study shows that loading VCR sulfate to MSCs-derived exosomes can improve their targeted delivery and lessen their side effects. Additional research is required to determine VCR sulfate-Exo's in vivo effectiveness and safety and improve the loading and delivery strategies.


Assuntos
Neoplasias da Mama , Exossomos , Células-Tronco Mesenquimais , Células-Tronco Neoplásicas , Vincristina , Exossomos/metabolismo , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Linhagem Celular Tumoral , Vincristina/farmacologia , Portadores de Fármacos/química
3.
Egypt Heart J ; 76(1): 30, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441828

RESUMO

BACKGROUND: Chronic total occlusion (CTO) lesions in coronary arteries pose a significant challenge for coronary interventionists, often leading to referrals for coronary artery bypass graft surgery (CABG). Successful percutaneous coronary intervention (PCI) for CTOs requires accurate assessment of procedural potential. This study, comprising 100 Egyptian patients aged 37-81, compares the predictive efficacy of various CTO scoring systems in PCI success determination. Patients with CTO in at least one coronary artery, planned for elective PCI based on objective evidence of ischemia, were included. Experienced operators performed PCI, recording procedural variables, and assessing complications. Logistic regression analysis revealed an inverse linear relationship between success rates and score values across all systems. RESULTS: Although, the predictive capacity of the scores was similar, with slight differences. The Euro CTO (CASTLE) score10 exhibited superior predictive efficacy, followed by the CL score9, while PROGRESS8 and J-CTO7 scores showed lower significance. ORA CTO11 score demonstrated intermediate predictive ability, and PROGRESS score8 had the least predictive value. CONCLUSION: The CASTLE score10 proved most effective in predicting PCI success for CTO cases in Egyptian patients, with operators advised to choose scoring systems based on experience and case characteristics. Proper planning remains crucial for optimizing success rates in CTO PCI procedures, irrespective of the scoring system employed.

4.
BMC Surg ; 24(1): 7, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172802

RESUMO

BACKGROUND: To evaluate the impact of tumor size on the perioperative and long-term outcomes of liver resection for hepatocellular carcinoma (HCC). METHODS: We reviewed the patients' data who underwent liver resection for HCC between November 2009 and 2019. Patients were divided into 3 groups according to the tumor size. Group I: HCC < 5 cm, Group II: HCC between 5 to 10 cm, and Group III: HCC ≥ 10 cm in size. RESULTS: Three hundred fifteen patients were included in the current study. Lower platelets count was noted Groups I and II. Higher serum alpha-feto protein was noted in Group III. Higher incidence of multiple tumors, macroscopic portal vein invasion, nearby organ invasion and presence of porta-hepatis lymph nodes were found in Group III. More major liver resections were performed in Group III. Longer operation time, more blood loss and more transfusion requirements were found in Group III. Longer hospital stay and more postoperative morbidities were noted in Group III, especially posthepatectomy liver failure, and respiratory complications. The median follow-up duration was 17 months (7-110 months). Mortality occurred in 100 patients (31.7%) and recurrence occurred in 147 patients (46.7%). There were no significant differences between the groups regarding recurrence free survival (Log Rank, p = 0.089) but not for overall survival (Log Rank, p = 0.001). CONCLUSION: HCC size is not a contraindication for liver resection. With proper selection, safe techniques and standardized care, adequate outcomes could be achieved.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Estudos Retrospectivos , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatectomia/métodos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia
5.
Sci Rep ; 13(1): 19633, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949924

