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1.
PLoS One ; 17(12): e0277143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36574417

RESUMO

Improving outcomes for people undergoing major surgery, specifically reducing perioperative morbidity and mortality remains a global health challenge. Prehabilitation involves the active preparation of patients prior to surgery, including support to tackle risk behaviours that mediate and undermine physical and mental health and wellbeing. The majority of prehabilitation interventions are delivered in person, however many patients express a preference for remotely-delivered interventions that provide them with tailored support and the flexibility. Digital prehabilitation interventions offer scalability and have the potential to benefit perioperative healthcare systems, however there is a lack of robustly developed and evaluated digital programmes for use in routine clinical care. We aim to systematically develop and test the feasibility of an evidence and theory-informed multibehavioural digital prehabilitation intervention 'iPREPWELL' designed to prepare patients for major surgery. The intervention will be developed with reference to the Behaviour Change Wheel, COM-B model, and the Theoretical Domains Framework. Codesign methodology will be used to develop a patient intervention and accompanying training intervention for healthcare professionals. Training will be designed to enable healthcare professionals to promote, support and facilitate delivery of the intervention as part of routine clinical care. Patients preparing for major surgery and healthcare professionals involved with their clinical care from two UK National Health Service centres will be recruited to stage 1 (systematic development) and stage 2 (feasibility testing of the intervention). Participants recruited at stage 1 will be asked to complete a COM-B questionnaire and to take part in a qualitative interview study and co-design workshops. Participants recruited at stage 2 (up to twenty healthcare professionals and forty participants) will be asked to take part in a single group intervention study where the primary outcomes will include feasibility, acceptability, and fidelity of intervention delivery, receipt, and enactment. Healthcare professionals will be trained to promote and support use of the intervention by patients, and the training intervention will be evaluated qualitatively and quantitatively. The multifaceted and systematically developed intervention will be the first of its kind and will provide a foundation for further refinement prior to formal efficacy testing.


Assuntos
Exercício Pré-Operatório , Medicina Estatal , Humanos , Estudos de Viabilidade , Pacientes , Saúde Mental
2.
World J Surg ; 44(5): 1547-1551, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32002582

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) can improve cosmesis by reducing resection volume. Breast-conserving surgery (BCS) aims to achieve clear excision margins while optimizing cosmesis. However, the influence of NAC on margin re-excision after BCS is unclear. This study examines the rate and determinants of margin re-excision in patients undergoing BCS following NAC in our institution. METHODS: From 2011-2015, all patients treated with NAC prior to BCS were identified from a prospectively maintained database. Mann-Whitney and Fisher's exact test tests were used to compare variables in patients who did and did not require re-excision. Patients undergoing primary surgical treatment in 2015 comprised an unmatched comparison group. RESULTS: Of 211 patients treated with NAC, 69 initially underwent BCS. The re-excision rate was 32% (n = 22) compared to 17% in the primary operable group (38 of 221, p = 0.02). Re-excision rates were lowest in triple-negative and HER2+ tumors (0% and 10%, respectively). Lobular carcinoma and ER+ tumors had a significantly higher rate of re-excision (100% and 42%, respectively). Of 22 patients undergoing re-excision, 9 had further BCS and 13 had a mastectomy. CONCLUSION: The re-excision rate following NAC is almost twice that of patients who underwent primary operative management. Her2+ and triple-negative tumors have lower re-excision rates and may represent a selected cohort most suitable for BCS. Patients with invasive lobular carcinoma or ER+ disease have significantly higher rates of margin positivity, and these patients should be considered for a cavity shave during primary surgery to reduce the rates of re-excision.


