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Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already diagnosed and operated patient of Ulcerative colitis.
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ABSTRACT Colorectal carcinoma (CRC) is the third most commonly diagnosed cancer worldwide and is the second most common cause of cancer-related deaths. However, the Omani population shares the major burden as the most prevalent carcinoma. The disease is comparatively higher in males than females. Patients with pre-existing risk factors, including inflammatory bowel disease, are at increased risk of developing neoplasia. Among the various histopathological subtypes of adenocarcinoma in the rectum, signet ring cell carcinoma is the rarest and accounts for approximately 1% of the cases. Given the aggressive nature of this tumor, advanced presentation, stage, and poor prognosis, regular endoscopic surveillance is essential. Hereby, we report a rare case of signet ring cell carcinoma arising in the rectal stump in an already diagnosed and operated patient of Ulcerative colitis.
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OBJECTIVES: Totally implantable central venous access ports (port-a-caths) are increasingly used for the safe administration of chemotherapy; however, their use is associated with complications. This study reviews patterns of complications, reasons for premature removal and the duration of the use of port-a-caths in patients receiving cancer treatment at Sultan Qaboos University Hospital (SQUH) and compares the infection rate with the literature and the researchers' experiences. METHODS: This retrospective follow-up study included patients who had received cancer treatment through a port-a-cath and were admitted to SQUH between January 2007 and April 2019. Demographic features, underlying diagnosis, clinical stage, treatment, duration of use and the cause of premature removal of the port-a-cath were recorded. RESULTS: A total of 516 port-a-caths were inserted in 482 cancer patients. The majority of devices were implanted by interventional radiologists (n = 459; 89.0%) and the right internal jugular vein was most frequently accessed (n = 396; 76.7%). The mean indwelling time of a port-a-cath was 288 days (range: 3-1,872 days) for patients with complications and 550 days (range: 7-3,123 days) for patients without complications. Port-a-cath-related infection was the main complication (n = 63; 12.2%). Patient age, gender, treatment intent, underlying diagnosis, clinical stage, chemotherapy regimen, number of treatment courses, operator implanting the port, the type of micro-organism isolated from the port-a-cath and body mass index were significant factors affecting catheter indwelling time (P <0.05). On multivariate analysis, however, none of the factors was found to be significant. CONCLUSION: Infection was the most common complication necessitating port-a-cath removal. The infection rate was much lower than the researchers' previous experience and compares favorably with several published reports.
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Antineoplásicos/administração & dosagem , Infecções Relacionadas a Cateter/etiologia , Cateterismo Venoso Central/efeitos adversos , Veias Jugulares/cirurgia , Neoplasias/tratamento farmacológico , Sepse/etiologia , Dispositivos de Acesso Vascular/efeitos adversos , Antineoplásicos/uso terapêutico , Feminino , Seguimentos , Hospitais Universitários , Humanos , Masculino , Omã , Infecções Relacionadas à Prótese/etiologia , Estudos Retrospectivos , Dispositivos de Acesso Vascular/microbiologiaRESUMO
PURPOSE: Evidence from industrialized/developed countries showed that colorectal cancer (CRC) incidence rates have significantly dropped due to the widespread use of colonoscopy. In Arab countries, however, the CRC had been reported to have increased. Despite the concerted effort in the primary prevention and widespread use of colonoscopy, to our knowledge, there have been no reports of the prevalence rate of CRC among colonoscopy recipients from Oman. This study aims to explore the CRC prevalence estimates over selected sociodemographic characteristics among colonoscopy-recipients at a tertiary hospital in Oman over five years of follow-up. The regional variations in Oman were also examined in this study. METHODS: This hospital-based cross-sectional study reviewed reports of colonoscopies performed over 5-years of retrospective follow-up at a tertiary hospital in Oman. CRC prevalence estimates were calculated over age, gender, governorate, and time of follow-up. RESULTS: A total of 442 CRC cases were enumerated among 3701 colonoscopies, with an overall CRC prevalence estimate of 11.9 per 100 colonoscopies (95% CI: 10.9, 13.0). Gender-specific CRC prevalence was higher among males compared with females (13.3 vs. 10.5). Age-specific CRC prevalence increased with advancing age, from 2.8 among those less than 40 years of age to 26.5 among aged 70 years or more. Regional CRC prevalence was highest among residents in Batinah Governorate. Over the 5-years of follow-up, there was a slow rise in CRC prevalence with an annual increment of 0.59%. CONCLUSION: The study provides supportive evidence for a steady increase in CRC prevalence over age categories and years of follow-up and depicted the variations of gender-specific CRC prevalence estimates over increasing age categories. The study calls for timely formulation and adoption of national CRC screening programs centered on the colonoscopy use as primary prevention and maximizing its utilization and efficiency.