RESUMO

Intensive uses of Calcium hydroxide (Ca(OH)2NPs), calcium titanate (CaTiO3NPs) and yttrium oxide (Y2O3NPs) nanoparticles increase their environmental release and human exposure separately or together through contaminated air, water and food. However, too limited data are available on their genotoxicity. Therefore, this study explored the effect of Ca(OH)2NPs, CaTiO3NPs or/and Y2O3NPs administration on the genotoxicityand oxidative stress induction in mice hepatic tissue. Mice were orally administered Ca(OH)2NPs, CaTiO3NPs and Y2O3NPs separately or simultaneously together at a dose level of 50 mg/kg b.w. for two successive weeks (3 days per week). Marked induction of DNA damage noticed after oral administration of Ca(OH)2NPs or CaTiO3NPs alone together with high Ca(OH)2NPs induced reactive oxygen species (ROS) generation and a slight CaTiO3NPs induced ROS production were highly decreased after simultaneous coadministration of administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs up to the negative control level. Oral administration of Y2O3NPs alone also did not cause observable changes in the genomic DNA integrity and the ROS generation level compared to the negative control levels. Similarly, significant elevations in P53 gene expression and high reductions in Kras and HSP-70 genes expression were observed only after administration of Ca(OH)2NPs alone, while, remarkable increases in the Kras and HSP-70 genes expression and non-significant changes in p53 gene expression were noticed after administration of CaTiO3NPs and Y2O3NPs separately or simultaneously together with Ca(OH)2NPs. Conclusion: Ca(OH)2NPs exhibited the highest genotoxic effect through oxidative stress induction and disruption of apoptotic (p53 and Kras) and protective (HSP-70) genes expression. Slight DNA damage was noticed after CaTiO3NPs administration. However, administration of Y2O3NPs alone was non-genotoxic and coadministration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs restored genomic DNA integrity and normal expression of apoptotic p53 and protective HSP-70 genes disrupted by Ca(OH)2NPs and CaTiO3NPs. Thus co-administration of Y2O3NPs with Ca(OH)2NPs and CaTiO3NPs is recommended to counter Ca(OH)2NPs and CaTiO3NPs induced genotoxicity and oxidative stress.


Assuntos
Cálcio , Nanopartículas , Camundongos , Humanos , Animais , Cálcio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Hidróxido de Cálcio/toxicidade , Proteínas Proto-Oncogênicas p21(ras)/genética , Estresse Oxidativo , Proteína Supressora de Tumor p53/metabolismo , Nanopartículas/toxicidade , Dano ao DNA , DNA/metabolismo
6.
J Gastrointest Surg ; 26(10): 2070-2081, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36002785

RESUMO

BACKGROUND: Bile leakage (BL) is one of the commonest morbidities after hepatic resection for hepatocellular carcinoma (HCC). The current study was conducted to evaluate the incidence and different predictive factors for BL after hepatic resection for HCC, and to evaluate of the impact of BL on the long-term survival outcomes. METHODS: We reviewed the patients' data who underwent hepatic resection for HCC during the period between June 2010 and June 2019. RESULTS: A total of 293 patients were included in the study. BL occurred in 17 patients (5.8%). More Child-Pugh class B patients were found in BL group. There were no significant differences between the two groups except for tumor site, macroscopic portal vein invasion, extent of liver resection, Pringle maneuver use, intraoperative blood loss, and transfusions. Longer hospital stay, higher grades of post-hepatectomy liver failure, and abdominal collections were noted in BL group. After median follow-up duration of 17 months (4-110 months), there were no significant differences between BL and non-BL group regarding overall survival (log-rank, p = 0.746) and disease-free survival (log-rank, p = 0.348). In multivariate analysis, Child-Pugh class, macroscopic portal vein invasion, liver resection extent (minor/major), and Pringle's maneuver use were the only significant predictors of BL. CONCLUSION: BL did not significantly impair the long-term outcomes after hepatic resection for HCC. Child-Pugh class, macroscopic portal vein invasion, liver resection extent (minor/major), and Pringle's maneuver use were the main risk factors of BL in the current study.