Assuntos
Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Terapia Neoadjuvante , Reoperação , Neoplasias de Mama Triplo Negativas/cirurgia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/metabolismo , Feminino , Humanos , Margens de Excisão , Mastectomia Segmentar , Pessoa de Meia-Idade , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Estudos Retrospectivos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
3.
Ann R Coll Surg Engl ; 101(4): 268-272, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30855173

RESUMO

INTRODUCTION: Although close radial margins after breast-conserving surgery routinely undergo re-excision, appropriate management of patients with close anterior margins remains a topic of controversy. An increasing body of literature suggests that re-excision of close anterior margins yields low rates of residual malignancy and may only be necessary in selected patients. The aim of this study was to examine the management of close anterior margins after breast conserving surgery in a single institution and to analyse the rate of residual disease in re-excised anterior margins. METHODS: All patients having breast conserving surgery at St Vincent's University Hospital from January 2008 to December 2012 were reviewed retrospectively. Data collected included patient demographics, tumour characteristics, margin positivity, re-excision rates and definitive histology of the re-excision specimens. A close margin was defined as les than 2 mm. RESULTS: A total of 930 patients were included with an average age of 65 years (range 29-94 years). Of these, 121 (13%) had a close anterior margin. Further re-excison of the anterior margin was carried out in 37 patients (30.6%) and a further 16 (13.2%) proceeded to mastectomy. Residual disease was found in 18.5% (7/36) of those who underwent re-excision and 7/16 (43.75%) of those who underwent mastectomy. Overall, 11.57% (14/121) of patients with close anterior margins were subsequently found to have residual disease. CONCLUSION: The low yield of residual disease in re-excised anterior margins specimens supports the concept that routine re-excision of close anterior margins is not necessary. Further research is required to definitively assess its influence on the risk of local recurrence.


Assuntos
Margens de Excisão , Mastectomia Segmentar , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos
4.
Reproduction ; 156(2): R9-R21, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29717022

RESUMO

Infertility is an often devastating diagnosis encountered by around one in six couples who are trying to conceive. Moving away from the long-held belief that infertility is primarily a female issue, it is now recognised that half, if not more, of these cases may be due to male factors. Recent evidence has suggested that epigenetic abnormalities in chromatin dynamics, DNA methylation or sperm-borne RNAs may contribute to male infertility. In light of advances in deep sequencing technologies, researchers have been able to increase the coverage and depth of sequencing results, which in turn has allowed more comprehensive analyses of spermatozoa chromatin dynamics and methylomes and enabled the discovery of new subsets of sperm RNAs. This review examines the most current literature related to epigenetic processes in the male germline and the associations of aberrant modifications with fertility and development.


Assuntos
Reprogramação Celular , Epigênese Genética , Infertilidade Masculina/etiologia , Espermatogênese , Animais , Metilação de DNA , Humanos , Masculino , RNA Longo não Codificante/metabolismo , Espermatozoides/metabolismo
5.
Eur J Nutr ; 57(1): 309-318, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27743129

RESUMO

PURPOSE: The Oral Fat Tolerance Test (OFTT) is regarded as a repeatable measure used to assess postprandial triglyceride (TAG) levels, with higher levels observed in cardio-metabolic disorders. Acute aerobic exercise intervention before OFTT reduces the TAG response, but the repeatability of this effect is unknown. The aim of this study was to determine the repeatability of the abbreviated 4-h OFTT with and without immediate prior aerobic exercise. METHODS: On four separate days, healthy adult male participants underwent two 4-h OFTT (n = 10) and another two 4-h OFTT with 1-h of standardised moderate intensity aerobic exercise performed immediately before meal ingestion (n = 11). The OFTT meal composition included 75.4 g total fat, 21.7 g carbohydrate and 13.7 g protein. Venous blood was sampled at baseline and hourly up to 4 h after the OFTT meal ingestion, and TAG area under the curve (AUC) was calculated. RESULTS: Nonparametric Bland-Altman analysis of 4-h TAG AUC revealed that 9 of 10 repeat measurements fell within ±15 % of the median TAG AUC for the OFTT. By contrast, two of 11 repeat measurements fell within ±15 % of the median TAG AUC for the OFTT undertaken with 1-h prior aerobic exercise. CONCLUSIONS: The 4-h OFTT is a repeatable test of postprandial TAG responses in healthy men. However, aerobic exercise performed immediately before OFTT considerably increases the variability of TAG AUC. These findings have implications for interpretation of research studies investigating exercise intervention performed immediately before OFTT. Future studies should also investigate the repeatability of exercise performed 8-24 h before OFTT.