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Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Centros de Atenção Terciária , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/história , Estudos Transversais , Detecção Precoce de Câncer , Feminino , História do Século XXI , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Omã/epidemiologia , Prevalência , Vigilância em Saúde Pública , Estudos RetrospectivosRESUMO
OBJECTIVES: Triple-negative breast cancer (TNBC) is one of the most aggressive and heterogeneous variants of breast cancer. However, little is known regarding the prevalence and outcome of this entity in the Middle East. This study aimed to evaluate the outcomes of TNBC patients at a university hospital in Oman. METHODS: This retrospective study took place at the Sultan Qaboos University Hospital, Muscat, Oman, in May 2017. All patients diagnosed with non-metastatic TNBC between December 2000 and December 2015 were included. The patients' electronic medical records were reviewed to identify their clinical and pathological characteristics as well as survival outcomes. RESULTS: A total of 79 patients were diagnosed with non-metastatic TNBC during the study period. The median age was 46 years, with approximately one-third of patients (31.6%) under 40 years of age. Almost half had an advanced tumour size (49.4%) or node-positive disease (48.1%) at presentation and only 16.6% demonstrated a complete pathological response (pCR) to neoadjuvant chemotherapy. The median survival for all patients was not reached within the study period; however, the median overall survival for stage III patients was 44.6 months. The five-year overall survival for all patients was 64%, increasing to 100% and 72% for patients with stage I and II, respectively, and dropping to 47% for those with stage III disease. CONCLUSION: The findings of this study indicate that the majority of women with TNBC in Oman present at an advanced stage; moreover, such women have low rates of pCR to neoadjuvant chemotherapy and poor five-year survival.
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Recidiva Local de Neoplasia/mortalidade , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/sangue , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Omã/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Circulating proteins hold a potential benefit as biomarkers for precision medicine. Previously, we showed that systemic levels of neuropilin-1 (NRP-1) and its associated molecules correlated with poor-prognosis breast cancer. To further identify the role of NRP-1 and its interacting molecules in correspondence with patients' response to neoadjuvant chemotherapy (NAC), we conducted a comparative study on blood and tissue samples collected from a cohort of locally advanced breast cancer patients, before and after neoadjuvant chemotherapy (NAC). From a panel of tested proteins and genes, we found that the levels of plasma NRP-1, placenta growth factor (PlGF) and immune cell expression of the transcription factor SNAI1 before and after NAC were significantly different. Paired t-test analysis of 22 locally advanced breast cancer patients showed that plasma NRP-1 levels were increased significantly (p = 0.018) post-NAC in patients with pathological partial response (pPR). Kaplan-Meier analysis indicated that patients who received NAC cycles and their excised tumors remained with high levels of NRP-1 had a lower overall survival compared with patients whose tissue NRP-1 decreased post-NAC (log-rank p = 0.049). In vitro validation of the former result showed an increase in the secreted and cellular NRP-1 levels in resistant MDA-MB-231 cells to the most common NAC regimen Adriyamicin/cyclophosphamide+Paclitaxel (AC+PAC). In addition, NRP-1 knockdown in MDA-MB-231 cells sensitized the cells to AC and more profoundly to PAC treatment and the cells sensitivity was proportional to the expressed levels of NRP-1. Unlike NRP-1, circulating PlGF was significantly increased (p = 0.014) in patients with a pathological complete response (pCR). SNAI1 expression in immune cells showed a significant increase (p = 0.018) in patients with pCR, consistent with its posited protective role. We conclude that increased plasma and tissue NRP-1 post-NAC correlate with pPR and shorter overall survival, respectively. These observations support the need to consider anti-NRP-1 as a potential targeted therapy for breast cancer patients who are identified with high NRP-1 levels. Meanwhile, the increase in both PlGF and SNAI1 in pCR patients potentially suggests their antitumorigenic role in breast cancer that paves the way for further mechanistic investigation to validate their role as potential predictive markers for pCR in breast cancer.