Assuntos
Doenças Biliares , Carcinoma Hepatocelular , Neoplasias Hepáticas , Bile , Doenças Biliares/cirurgia , Carcinoma Hepatocelular/patologia , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Estudos Retrospectivos
7.
Bioorg Chem ; 128: 106099, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35994884

RESUMO

The present study involves design and synthesis of five series of 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines 9a-l, 11a-e, 13a-c, 14a-f and 15a-e. Candidates 9a-l and 11a-e were evaluated for their EGFR and HER2 inhibitory activity compared to Lapatinib. Compounds 9b, 9d, 9f, 11b and 11c were further screened for their in vitro cytotoxicity against two human breast cancer cell lines: AU-565 and MDA-MB-231 in addition to normal breast cell line MCF10A. Compound 9d revealed a remarkable cytotoxic efficacy against AU-565 cell line (IC50 = 1.54 µM) relative to Lapatinib (IC50 = 0.48 µM), whereas compounds 9d and 11c showed a superior cytotoxicity towards MDA-MB-231 (IC50 = 2.67 and 1.75 µM, respectively) in comparison to Lapatinib (IC50 = 9.29 µM). Moreover, compounds 13a-c, 13a-c, 14a-f and 15a-e were tested for their VEGFR-2 inhibitory activity compared to Sorafenib. Compounds 13a, 14c and 14e exhibited remarkable inhibition (IC50 = 79.80, 50.22 and 78.02 nM, respectively) relative to Sorafenib (IC50 = 51.87 nM). In vitro cytotoxicity of these compounds against HepG2, HCT-116 and normal cell (WISH) revealed a superior cytotoxicity against HepG2, HCT-116 especially 13a (IC50 = 17.51 and 5.56 µM, respectively) and 14c (IC50 = 10.40 and 3.37 µM, respectively) compared to Sorafenib (IC50 = 19.33 and 6.82 µM, respectively). Compounds 9d, 11c and 14c were subjected to cell cycle analysis and apoptotic assay. Molecular docking and ADME prediction studies were fulfilled to illustrate the interaction of the potent derivatives with the hot spots of the active site of EGFR, HER2 and VEGFR-2 along with prediction of their pharmacokinetic and physicochemical properties.


Assuntos
Antineoplásicos , Quinazolinas , Antineoplásicos/química , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB , Humanos , Lapatinib/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases , Quinazolinas/química , Quinazolinas/farmacologia , Sorafenibe/farmacologia , Relação Estrutura-Atividade , Receptor 2 de Fatores de Crescimento do Endotélio Vascular
8.
Clin Neurol Neurosurg ; 220: 107374, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35961255

RESUMO

BACKGROUND: Vaccination against the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) virus is recommended in multiple sclerosis (MS) to reduce the risk of complications from Coronavirus disease 2019 (COVID-19) infection. These vaccines were not investigated in people with MS (PWMS). OBJECTIVE: This study aimed to report the short-term safety of the COVID-19 vaccines among PWMS. METHODS: Pfizer-BioNTech mRNA (BNT162b2) vaccine and Oxford-Astra Zenecaa chimpanzee adenovirus-vectored (ChAdOx1 nCoV-19) vaccine have been approved to be used in Kuwait since December 2021. PWMS registered in Kuwait national registry were contacted by phone, WhatsApp, or through face-to-face interviews and were invited to complete our questionnaire. Demographic, clinical data, symptoms following the vaccine, worsening of pre-existing MS symptoms, and occurrence of relapse were recorded. RESULTS: Of the 820 PWMS, 647 completed the questionnaire. Between January 2021 and 31 August 2021, 383 (59.28%) PWMS received at least one dose of the approved vaccinations versus 63.4% of the general population on the same date. Their mean age was 36.82 + 8.80, and most of them, 247 (64.3%), were females. A total of 356 vaccinated cohorts (92.6%) were treated with disease-modifying therapies. Adverse events were reported by 261 (68.15%) subjects. One case of COVID-19 infection was encountered after the first dose of the BNT162b2 vaccine. Twenty-one (5.48%) cases reported worsening of pre-existing MS symptoms after the vaccine. Five patients (1.31%) reported relapse after the COVID-19 vaccine. The most common adverse events of the COVID-19 vaccine were pain at the injection site, fatigue, low-grade fever, and body ache; and resolved within one week. There was no significant association between use of disease modifying therapy (DMT) and COVID-19 vaccine adverse events. CONCLUSION: BNT162b2 and ChAdOx1 nCoV-19 are safe for PWMS. No increased risk of relapse activity or worsening of pre-existing MS symptoms.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Esclerose Múltipla , Vacinas , Adulto , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , SARS-CoV-2 , Vacinação
9.
J Invest Surg ; 35(8): 1621-1625, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35694760