Assuntos
Gorduras na Dieta/administração & dosagem , Exercício Físico/fisiologia , Triglicerídeos/sangue , Adulto , Apolipoproteínas B/sangue , Área Sob a Curva , Glicemia/análise , Estudos Cross-Over , Carboidratos da Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Humanos , Insulina/sangue , Masculino , Refeições , Período Pós-Prandial/fisiologia , Estudos Prospectivos , Reprodutibilidade dos Testes
6.
Reprod Fertil Dev ; 29(9): 1729-1738, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27651295

RESUMO

The endometrium plays a key role in providing an optimal environment for attachment of the preimplantation embryo during the early stages of pregnancy. Investigations over the past 2 decades have demonstrated that vital epigenetic processes occur in the embryo during the preimplantation stages of development. However, few studies have investigated the potential role of imprinted genes and their associated modulators, the DNA methyltransferases (DNMTs), in the bovine endometrium during the pre- and peri-implantation period. Therefore, in the present study we examined the expression profiles of the DNMT genes (3A, 3A2 and 3B) and a panel of the most comprehensively studied imprinted genes in the endometrium of cyclic and pregnant animals. Intercaruncular (Days 5, 7, 13, 16 and 20) and caruncular (Days 16 and 20) regions were analysed for gene expression changes, with protein analysis also performed for DNMT3A, DNMT3A2 and DNMT3B on Days 16 and 20. An overall effect of day was observed for expression of several of the imprinted genes. Tissue-dependent gene expression was detected for all genes at Day 20. Differences in DNMT protein abundance were mostly observed in the intercaruncular regions of pregnant heifers at Day 16 when DNMT3A, DNMT3A2 and DNMT3B were all lower when compared with cyclic controls. At Day 20, DNMT3A2 expression was lower in the pregnant caruncular samples compared with cyclic animals. This study provides evidence that epigenetic mechanisms in the endometrium may be involved with implantation of the embryo during the early stages of pregnancy in cattle.


Assuntos
DNA (Citosina-5-)-Metiltransferases/genética , Implantação do Embrião/fisiologia , Endométrio/metabolismo , Expressão Gênica , Animais , Blastocisto/metabolismo , Bovinos , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , DNA Metiltransferase 3A , Desenvolvimento Embrionário/fisiologia , Feminino , Perfilação da Expressão Gênica , Gravidez
7.
Ir J Med Sci ; 186(1): 63-67, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27271165

RESUMO

BACKGROUND: Breast cancer in women under 40 years of age is rare and typically presents symptomatically. The optimal imaging modality for this patient group is controversial. Most women undergo ultrasonography with/without mammography. Young women typically have dense breasts, which can obscure the features of malignancy on film mammography, however, initial studies have suggested that digital mammography may have a more accurate diagnostic performance in younger women. Ultrasound generally performs well in this age group, although it is poor at detecting carcinoma in situ (DCIS). AIMS: To evaluate the comparative diagnostic performance of ultrasonography and digital mammography in the initial diagnostic evaluation of women under 40 years of age with symptomatic breast cancer. METHODS: Retrospective review of all women under the age of 40 years managed at our symptomatic breast cancer unit from January 2009 to December 2015. RESULTS: There were 120 patients that met the inclusion criteria for this study. The sensitivity of ultrasonography and digital mammography for breast cancer in this patient group was 95.8 and 87.5 %, respectively. The patients with a false negative mammographic examination were more likely to have dense breasts (p < 0.01). Five patients had a false negative ultrasonographic examination, withal of whom were diagnosed with DCIS detected by mammography. CONCLUSION: This study demonstrates the superior sensitivity of ultrasound for breast cancer in women under the age of 40 years, however, the results show that digital mammography has an important complimentary role in the comprehensive assessment of these patients, particularly in the diagnosis of DCIS.


Assuntos
Neoplasias da Mama/diagnóstico , Mamografia/métodos , Ultrassonografia Mamária/métodos , Adulto , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Carcinoma in Situ/diagnóstico por imagem , Feminino , Humanos , Estudos Retrospectivos , Sensibilidade e Especificidade
8.
BMC Genomics ; 17(1): 1004, 2016 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-27931182