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OBJECTIVES: The incidence of lung cancer in Oman has shown a gradual but definitive increase since 2002. This study aimed to evaluate the demographic and epidemiological characteristics and survival outcomes of patients with non-small-cell lung cancer (NSCLC) at a university hospital in Oman. METHODS: This study was conducted from January to June 2016. A retrospective analysis was performed of consecutive patients diagnosed with NSCLC presenting to the Sultan Qaboos University Hospital (SQUH) in Muscat, Oman, between March 2000 and December 2015. Clinical features at presentation and prognostic and predictive markers were reviewed. Kaplan-Meir estimates were used to determine relapse-free survival, progression-free survival (PFS) and overall survival (OS). RESULTS: A total of 104 patients presented to SQUH during the study period. The median age at diagnosis was 64 years. Overall, 62 patients (59.6%) had adenocarcinomas. Only 12 patients (11.5%) presented in the early stages (I or II) of the disease and the majority of patients had an Eastern Cooperative Oncology Group performance status of 1 (27.9%) or 2 (26.0%). The prevalence of epidermal growth factor receptor mutations was 27.9%. The median PFS for patients with advanced disease (stages III or IV) was five months and the median OS for all patients was seven months. After five years, 50.0%, 60.0%, 10.0% and 8.0% of patients with disease stages I, II, III and IV, respectively, were alive. CONCLUSION: Patients with NSCLC in Oman were found to present at an advanced stage. However, patient outcomes were similar to those reported in the USA.
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Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Omã/epidemiologia , Estudos RetrospectivosRESUMO
Breast and ovarian cancer are heterogeneous diseases. While breast cancer accounts for 25% of cancers worldwide, ovarian cancer accounts for 3.5% of all cancers and it is considered to be the most lethal type of cancer among women. In Oman, breast cancer accounts for 25% and ovarian cancer for 4.5% of all cancer cases. Various risk factors, including variable biological and clinical traits, are involved in the onset of breast and ovarian cancer. Although highly developed diagnostic and therapeutic methods have paved the way for better management, targeted therapy against specific biomarkers has not yet shown any significant improvement, particularly in triple-negative breast cancer and epithelial ovarian cancer, which are associated with high mortality rates. Thus, elucidating the mechanisms underlying the pathology of these diseases is expected to improve their prevention, prognosis and management. The aim of the present study was to provide a comprehensive review and updated information on genomics and proteomics alterations associated with cancer pathogenesis, as reported by several research groups worldwide. Furthermore, molecular research in our laboratory, aimed at identifying new pathways involved in the pathogenesis of breast and ovarian cancer using microarray and chromatin immunoprecipitation (ChIP), is discussed. Relevant candidate genes were found to be either up- or downregulated in a cohort of breast cancer cases. Similarly, ChIP analysis revealed that relevant candidate genes were regulated by the E2F5 transcription factor in ovarian cancer tissue. An ongoing study aims to validate these genes with a putative role as biological markers that may contribute to the development of targeted therapies for breast and ovarian cancer.