RESUMO

Background: Cardiac surgeries induce many inflammatory responses with remarkable clinical implications. Tryptophan (Trp) is a precursor for serotonin, melatonin and kynurenine (Kyn). Plasma kynurenic acid (Kyna) and Kyn concentrations are thought to be related to the severity of inflammation. Plasma Trp/Kyn ratio is used to measure inflammatory cytokine activity.Methods: We performed the current longitudinal study in a tertiary care center and included 62 patients divided into two groups; group A (on-pump CABG patients) and group B (off-pump CABG patients). Plasma Trp and Kyn were measured using the high-performance liquid chromatography (HPLC) technique. Serum interlukin-6 (IL-6) and white blood cells (WBCs) were measured using ELISA and routine blood count, respectively.Results: The present study revealed that the intraoperative levels of plasma Kyn, IL-6 and WBCs were significantly increased while the plasma Trp/Kyn ratio was significantly decreased in both the groups; however, the changes were more significant in the on-pump CABG group. Moreover, the levels in both the groups returned to preoperative levels 72 h postoperative. Our study has shown that WBCs is positively correlated with IL-6, but has negative correlation with Trp/Kyn ratio.Conclusions: Kyn and Trp/Kyn ratio might be utilized as markers of the severity of inflammation in major surgery. In addition, off-pump CABG might be more preferable than on-pump CABG regarding stress and release of inflammatory markers.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Cinurenina , Biomarcadores , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Humanos , Inflamação/etiologia , Interleucina-6 , Cinurenina/metabolismo , Estudos Longitudinais , Síndrome de Resposta Inflamatória Sistêmica , Triptofano/metabolismo
10.
J Clin Neurosci ; 99: 311-316, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35339046

RESUMO

A cross-sectional hospital records-based study was conducted to evaluate the prevalence, severity, outcomes, and identify demographic and clinical risk factors of coronavirus disease (COVID-19) in patients with MS. The study was conducted at multiple clinics in Oman, Kuwait, and the United Arab Emirates (UAE) from March 2020 to February 2021. The association of patient demographics, MS disease characteristics, and use of disease-modifying therapies with outcomes of COVID-19 illness were evaluated using odds ratio. A total of 134 MS patients with COVID-19 (prevalence rate of 3.7%) having a median age of 35.5 years were analyzed in the study. A majority (126 [94.0%]) of patients had mild COVID-19 illness and 122 (91.0%) made a full recovery, while 1 (0.7%) patient died. The median EDSS score reported in the study was low (1.0). Univariate regression analysis showed high EDSS scores, progressive MS disease, and use of anti-CD20 therapy such as rituximab as risk factors for moderate to severe COVID-19 requiring hospitalization. Comorbidities were associated with a higher risk of non-recovery from COVID-19 in both univariate and multivariate analyses. Age, sex, smoking history, and duration of MS did not show a significant association with severity or adverse COVID-19 disease outcome. Identification of risk factors can aid in improving the treatment and monitoring of pwMS and COVID-19.


Assuntos
COVID-19 , Esclerose Múltipla , Adulto , COVID-19/epidemiologia , Estudos Transversais , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/terapia , Prevalência , Fatores de Risco , SARS-CoV-2
11.
J Surg Res ; 266: 269-283, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34038849