RESUMO

BACKGROUND: Metabolic stress associated with negative energy balance in high producing dairy cattle and obesity in women is a risk factor for decreased fertility. Non-esterified fatty acids (NEFA) are involved in this pathogenesis as they jeopardize oocyte and embryo development. Growing evidence indicates that maternal metabolic disorders can disturb epigenetic programming, such as DNA methylation, in the offspring. Oocyte maturation and early embryo development coincide with methylation changes and both are sensitive to adverse environments. Therefore, we investigated whether elevated NEFA concentrations affect establishment and maintenance of DNA methylation in oocytes and embryos, subsequently altering transcriptomic profiles and developmental competence of resultant blastocysts. RESULTS: Bovine oocytes and embryos were exposed to different NEFA concentrations in separate experiments. In the first experiment, oocytes were matured in vitro for 24 h in medium containing: 1) physiological ("BASAL") concentrations of oleic (OA), palmitic (PA) and stearic (SA) acid or 2) pathophysiological ("HIGH COMBI") concentrations of OA, PA and SA. In the second experiment, zygotes were cultivated in vitro for 6.5 days under BASAL or HIGH COMBI conditions. Developmental competence was evaluated by assessing cleavage and blastocyst rate. Overall gene expression and DNA methylation of resultant blastocysts were analyzed using microarray. DNA methylation data were re-evaluated by pyrosequencing. HIGH COMBI-exposed oocytes and embryos displayed a lower competence to develop into blastocysts compared to BASAL-exposed counterparts (19.3% compared to 23.2% and 18.2% compared to 25.3%, respectively) (P < 0.05). HIGH COMBI-exposed oocytes and embryos resulted in blastocysts with altered DNA methylation and transcriptomic fingerprints, compared to BASAL-exposed counterparts. Differences in gene expression and methylation were more pronounced after exposure during culture compared to maturation suggesting that zygotes are more susceptible to adverse environments. Main gene networks affected were related to lipid and carbohydrate metabolism, cell death, immune response and metabolic disorders. CONCLUSIONS: Overall, high variation in methylation between blastocysts made it difficult to draw conclusions concerning methylation of individual genes, although a clear overview of affected pathways was obtained. This may offer clues regarding the high rate of embryonic loss and metabolic diseases during later life observed in offspring from mothers displaying lipolytic disorders.


Assuntos
Blastocisto/metabolismo , Embrião de Mamíferos/metabolismo , Epigênese Genética/efeitos dos fármacos , Ácidos Graxos não Esterificados/toxicidade , Oócitos/metabolismo , Transcriptoma/efeitos dos fármacos , Animais , Bovinos , DNA/química , DNA/isolamento & purificação , DNA/metabolismo , Metilação de DNA/efeitos dos fármacos , Embrião de Mamíferos/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Histonas/genética , Análise de Sequência com Séries de Oligonucleotídeos , Oócitos/efeitos dos fármacos , Análise de Sequência de DNA , Proteínas Centrais de snRNP/genética
9.
World J Surg ; 40(9): 2157-62, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27206399

RESUMO

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.


Assuntos
Biópsia por Agulha Fina , Neoplasias da Mama/patologia , Biópsia Guiada por Imagem , Linfonodos/patologia , Biópsia de Linfonodo Sentinela , Ultrassonografia de Intervenção , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
10.
Sci Rep ; 6: 24583, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27079521

RESUMO

The oviduct functions in the transportation of gametes to the site of fertilization (the ampulla) and is the site of early embryonic development. Alterations of this early developmental environment, such as the presence of sexually transmitted pathogens, may affect oviduct function leading to reduced fertilization rates and contribute to compromised embryonic development. In this study, sperm interactions, particle transport speed (PTS) and cilia beat frequency (CBF) in the ampulla following exposure to lipopolysaccharide (LPS), a constituent of the sexually transmitted pathogens Chlamydia trachomatis and Chlamydia abortus, was investigated. Three complementary experiments were performed to analyse; (1) bound sperm motility and cilia function (2) transport velocity in the oviduct and (3) the expression of genes related to immune function and inflammatory response (CASP3, CD14, MYD88, TLR4 and TRAF6). The motility of bound sperm was significantly lower in ampullae that were exposed to LPS. CBF and PTS significantly increased after treatment with LPS for 2 hours. Finally, gene expression analysis revealed that CASP3 and CD14 were significantly upregulated and TLR4 trended towards increased expression following treatment with LPS. These findings provide an insight on the impact of LPS on the oviduct sperm interaction, and have implications for both male and female fertility.