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Circulating plasma and peripheral blood mononuclear (PBMCs) cells provide an informative snapshot of the systemic physiological state. Moreover, they provide a non-invasively accessible compartment to identify biomarkers for personalized medicine in advanced breast cancer. The role of Neuropilin-1 (NRP-1) and its interacting molecules in breast tumor tissue was correlated with cancer progression; however, the clinical impact of their systemic levels was not extensively evaluated. In this cross-sectional study, we found that circulating and tumor tissue expression of NRP-1 and circulating placental growth factor (PlGF) increase in advanced nodal and metastatic breast cancer compared with locally advanced disease. Tumor tissue expression of NRP-1 and PlGF is also upregulated in triple negative breast cancer (TNBC) compared to other subtypes. Conversely, in PBMCs, NRP-1 and its interacting molecules SEMA4A and SNAI1 are significantly downregulated in breast cancer patients compared to healthy controls, indicating a protective role. Moreover, we report differential PBMC expression profiles that correlate inversely with disease stage (SEMA4A, SNAI1, PLXNA1 and VEGFR3) and can differentiate between the TNBC and non-TNBC tumor subtypes (VEGFR3 and PLXNA1). This work supports the importance of NRP-1-associated molecules in circulation to characterize poor prognosis breast cancer and emphasizes on their role as favorable drug targets.
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Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neuropilina-1/sangue , Adulto , Idoso , Neoplasias da Mama/genética , Estudos de Coortes , Estudos Transversais , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Leucócitos Mononucleares/metabolismo , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Fator de Crescimento Placentário/sangue , Prognóstico , Carga Tumoral , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: The incidence of breast cancer is rising in Oman, and the disease is diagnosed at late stages, when treatment success is limited. Omani women might benefit from better awareness, so that breast cancer can be detected early and treated. This study was conducted to assess Omani women's levels of breast cancer awareness and early detection practice, and explore factors which might influence these levels. MATERIALS AND METHODS: A mixed methods study was conducted in 2014, including a quantitative survey of 1,372 and a qualitative assessment of 19 Omani women, aged ≥20 years from five Omani governorates using convenient sampling. Demographic information and scores for awareness levels were used in a multivariate regression model to investigate factors associated with awareness. Thematic analysis and interpretive description were used to analyse the qualitative data. RESULTS: The overall means for early detection and general awareness scores were 0.58 (SD 0.24) and 0.46 (SD 0.21), respectively. General awareness was significantly associated with age, education, income and familiarity with cancer patients (<0.05), while early detection was significantly associated with age, marital status and education. A majority of women (59.5%) agreed with a belief in 'evil eye' or envy as a risk factor for breast cancer. Women discussed various factors which may empower or inhibit awareness, including the cultural-religion-fatalistic system, personal-familial-environmental system, and healthcare-political-social system. CONCLUSIONS: The overall low scores for awareness and early detection, and the survey of local beliefs highlight a severe necessity for a contextually-tailored breast cancer awareness intervention programme in Oman.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Detecção Precoce de Câncer/estatística & dados numéricos , Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Adulto , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer/psicologia , Escolaridade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Omã/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde , Prognóstico , Religião , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
INTRODUCTION: MicroRNAs (miRNAs) are small non-coding RNA that plays a vital role in cancer progression. Neo-adjuvant chemotherapy (NAC) has become the standard of care for locally advanced breast cancer. The aim of this study was to evaluate miRNA alterations during NAC using multiple samples of tissue and serum to correlate miRNA expression with clinico-pathological features and patient outcomes. METHODS: Tissue and serum samples were collected from patients with locally advanced breast cancer undergoing NAC at four time points: time of diagnosis, after the first and fourth cycle of doxorubicin/cyclophosphamide treatment, and after the fourth cycle of docetaxel administration. First, we evaluated the miRNA expression profiles in tissue and correlated expression with clinico-pathological features. Then, a panel of four miRNAs (miR-451, miR-3200, miR-21, and miR-205) in serum samples was further validated using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). The alterations in serum levels of miRNA, associations with clinical and pathological responses, correlation with clinico-pathological