RESUMO

BACKGROUND: To evaluate our experience of liver resection for hepatocellular carcinoma (HCC) patients associated with macroscopic portal vein invasion (PVI). METHODS: Consecutive HCC patients who underwent liver resection for HCC between November 2009 & June 2019 were included. To overcome selection bias between patients with and without macroscopic PVI, we performed 1:1 match using propensity score matching (PSM). RESULTS: Macroscopic PVI was detected in 37 patients (12.8%). We divided our patients into two groups according to the presence of macroscopic PVI. After PSM, 36 patients of PVI group were matched with 36 patients from Non-PVI group. After PSM, both groups were well balanced regarding tumor site, number, liver resection extent and type. Longer operation time and more blood loss were noted in PVI group. Higher incidence of post-operative morbidities occurred in PVI group especially, post-hepatectomy liver dysfunction. The 1-, 2-, and 3-y overall survival rates for Non-PVI group were 85.3%, 64.6%, and 64.6% & 69.8%, 42%, and 0% for PVI group, respectively (P = 0.009). There were no significant differences regarding the recurrence rate, site, and its management. The 1-, 2-, and 3-y disease-free survival (DFS) rates for Non-PVI group were 81.7%, 72.3%, and 21.7% & 67.7%, 42.3%, and 0% for PVI group, respectively (P = 0.172). CONCLUSION: Surgical management of advanced HCCs with macroscopic PVI is feasible, and associated with comparable DFS but poorer overall survival, compared to patients without PVI.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Egito/epidemiologia , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Adulto Jovem
12.
Langenbecks Arch Surg ; 406(1): 87-98, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32778915

RESUMO

PURPOSE: Post-hepatectomy liver failure (PHLF) is one of the most feared morbidities after liver resection (LR) for hepatocellular carcinoma (HCC). We aimed to investigate the incidence and predictors of PHLF after LR for HCC and its impact on survival outcomes. METHODS: We reviewed the patients who underwent LR for HCC during the period between January 2010 and 2019. RESULTS: Two hundred sixty-eight patients were included. Patients were divided into two groups according to the occurrence of PHLF, defined according to ISGLS. The non-PHLF group included 138 patients (51.5%), while the PHLF group included 130 patients (48.5%). Two hundred forty-six patients (91.8%) had hepatitis C virus. Major liver resections were more performed in the PHLF group (40 patients (30.8%) vs. 18 patients (13%), p = 0.001). Longer operation time (3 vs. 2.5 h, p = 0.001), more blood loss (1000 vs. 500 cc, p = 0.001), and transfusions (81 patients (62.3%) vs. 52 patients (37.7%), p = 0.001) occurred in PHLF group. The 1-, 3-, and 5-year Kaplan-Meier overall survival rates for the non-PHLF group were 93.9%, 79.5%, and 53.9% and 73.2%, 58.7%, and 52.4% for the PHLF group, respectively (log rank, p = 0.003). The 1-, 3-, and 5-year Kaplan-Meier disease-free survival rates for the non-PHLF group were 77.7%, 42.5%, and 29.4%, and 73.3%, 42.9%, and 25.3% for the PHLF group, respectively (log rank, p = 0.925). Preoperative albumin, bilirubin, INR, and liver cirrhosis were significant predictors of PHLF in the logistic regression analysis. CONCLUSION: Egyptian patients with HCC experienced higher PHLF incidence after LR for HCC. PHLF significantly affected the long-term survival of those patients.


Assuntos
Carcinoma Hepatocelular , Falência Hepática , Neoplasias Hepáticas , Carcinoma Hepatocelular/cirurgia , Hepatectomia/efeitos adversos , Humanos , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos
13.
Urol Ann ; 12(3): 229-235, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33100747