Assuntos
Cílios/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Oviductos/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Animais , Bovinos , Cílios/fisiologia , Feminino , Perfilação da Expressão Gênica , Técnicas In Vitro , Inflamação/genética , Masculino , Oviductos/fisiologia , Estresse Oxidativo/genética
11.
Br J Surg ; 103(7): 839-44, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27004443

RESUMO

BACKGROUND: The majority of women with breast cancer present with localized disease. The optimal strategy for identifying patients with metastatic disease at diagnosis remains unclear. The aim of this study was to evaluate the additional diagnostic yield from isotope bone scanning when added to CT staging of the thorax, abdomen and pelvis (CT-TAP) in patients with newly diagnosed breast cancer. METHODS: All patients diagnosed with breast cancer who underwent staging CT-TAP and bone scan between 2011 and 2013 were identified from a prospective database of a tertiary referral breast cancer centre that provides a symptomatic and population-based screening breast service. Criteria for staging included: biopsy-proven axillary nodal metastases; planned neoadjuvant chemotherapy or mastectomy; locally advanced or inflammatory breast cancer and symptoms suggestive of metastases. RESULTS: A total of 631 patients underwent staging by CT-TAP and bone scan. Of these, 69 patients (10·9 per cent) had distant metastasis at presentation, with disease confined to a single organ in 49 patients (71 per cent) and 20 (29 per cent) having metastatic deposits in multiple organs. Bone metastasis was the most common site; 39 of 49 patients had bone metastasis alone and 12 had a single isolated metastatic deposit. All but two of these were to the axial skeleton. No preoperative histological factors identified a cohort of patients at risk of metastatic disease. Omission of the bone scan in systemic staging would have resulted in a false-negative rate of 0·8 per cent. CONCLUSION: For patients diagnosed with breast cancer, CT-TAP is a satisfactory stand-alone investigation for systemic staging.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Neoplasias Primárias Múltiplas/diagnóstico por imagem
12.
Eur J Surg Oncol ; 41(5): 641-6, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25736863

RESUMO

AIMS: Women with inherited pathogenic mutations in the BRCA1 or BRCA2 genes have up to an 85% risk of developing breast cancer in their lifetime. However, only about 20% of familial breast cancer is attributed to mutations in BRCA1 and BRCA2, while a further 5-10% are attributed to mutations in other rare susceptibility genes such as TP53, STK11, PTEN, ATM and CHEK2. Despite extensive efforts to explain the missing heritability of this disease, the majority of familial clustering in breast cancer remains largely unexplained. We aim to analyze the pathology of familial cases of which no pathogenic mutation is yet identified. METHODS: We compared the pathological phenotype of BRCA1/BRCA2 negative familial breast cancer (BRCAx) to BRCA1-positive, BRCA2-positive and sporadic cases without a family history. Age-adjusted analysis is summarized in odd's ratios and confidence intervals for tumor type, grade, lymph node, ER and HER2 status. RESULTS: We found non-familial cases to be more likely to be ER positive (P = 0.041) as compared with BRCAx tumors. More cases of lobular carcinoma were found with BRCAx as compared to BRCA1 tumors (P = 0.05). After multivariate logistic regression analysis, BRCAx tumors are more likely ER positive (P = 0.001) and HER2 positive (P = 0.047) in comparison to BRCA1. Conversely, BRCAx cases are less likely to be ER positive (P = 0.02) but more likely to be HER2 positive (P = 0.021) as compared with BRCA2 tumors. CONCLUSION: Our findings suggest that BRCA1, BRCA2 and BRCAx tumors differ in phenotype from non-familial and familial BRCA1-positive and BRCA2-positive tumors. Further studies will need to be performed in this important population in order to develop strategies for early detection and prevention.


