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1.
Therap Adv Gastroenterol ; 13: 1756284820937089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33281933

RESUMO

Background and aims: Biologic therapy has emerged as an effective modality amongst the medical treatment options available for ulcerative colitis (UC). However, its impact on post-operative care in patients with UC is still debatable. This review evaluates the risk of post-operative complications following biologic treatment in patients with UC. Methods: A systematic search of the relevant databases was conducted with the aim of identifying studies that compared the post-operative complication rates of UC patients who were either exposed or not exposed to a biologic therapy prior to their surgery. Outcomes of interest included both infection-related complications and overall surgical morbidity. Pooled odds-ratio (OR) and 95% confidence intervals (CI) were calculated using Review Manager 5.3. Results: In all, 20 studies, reviewing a total of 12,494 patients with UC, were included in the meta-analysis. Of these, 2254 patients were exposed to a biologic therapy prior to surgery. The pooled ORs for infection-related complications (n = 8067) and overall complications (n = 11,869) were 0.98 (95% CI 0.66-1.45) and 1.14 (95% CI 1.04-1.28), respectively, which suggested that there was no significant association between the use of pre-operative biologic therapy and post-operative complications. Interestingly, the interval between the last dose of biologic therapy and surgery did not influence the risk of having a post-operative infection. Conclusions: This meta-analysis suggests that pre-operative biologic therapy does not increase the overall risk of having post-operative infection-related or other complications. PROSPERO registration id-CRD42019141827.

2.
J Clin Sleep Med ; 16(1): 41-48, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31957650

RESUMO

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is commonly treated with adenotonsillectomy (AT), bringing risk of perioperative respiratory adverse events (PRAEs). We aimed to concurrently identify clinical and polysomnographic predictors of PRAEs in children undergoing AT. METHODS: Retrospective study of children undergoing AT at a tertiary-care pediatric hospital, with prior in-hospital polysomnography, January 2010 to December 2016. PRAEs included those requiring oxygen, jaw thrust, positive airway pressure, or mechanical ventilation. Relationships of PRAEs to preoperative comorbidities or polysomnography results were examined with univariable logistic regression. Variables with P < .1 and age were included in backward stepwise multivariable logistic regression. Predictive performance (area under the curve, AUC) was validated with bootstrap resampling. RESULTS: Analysis included 374 children, median age 6.1 years; 286 (76.5%) had ≥ 1 comorbidity. 344 (92.0%) had sleep-disordered breathing; 232 (62.0%) moderate-severe; 66 (17.6%) had ≥ 1 PRAE. PRAEs were more frequent in children with craniofacial, genetic, cardiac, airway anomaly, or neurological conditions, AHI ≥ 5 events/h and oxygen saturation nadir ≤ 80% on preoperative polysomnography. Prediction modeling identified cardiac comorbidity (odds ratio [OR] 2.09 [1.11, 3.89]), airway anomaly (OR 3.19 [1.33, 7.49]), and younger age (OR < 3 years: 4.10 (1.79, 9.26; 3 to 6 years: 2.21 [1.18, 4.15]) were associated with PRAEs (AUC 0.74; corrected AUC 0.68). CONCLUSIONS: Prediction modeling concurrently evaluating comorbidities and polysomnography metrics identified cardiac disease, airway anomaly, and young age as independent predictors of PRAEs. These findings suggest that medical comorbidity and age are more important factors in predicting PRAEs than PSG metrics in a medically complex population.