RESUMO

AIMS: Robot-assisted laparoscopic intracorporeal urinary diversion (ICUD) has several potential benefits of a smaller incision and reduced pain over extracorporeal urinary diversion (ECUD). We compared the perioperative outcomes of patients who have undergone these procedures with or without cystectomy. SUBJECTS AND METHODS: This study is a retrospective chart review of patients who underwent ICUD and ECUD in a single tertiary referral hospital. Patient demographics, perioperative outcomes, and the 90-day postoperative complications were collected. STATISTICAL ANALYSIS USED: The statistical analyses were performed using the Chi-square test for categorical variables which are specified as frequency (percentage). RESULTS: Thirty-five patients who underwent urinary diversion procedure were identified for inclusion in the study. Of these patients, 14 underwent ICUD and 21 underwent ECUD. The mean operative time was longer in the ICUD group compared to that of the ECUD (457.14 ± 103.91 and 388.29 ± 110.17, respectively, P = 0.07). The median blood loss was statistically significantly lower in the ICUD group (250 ml) than in the ECUD group (450 ml, P = 0.05). The mean hospital stay was marginally longer for the ECUD group (8.1 days) as compared to the ICUD group (6.3 days, P = 0.17). There was no difference in the readmission or reoperation rates after 30 days. The 90-day complication rate was not statistically significantly different between the two groups, but a trend favoring ICUD (64%) over ECUD (71%, P = 0.656) was noted. CONCLUSIONS: Robot-assisted ICUD is associated with decreased blood loss, and there is a trend toward fewer postoperative complications and shorter hospital stays.

14.
Bioorg Chem ; 98: 103726, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32171987

RESUMO

The present study describes the synthesis of 6-bromo-2-(pyridin-3-yl)-4-substituted quinazolines starting from 4-chloro derivative VI via the reaction with either phenolic compounds to obtain VIIa-f, IXa-d, 2-amino-6-(un)substituted benzothiazole to produce VIIIa-c or hydrazine hydrate to give X. Reaction of the hydrazino functionality of X with appropriate acid anhydride, acid chloride or aldehyde affords XIa-c, XIIa-c and XIVa-i, respectively. The target compounds were screened for their efficacy as EGFR inhibitors compared to gefitinib. Compounds eliciting superior EGFR inhibitory activity were further screened for their in vitro cytotoxicity against two human cancer cell lines namely: MCF7 (breast) and A549 (lung), in addition to normal fibroblast cell WI38 relative to gefitinib as a reference. Furthermore, compounds that showed potent inhibitory activity on wild-type EGFR were screened against mutant EGFR and assayed for their cytotoxicity against mutant EGFR-expressing cell lines PC9 and HCC827. The unsubstituted benzothiazol-2-amine VIIa showing superior EGFR inhibition (IC50 = 0.096 µM) and anticancer activity against MCF-7 cell line (IC50 = 2.49 µM) was subjected to cell cycle analysis and apoptotic assay. Moreover, a molecular docking study was performed to investigate the interaction of some representive compounds with the active site of EGFR- TK.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Quinazolinas/síntese química , Quinazolinas/química , Relação Estrutura-Atividade , Células Tumorais Cultivadas
15.
Turk J Urol ; 45(6): 437-443, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31603418

RESUMO

OBJECTIVE: To evaluate the morbidity of the magnitip double-J stent (DJ), compare its morbidity to the standard stent, and evaluate the possibility of retrieving the magnetic tip of the DJ stent without cystoscopy. MATERIAL AND METHODS: A total of 50 patients having a lower ureteric stone, who underwent uretroscopic stone retrieval and required the use of a DJ, were randomly assigned to 2 groups, each containing 25 patients. Patients in group A were subjected to exploration with a uretroscope and a magnitip DJ while those in group B received a uretroscope and a standard DJ. The morbidity of both types of DJs was assessed by the Arabic version of the ureteral stent symptom questionnaire (USSQ). RESULTS: There was a high level of statistically significant differences between the two groups with regards to the total score of the USSQ, which were higher in group A as compared to group B (126.96±14.76 vs. 98.24±12.9) (p=0.001). Further, the cost of the total procedure was significantly higher in group B (9600±1456.59 vs. 8444±783.73) (p=0.001). No statistically significant difference was found between both groups regarding the application, retrieval accuracy, and discomfort caused by DJ removal. CONCLUSION: The morbidity caused by the magnetic DJ was found to be higher. However, the removal of the magnetic DJ was less costly than the standard DJ.