Assuntos
Neoplasias da Mama/genética , Carcinoma Ductal de Mama/genética , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Lobular/genética , Genes BRCA1 , Genes BRCA2 , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/metabolismo , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Lobular/metabolismo , Carcinoma Lobular/patologia , Feminino , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Linfonodos/patologia , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Fenótipo , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Adulto Jovem
13.
Breast ; 24(3): 278-82, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25771080

RESUMO

BACKGROUND: An association between interval breast cancers (cancer detected after a normal mammogram and before the next scheduled mammogram) and tumour aggressiveness has been postulated which may reflect their relatively poor overall prognosis. The aim of this study was to evaluate known prognostic features of screen detected breast cancers compared to interval breast cancers. METHODS: Patients diagnosed with breast cancer between January 2010 and 2013 at a single unit of the National Breast Screening Program (NBSP) in Ireland and those between the ages of 50 and 65 diagnosed at a symptomatic breast clinic were included in the study. Patients who had not had a screening mammogram within the proceeding two years or had a previous history of breast cancer were excluded. Data were retrospectively collected on patient demographics, tumour type, grade, hormone receptor status and stage of disease at presentation. RESULTS: There were 915 patients included in the study, with 92% (n = 844) diagnosed through the NBSP. Ductal carcinoma in-situ accounted for 19% (n = 160) of screen-detected breast cancers but only 2.8% of interval cancers (p < 0.05). The most common type of invasive cancer was invasive ductal carcinoma. Tumour grade was significantly higher in interval breast cancers (p < 0.05). Interval cancers were identified at a significantly higher stage (Stage 1 versus 2; p < 0.001) than screen-detected cancers. Interval breast cancers were less likely to be ER positive (76% versus 81%; p < 0.05) and significantly more likely to over-express HER2 (20% vs 10%, p < 0.05) than screen-detected cancers. CONCLUSION: This study highlights the fact that interval cancers appear to have a number of adverse prognostic markers for overall breast cancer survival when compared to women with screen-detected breast cancers. Interval cancers were more likely to be invasive, of a higher grade and stage and with a greater predominance of HER2 and triple negative molecular subtypes. Therefore this heterogeneous group of tumours may be biologically more aggressive and account disproportionately to overall breast cancer mortality.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Intraductal não Infiltrante/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Mamografia , Biomarcadores Tumorais , Neoplasias da Mama/química , Neoplasias da Mama/epidemiologia , Carcinoma Ductal de Mama/química , Carcinoma Ductal de Mama/epidemiologia , Carcinoma Intraductal não Infiltrante/química , Carcinoma Intraductal não Infiltrante/epidemiologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Irlanda , Programas de Rastreamento , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2 , Estudos Retrospectivos , Avaliação de Sintomas , Fatores de Tempo
14.
Eur J Surg Oncol ; 41(4): 559-65, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25648466

RESUMO

INTRODUCTION: Recent years have seen a dramatic shift to more conservative management of the axilla in patients with a positive sentinel lymph node biopsy (SLNB). Identification of nodal disease with positive pre-operative ultrasound guided axillary fine needle aspiration cytology (AUS/FNAC) may represent a higher axillary disease burden mandating an axillary clearance and thus an upfront SLNB may be avoided. The aims of this study were to quantify nodal burden in patients with positive pre-operative AUS/FNAC and identify patients who may have been able to avoid an axillary clearance (ALND) based on ACOSOG Z011 criteria. METHODS: A retrospective review of a prospectively maintained database identified patients with positive pre-operative AUS/FNAC between 2007 and 2012. Core biopsies were excluded. Demographic and tumour characteristics were analysed. Eligibility for ACOSOG Z011 criteria was assessed and patients who may have avoided ALND were identified. RESULTS: 432 patients were identified with positive AUS/FNAC. 85 patients were excluded leaving 347 for analysis. Median age was 56 years (22-87), median tumour size was 25 mm (1.5 mm-150 mm) and median tumour pathology was grade 3 (50%) and invasive ductal carcinoma (82%). Median number of nodes removed at ALND was 23 (1-55) with a median number of positive nodes being 4 (1-47). 134 (39%) patients had ≤2 positive nodes identified on ALND making them eligible for the ACOSOG Z011 study. When other ACOSOG Z011 exclusion factors were applied only 27 (7.8%) patients may have avoided ALND. CONCLUSIONS: Nodal positivity on AUS/FNAC is associated with higher axillary disease burden. Few patients would satisfy ACOSOG/Z011 criteria and avoid ALND making an upfront SLNB unnecessary.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/secundário , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/cirurgia , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Biópsia Guiada por Imagem , Linfonodos/diagnóstico por imagem , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela , Carga Tumoral , Ultrassonografia de Intervenção , Adulto Jovem
15.
Br J Biomed Sci ; 71(1): 6-12, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24693569