features, and survival outcomes were studied using Friedman, Mann-Whitney U, and Spearman, Wilcoxon signed-ranks tests. P≤0.05 was considered statistically significant. RESULTS: We analyzed 72 tissue samples and 108 serum samples from 9 patients and 27 patients, respectively. MicroRNA expression profiling of tumor versus normal tissue revealed more than 100 differentially expressed miRNAs. Serum miR-451 levels were significantly decreased during treatment, and higher serum levels were associated with improved clinical and pathological responses and disease-free survival. This is one of the early reports on miR-3200 in response to treatment in breast cancer, as serum levels of miR-3200 found to decline during NAC, and higher serum levels were associated with lower residual breast cancer burden and relapse rates at time of diagnosis. CONCLUSION: Variations in serum miRNA levels during NAC treatment may be therapeutically significant for predicting response and survival outcomes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , Terapia Neoadjuvante , Adulto , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Taxa de Sobrevida , Taxoides/administração & dosagem , Trastuzumab/administração & dosagemRESUMO
Breast cancer (BC) arises commonly in women with metabolic dysfunction. The underlying mechanism by which glycemic load can exert its action on tumor metastasis is under investigated. In this study we showed that glycemic microenvironment alters the expression of three classes of proteins, VEGF and its receptors, cell to cell, and cell to extracellular matrix (ECM) adhesion proteins in MDA-MB-231 parental cells and its two metastatic variants to the bone and brain (MDA-MB-231BO and MDA-MB-231BR, respectively). Using western blotting, we showed that VEGFR2 levels were higher in these variant cells and persisted in the cells under extreme hypoglycemia. Hypoglycemia did not alter VEGFR2 expression per se but rather suppressed its posttranslational glycosylation. This was reversed rapidly upon the restoration of glucose, and cyclohexamide (CHX) treatment demonstrated that this deglycosylated VEGFR2 was not a product of de-novo protein synthesis. VEGFR2 co-receptor Neuropilin-1 was up-regulated four-fold in all MDA-MB-231 cells (parental and two variants) compared to VEGFR2 expression, and was also susceptible to glycemic changes but resistant to CHX treatment for up to 72 hrs. Hypoglycemia also resulted in a significant decrease in specific catenin, cadherin, and integrin proteins, as well as cellular proliferation and colony forming ability. However, MDA-MB-231BR cells showed a unique sensitivity to hypo/hyperglycemia in terms of morphological changes, colony formation ability, integrin ß3 expression and secreted VEGF levels. In conclusion, this study can be translated clinically to provide insight into breast cancer cell responses to glycemic levels relevant for our understanding of the interaction between diabetes and cancer.
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Neoplasias da Mama/patologia , Proteínas da Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Hiperglicemia/fisiopatologia , Hipoglicemia/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Apoptose , Western Blotting , Neoplasias da Mama/etiologia , Neoplasias da Mama/metabolismo , Proliferação de Células , Progressão da Doença , Proteínas da Matriz Extracelular/genética , Feminino , Humanos , Hiperglicemia/complicações , Hipoglicemia/complicações , Técnicas Imunoenzimáticas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ativação Transcricional , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
INTRODUCTION: Central venous catheters play an important role in the management of cancer patients. Different types of devices are associated with different patterns of complications. We report on the pattern of use and rate of complications of port-a-caths in patients diagnosed with malignant cancer at a single institution. METHODOLOGY: The data were collected retrospectively from patients who received the treatment for solid tumors or lymphoma through a port-a-cath at the Sultan Qaboos University Hospital (SQUH) between January 2007 and February 2013. RESULTS: A total of 117 port-a-caths were inserted in 106 patients. The majority (86; 73.5%) were implanted by an interventional radiologist, and the right internal jugular vein was accessed in 79 (67.5%) patients. Mean catheter indwelling time was 354 (range 3-1,876) days for all patients, 252 (3-1,876) and 389 days (13-1,139) for patients with and without complications, respectively. Thirty (25.6%) port-a-caths were removed prematurely, mainly due to infectious complications, while 17 (14.5%) were removed after completion of treatment. Staphylococcus aureus was the most frequently isolated organism, found in 8 (6.8%) patients. Underlying diagnosis (p < 0.001), chemotherapy regimen (p < 0.001), sensitivity to antibiotics (p = 0.01), and any complication (p < 0.001) were significant factors affecting the duration of port-a-cath use. None of these factors were significant on multivariate cox regression analysis. CONCLUSIONS: The mean duration of port-a-cath use was almost one year. Infection was the most common complication leading to premature removal, followed by port thrombosis.