16.
Arab J Urol ; 17(1): 30-39, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33110660

RESUMO

Objective: To evaluate the safety and effectiveness of laparoscopic sacrocolpopexy (LSC)/laparoscopic sacrohysteropexy (LSH) at 1-year follow-up for female pelvic-organ prolapse (POP). Patients and methods: In all, 52 patients were included and underwent LSC/LSH in the Eldemerdash Hospital, Ain Shams University, Cairo, Egypt. All patients with POP, with Grade ≥II of any anatomical site (anterior, posterior or combined) who were medically fit for general anaesthesia, were included in the study. Patients with previous major abdominal surgery, a body mass index (BMI) of >40 kg/m2 or un-correctable bleeding diatheses, were excluded. Preoperative data, peri- and postoperative functional and anatomical outcomes were assessed. The patients were followed-up at 3, 6 and 12 months postoperatively. Results: Pre- and postoperative data were available for the 52 patients operated on for POP. The subjective cure rate was 92.3% and the objective cure rate was 98.1%. Failure was defined as recurrence of Grade ≥II POP. Conclusion: LSC/LSH is a safe and effective procedure for the treatment of female POP due to its durable results and low rates of complications with high objective and subjective cure rates. Abbreviations: BMI: body mass index; (RA)LSC: (robot-assisted) laparoscopic sacrocolpopexy; LSH: laparoscopic sacrohysteropexy; PFDI-20: Pelvic Floor Distress Inventory; PFIQ-7: Pelvic Floor Impact Questionnaire; POP: pelvic-organ prolapse; QoL: quality of life; SUI: stress urinary incontinence; TVM: total transvaginal mesh; VVP: vaginal vault prolapse.

17.
Int J Surg Case Rep ; 54: 23-27, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30513494

RESUMO

INTRODUCTION: The adrenal gland is a rare site for hepatocellular carcinoma (HCC) recurrence after living-donor liver transplantation (LDLT). Solitary adrenal recurrence can be managed by surgical excision, with expected better survival outcomes. We describe a rare case of successful left adrenalectomy of solitary recurrent HCC in the left adrenal gland 5 years after LDLT. PRESENTATION: 59 years male patient with HCC complicating chronic HCV infection received a right hemi-liver graft from his son. The actual graft weight was 1208 g and GRWR was 1.5. The patient started oral direct acting antiviral drugs for recurrent HCV 2 years after LDLT. A left adrenal mass was detected on follow up radiology. No other metastatic lesions were detected on metastatic workup. Left adrenalectomy was done by an anterior approach. The postoperative course was uneventful and was discharged a week after operation. Postoperative pathological and immune-histochemical examinations confirmed the metastatic HCC nature of the mass. The patient is under regular follow up with no recurrences 6 month after resection. DISCUSSION: There is no consensus regarding the management of HCC recurrence after LDLT. Most patients had multi-organ recurrences and usually offered palliative or supportive care. Solitary HCC recurrence offers a better chance for more aggressive therapy, offering better prognosis. CONCLUSION: Solitary adrenal recurrence of HCC after LDLT is extremely rare. Strict follow up protocol is necessary to allow early detection of tumor recurrence. Curative surgical resection is a safe option associated with low morbidity and expected to have a good long-term survival.

18.
Arab J Urol ; 16(4): 453-459, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30534447

RESUMO

OBJECTIVES: To evaluate the incidence and risk factors for the development of flank incisional hernias or bulges following surgical flank approaches to the kidney. PATIENTS AND METHODS: In all, 100 consecutive adult patients who underwent variable renal surgeries via flank approaches were included in this prospective study. The incidence and risk factors for flank hernias and bulges were studied at 1- and 6-months postoperatively. RESULTS: At 6 months postoperatively, the incidence of flank bulge was 14% and for lumbar hernia was 10%. The univariate analysis showed 13 significant factors to be associated with the occurrence of a flank bulge or hernia following flank incisions. When the significant risk factors in the univariate analysis were studied by multivariate analysis, using a logistic regression analysis, four independent risk factors were identified. These were: body mass index (BMI) ≥26.3 kg/m2 (P = 0.04), the use of a self-retaining retractor during surgery (P = 0.02), not preserving or identifying the neurovascular bundle (NVB) during surgery (P = 0.028), and postoperative abdominal distention (P = 0.001). Moreover, all cases included in our study who underwent en masse wound closure, developed surgical wound infection or who had constipation developed postoperative flank bulge or hernia. CONCLUSION: High BMI, the use of self-retaining retractor, not identifying or preserving the NVB, postoperative abdominal distention, en masse wound closure, surgical wound infection, and constipation are significant risk factors associated with postoperative flank hernia and bulge.