RESUMO

Recently, Campylobacter ureolyticus has been detected for the first time in the faeces of patients with acute gastroenteritis using polymerase chain reaction (PCR) techniques. Cultural isolation of C. ureolyticusis is not possible using the established selective methods for the isolation of thermophilic Campylobacter spp. from faeces. The aim of the current study is to develop a new selective medium capable of isolating C. ureolyticus from faecal samples. The newly-developed medium consists of Anaerobe Basal Agar with 10 g/L additional agar, 2 g/L sodium formate and 3 g/L sodium fumarate dibasic, to which 10 mg/L nalidixic acid, 10 mg/L amphotericin B and 20 mg/L vancomycin (NAV) are added as selective agents. Validation studies have shown that this experimental selective medium completely inhibits growth of Candida spp. and of Enterococcus spp. and permits reduced growth of selected coliforms and Proteus spp. Growth of Campylobacter ureolyticus on NAV medium is optimal in anaerobic and enriched hydrogen atmospheres. Additionally, an overnight enrichment step using Bolton broth to which 2 g/L sodium formate, 3 g/L sodium fumarate dibasic and the NAV supplement are added, in place of the commercial Bolton broth supplement, allows improved recovery of C. ureolyticus from patients' faeces.


Assuntos
Anfotericina B , Campylobacter/isolamento & purificação , Meios de Cultura , Fezes/microbiologia , Gastroenterite/microbiologia , Ácido Nalidíxico , Vancomicina , Humanos
16.
Br J Anaesth ; 110(5): 679-89, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23393151

RESUMO

Reduced physical fitness is associated with increased risk of complications after intra-cavity surgery. Aerobic exercise training interventions improve physical fitness in clinical populations. However, it is unclear whether implementing a preoperative aerobic exercise training intervention improves outcome after intra-cavity surgery. We conducted a systematic review (Embase and PubMed, to April 2011) to address the question: does preoperative aerobic exercise training in intra-cavity surgery result in improved postoperative clinical outcomes? Secondary objectives were to describe the effect of such an intervention on physical fitness and health-related quality of life (HRQL) and report feasibility, safety, and cost-effectiveness. Ten studies were identified from 2443 candidate abstracts. Eight studies were small (<100 patients) and all were single centre. Seven studies reported clinical outcomes. Two studies were controlled trials and two used a sham intervention group. One study in cardiac surgery demonstrated reduced postoperative hospital and intensive care length of stay in the intervention group. Eight studies showed improvement in ≥ 1 measure of physical fitness after the intervention. HRQL was reported in five studies; three showed improved HRQL after the intervention. The frequency, duration, and intensities of the exercise interventions varied across the studies. Adherence to exercise interventions was good. Two exercise-related adverse events (transient hypotension) were reported. Evidence for improved postoperative clinical outcome after preoperative aerobic exercise training interventions is limited. However, preoperative aerobic exercise training seems to be generally effective in improving physical fitness in patients awaiting intra-cavity surgery and appears to be feasible and safe.


Assuntos
Exercício Físico , Procedimentos Cirúrgicos Operatórios/reabilitação , Estudos de Viabilidade , Humanos , Aptidão Física , Cuidados Pré-Operatórios/métodos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Ir J Med Sci ; 182(2): 287-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23188546

RESUMO

BACKGROUND: Women younger than 30 years with a focal breast finding have a low incidence of malignancy. Targeted ultrasound is an accurate primary imaging test. MATERIALS AND METHODS: All breast ultrasounds performed from July 1, 2011 to September 30, 2011 were reviewed. All ultrasounds in patients under 25 years were reviewed with regard to indication, imaging findings, and pathology results. RESULTS: Over a 3-month period, 855 breast ultrasounds were performed; 4.1 % breast ultrasounds were performed in a patient under 25 years. Twenty patients had imaging features consistent with a fibroadenoma. Pathology confirmed the diagnosis of fibroadenomas in 15 of the patients. Five patients did not have biopsies performed due to young age or presence of bilateral fibroadenoma. CONCLUSION: A breast nodule in a patient under the age of 25 years with benign clinical findings and imaging features consistent with a fibroadenoma does not require biopsy.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Fibroadenoma/diagnóstico por imagem , Ultrassonografia Mamária , Biópsia , Mama/patologia , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/patologia , Feminino , Humanos , Adulto Jovem
19.
Br J Anaesth ; 109(4): 566-71, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22810563