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Cateterismo Venoso Central/estatística & dados numéricos , Neoplasias/terapia , Dispositivos de Acesso Vascular/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Cateteres de Demora/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Omã , Estudos Retrospectivos , Trombose/epidemiologia , Dispositivos de Acesso Vascular/efeitos adversos , Adulto JovemRESUMO
Wilms' tumour is common among children but rare in adults. Children with Wilms' tumour have better prognosis even when diagnosed at advanced stage. We report the case of an adolescent girl with chemo-resistant metastatic Wilms' tumour treated previously with two lines of chemotherapy. Upon progression on second line chemotherapy, there was a partial response to Bevacizumab based combination chemotherapy in the third line. Patient was referred for high dose chemotherapy and autologous stem cell therapy. The latter could not be achieved. The patient had a relapse 3 months later and succumbed to the disease.
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Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Tumor de Wilms/tratamento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Evolução Fatal , Feminino , Humanos , Neoplasias Renais/patologia , Metastasectomia , Recidiva Local de Neoplasia/patologia , Tumor de Wilms/patologiaAssuntos
Sarcoma de Ewing/diagnóstico , Neoplasias Vaginais/diagnóstico , Adulto , Evolução Fatal , Feminino , HumanosRESUMO
Cisplatin is commonly used against several solid tumors, and oxaliplatin is an effective cytotoxic drug used in colorectal cancer. A major clinical issue affecting 10-40 % of patients treated with cisplatin or oxaliplatin is severe peripheral neuropathy causing sensory, motor, and autonomic dysfunction, with symptoms including cold sensitivity and neuropathic pain. The biochemical basis of the neurotoxicity is uncertain, but is associated with oxidative stress. Curcumin (a natural phenolic yellow pigment) has strong antioxidant, anticancer, and anti-inflammatory actions. Here we report the possible protective effect of curcumin on some cisplatin- and oxaliplatin-induced behavioral, biochemical, and histopathological alterations in rats. Twenty-four hours after the end of treatments some motor and behavioral tests (motor activity, thermal and mechanical nociception, and neuromuscular coordination) were conducted, followed by measuring plasma neurotensin platinum concentration in the sciatic nerve, and studying the histopathology of the sciatic nerve. Oxaliplatin (4 mg/kg) and cisplatin (2 mg/kg) [each given twice weekly, in a total of nine intraperitoneal injections over 4.5 weeks] significantly increased plasma neurotensin concentration, caused specific damage in the histology of the sciatic nerve and produced variable effects in the motor and behavioral tests. Oral curcumin (10 mg/kg, 4 days before the platinum drug, and thereafter, concomitantly with it for 4.5 weeks) reversed the alterations in the plasma neurotensin and sciatic nerve platinum concentrations, and markedly improved sciatic nerve histology in the platinum-treated rats. Larger experiments using a wider dose range of oxaliplatin, cisplatin, and curcumin are required to fully elucidate the possible protective role of curcumin in platinum-induced neurotoxicity.