19.
World J Urol ; 36(7): 1139-1147, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29450731

RESUMO

PURPOSE: The extracorporeal shockwave lithotripsy (ESWL) remains the most common first line of treatment for renal stones in the pediatric population. The purpose of this study is to evaluate and compare the outcomes of the ESWL and mini-percutaneous nephrolithotomy (mini-PCNL). PATIENTS AND METHODS: A total of 108 patients younger than 12 years of age with 1-2 cm single renal stone (pelvic or calyceal) were randomized into two groups, each containing 54 patients. Patients in group A were subjected to mini-PCNL using 16.5 Fr percutaneous sheath while those in group B underwent ESWL using Dornier Compact Sigma. RESULTS: The stone-free rate (SFR) after first session was 88.9% (48 cases) and 55.6% (30 cases) for groups A and B, respectively. The difference is highly statistically significant P = 0.006. Two patients (3.7%) in group A needed 2nd session of PCNL, while 18 patients (33.3%)in group B needed a 2nd session, of theses 18 patients six patients needed a 3rd session of ESWL. After the third session of ESWL and second look PCNL the stone-free rates were 92.59% (50 cases) and 88.89% (48 cases) for groups A and B, respectively, (P = 0.639), which is statistically insignificant. The mean hospital stay and fluoroscopy exposure were significantly longer in the mini-PCNL group. The complication rate in groups A and group B were (22.2%) and (14.8%), respectively, which is statistically insignificant (P = 0.484). CONCLUSIONS: According to Clavien grade of complications mini-PCNL is a safe procedure, and after three session of ESWL, mini-PCNL has a similar stone-free rate with a lower retreatment rate. However, the mini-PCNL has more radiation exposure, and requires a longer hospital stay.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Cálculos Renais/terapia , Nefrolitotomia Percutânea/métodos , Criança , Pré-Escolar , Tratamento por Ondas de Choque Extracorpóreas/efeitos adversos , Feminino , Humanos , Masculino , Nefrolitotomia Percutânea/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
20.
Pol J Radiol ; 81: 90-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27026793

RESUMO

BACKGROUND: To assess semiquantitative parameters of dynamic contrast-enhanced perfusion MR imaging (DCE) in differentiation of subtypes of renal cell carcinoma (RCC). MATERIAL/METHODS: Prospective study conducted upon 34 patients (27 M, 7 F, aged 25-72 ys: mean 45 ys) with RCC. Abdominal dynamic contrast-enhanced gradient-recalled echo MR sequence after administration of gadopentetate dimeglumine was obtained. The time signal intensity curve (TIC) of the lesion was created with calculation of enhancement ratio (ER), and washout ratio (WR). RESULTS: The subtypes of RCC were as follows: clear cell carcinomas (n=23), papillary carcinomas (n=6), and chromophobe carcinomas (n=5). The mean ER of clear cell, papillary and chromophobe RCC were 188±49.7, 35±8.9, and 120±41.6 respectively. The mean WR of clear cell, papillary and chromophobe RCCs were 28.6±6.8, 47.6±5.7 and 42.7±10, respectively. There was a significant difference in ER (P=0.001) and WR (P=0.001) between clear cell RCC and other subtypes of RCC. The threshold values of ER and WR used for differentiating clear cell RCC from other subtypes of RCC were 142 and 38 with areas under the curve of 0.937 and 0.895, respectively. CONCLUSIONS: We concluded that ER and WR are semiquantitative perfusion parameters useful in differentiation of clear cell RCC from chromophobe and papillary RCCs.

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