RESUMO

BACKGROUND: For several types of non-cardiac surgery, the cardiopulmonary exercise testing (CPET)-derived variables anaerobic threshold (AT), peak oxygen consumption (VO2 peak), and ventilatory equivalent for CO(2) (VE/VCO2 ) are predictive of increased postoperative risk: less physically fit patients having a greater risk of adverse outcome. We investigated this relationship in patients undergoing gastric bypass surgery. METHODS: All patients (<190 kg) who were referred for CPET and underwent elective gastric bypass surgery at the Whittington Hospital NHS Trust between September 1, 2009, and February 25, 2011, were included in the study (n=121). Fifteen patients did not complete CPET. CPET variables (VO2 peak, AT, and VE/VCO2 ) were derived for 106 patients. The primary outcome variables were day 5 morbidity and hospital length of stay (LOS). The independent t-test and Fisher's exact test were used to test for differences between surgical outcome groups. The predictive capacity of CPET markers was determined using receiver operating characteristic (ROC) curves. RESULTS: The AT was lower in patients with postoperative complications than in those without [9.9 (1.5) vs 11.1 (1.7) ml kg(-1) min(-1), P=0.049] and in patients with a LOS>3 days compared with LOS ≤ 3 days [10.4 (1.4) vs 11.3 (1.8) ml kg(-1) min(-1), P=0.023]. ROC curve analysis identified AT as a significant predictor of LOS>3 days (AUC 0.640, P=0.030). The VO2 peak and VE/VCO2 were not associated with postoperative outcome. CONCLUSIONS: AT, determined using CPET, predicts LOS after gastric bypass surgery.


Assuntos
Teste de Esforço/métodos , Derivação Gástrica , Adulto , Limiar Anaeróbio/fisiologia , Área Sob a Curva , Peso Corporal/fisiologia , Feminino , Humanos , Tempo de Internação , Masculino , Readmissão do Paciente , Aptidão Física , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Resultado do Tratamento
20.
Int J Colorectal Dis ; 27(11): 1485-91, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22842663

RESUMO

BACKGROUND AND AIMS: Aerobic exercise capacity appears impaired in children with inflammatory bowel disease (IBD). Whether this holds true in adults with IBD is not known. Using cardiopulmonary exercise testing (CPET), we assessed anaerobic threshold (AT) in such patients comparing data with reference values and other elective surgical patients. We also sought to confirm whether the presence of a fistula further reduced AT. METHODS: CPET was performed between November 2007 and December 2010 on patients awaiting abdominopelvic surgery. Gender-specific normal reference values were used for comparison. Unadjusted comparison between two groups was made using Mann-Whitney U test and by unpaired t test. Data were adjusted by analysis of covariance, using age and sex as covariates. Differences between patients' observed values and reference values were tested using paired t tests. RESULTS: Four hundred and fourteen patients (234 male) were studied (mean ± SD age, 56.6 ± 16.4 years; weight, 74.2 ± 15.6 kg). Adjusted AT values in Crohn's disease (CD) were lower than colorectal cancer (11.4 ± 3.4 vs 13.2 ± 3.5 ml.kg(-1).min(-1), p = 0.03) and for all other colorectal disease groups combined (12.6 ± 3.5 ml.kg(-1).min(-1), p = 0.03). AT of Ulcerative colitis (UC) and CD patients together were reduced compared to population reference values (p < 0.05). CONCLUSION: After adjusting for age and sex, CD patients had a reduced AT compared to patients with colorectal cancer and other colorectal disease groups combined. The pathogenesis of this low AT remains to be defined and warrants further investigation.


Assuntos
Teste de Esforço , Tolerância ao Exercício/fisiologia , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/cirurgia , Cuidados Pré-Operatórios , Adulto , Limiar Anaeróbio/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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