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Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/toxicidade , Comportamento Animal/efeitos dos fármacos , Cisplatino/toxicidade , Curcumina/farmacologia , Doenças do Sistema Nervoso/prevenção & controle , Compostos Organoplatínicos/toxicidade , Administração Oral , Animais , Comportamento Animal/fisiologia , Modelos Animais de Doenças , Masculino , Atividade Motora/efeitos dos fármacos , Doenças do Sistema Nervoso/induzido quimicamente , Doenças do Sistema Nervoso/fisiopatologia , Neurotensina/metabolismo , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/tratamento farmacológico , Dor Nociceptiva/fisiopatologia , Oxaliplatina , Sistema Nervoso Periférico/efeitos dos fármacos , Sistema Nervoso Periférico/patologia , Sistema Nervoso Periférico/fisiopatologia , Ratos , Ratos Wistar , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo , Nervo Isquiático/patologiaRESUMO
UNLABELLED: Breast cancer is the most common cancer worldwide with significant global burden. Insulin-like growth factor 1 (IGF1) is an important regulator of cellular growth, differentiation, and apoptosis and mitogenic and antiapoptotic activities. Some studies suggested an association between cytosine adenine (CA) repeats gene polymorphisms of IGF1 and the risk of developing breast cancer while other studies did not find such an association. This study aims investigate the role of IGF1 (CA) repeats gene polymorphisms in the risk of developing breast cancer among Omani women. METHODS: We analyzed (CA) repeats gene polymorphisms of IGF1 by extraction of genomic DNA from the peripheral blood of 147 patients with breast cancer and 134 control participants and performed genotyping using DNA sequencing. RESULTS: Approximately 46% of patients carried the IGF (CA)(19) repeat allele, with 31.3% carrying two copies of this allele and 50% of controls carried the IGF (CA)(19) repeat allele with 30.1% carrying two copies of this allele. The difference of the IGF CA repeat groups was significant between cases and controls with (P =0.02). In contrast, there was no difference in the distribution of (CA)(19) repeat allele, (CA)(18) repeat allele and (CA)(19) repeat allele between cases and controls. The difference of the CA groups was significant between cases and controls among postmenopausal women with (P =0.026), whereas no difference was observed among postmenopausal subjects (P =0.429). In both pre- and postmenopausal groups there was no difference in the distribution of (CA)(19) repeat allele, (CA)(18) repeat allele and (CA)(20) repeat allele between patients and control subjects. On further IGF1 genotypes classification, we found an association between progesterone receptor status and the genotypes group where the non carrier of (CA)(19) repeat group was compared to (CA)(19) repeat carrier group (OR =2.482; 95% CI =1.119-5.503; P value =0.023). CONCLUSION: Overall there was no association between the IGF (CA)(19) repeat and breast cancer in Omani females.
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AIM: We carried out a case-control study in an Omani Arab population to investigate the association between gastric cancer and peripheral blood leukocyte DNA methylation in LINE-1 and in the tumor suppressor genes CDH1, p16, TP53 and RUNX3. MATERIALS & METHODS: We quantified methylation (%5-mC) in DNA extracted from peripheral blood leukocytes via pyrosequencing. We calculated odds ratios (ORs) and 95% CIs using logistic regression. RESULTS: We found patterns of global hypomethylation (LINE-1: OR(continuous) = 0.59; 95% CI: 0.42-0.82) and TP53 promoter hypomethylation (OR(continuous) = 0.64; 95% CI: 0.16-0.85) for cases versus controls; p16 promoter region hypomethylation was not statistically significant. Evaluating LINE-1, TP53 and p16 jointly yielded a more pronounced negative association with gastric cancer (OR: 0.24; 95% CI: 0.09-0.66). Age was a significant effect modifier. We found no differences by tumor grade, stage or histology. CONCLUSION: We found a pattern of global hypomethylation and promoter region hypomethylation of TP53 and p16 in cases versus controls for this population of Omani Arabs.