3.
J Gastrointest Oncol ; 10(3): 429-436, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31183192

RESUMO

Background: Field cancerisation proposes that there are pre-malignant genetic mutations in the macroscopically normal mucosal tissue around colorectal cancer. This study aims to evaluate fibroblast growth factor 7 (FGF7) tissue expression in the mucosal field around colorectal cancer. Methods: Gene and protein expression of FGF7, its receptor, FGFR2 and its downstream targets; FRS2α, Erk 1/2 and Akt was measured from mucosal samples in 34 control subjects and 17 cancer patients. Serial samples from tumour, adjacent to tumour and at the resection margin were utilised. Results: FGF7 gene expression was significantly higher in tumour (2.3-fold), adjacent mucosa (3.2-fold) and resection margin (2.8-fold) of cancer patients compared with control subjects (P<0.01 respectively). However, FGFR2 was down regulated (3.5-fold) in the tumour tissue (P<0.001). Protein expression of FRS2α and Akt was significantly lower in tumour tissue compared with the resection margin in cancer patients (P<0.05 respectively). No differences in protein expression of Erk 1/2 were detected. Conclusions: FGF7 was elevated in the mucosal field of cancer patients supporting its potential as a biomarker of field cancerisation. Changes in FRS2α, Akt and Erk 1/2 expression in the tumour tissue indicate that with malignant transformation, FGF7 loses its ability to regulate cellular differentiation.

4.
PLoS One ; 14(5): e0215221, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31120888

RESUMO

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and the British Journal of Anaesthesia (2008-2009, 2014-2016) were identified. Data was extracted independently and in duplicate. Reporting completeness was assessed using the National Institutes of Health Principles and Guidelines for Reporting Preclinical Research. Risk ratios were used for comparative analyses. Of 7615 screened articles, 604 met our inclusion criteria and included experiments reporting on 52 490 animals. The most common topic of investigation was pain and analgesia (30%), rodents were most frequently used (77%), and studies were most commonly conducted in the United States (36%). Use of preclinical reporting guidelines was listed in 10% of applicable articles. A minority of studies fully reported on replicates (0.3%), randomization (10%), blinding (12%), sample-size estimation (3%), and inclusion/exclusion criteria (5%). Statistics were well reported (81%). Comparative analysis demonstrated few differences in reporting rigor between journals, including those that endorsed reporting guidelines. Principal items of study design were infrequently reported, with few differences between journals. Methods to improve implementation and adherence to community-based reporting guidelines may be necessary to increase transparent and consistent reporting in the preclinical anesthesiology literature.


Assuntos
Avaliação Pré-Clínica de Medicamentos/normas , Relatório de Pesquisa/normas , Analgésicos/uso terapêutico , Animais , Bases de Dados Factuais , Guias como Assunto , Dor/tratamento farmacológico
5.
Clin Transl Radiat Oncol ; 15: 83-92, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30775563

RESUMO

Introduction: Target delineation variability is a significant technical impediment in multi-institutional trials which employ intensity modulated radiotherapy (IMRT), as there is a real potential for clinically meaningful variances that can impact the outcomes in clinical trials. The goal of this study is to determine the variability of target delineation among participants from different institutions as part of Southwest Oncology Group (SWOG) Radiotherapy Committee's multi-institutional in-silico quality assurance study in patients with Pancoast tumors as a "dry run" for trial implementation. Methods: CT simulation scans were acquired from four patients with Pancoast tumor. Two patients had simulation 4D-CT and FDG-FDG PET-CT while two patients had 3D-CT and FDG-FDG PET-CT. Seventeen SWOG-affiliated physicians independently delineated target volumes defined as gross primary and nodal tumor volumes (GTV_P & GTV_N), clinical target volume (CTV), and planning target volume (PTV).Six board-certified thoracic radiation oncologists were designated as the 'Experts' for this study. Their delineations were used to create a simultaneous truth and performance level estimation (STAPLE) contours using ADMIRE software (Elekta AB, Sweden 2017). Individual participants' contours were then compared with Experts' STAPLE contours. Results: When compared to the Experts' STAPLE, GTV_P had the best agreement among all participants, while GTV_N showed the lowest agreement among all participants. There were no statistically significant differences in all studied parameters for all TVs for cases with 4D-CT versus cases with 3D-CT simulation scans. Conclusions: High degree of inter-observer variation was noted for all target volume except for GTV_P, unveiling potentials for protocol modification for subsequent clinically meaningful improvement in target definition. Various similarity indices exist that can be used to guide multi-institutional radiotherapy delineation QA credentialing.

6.
Australas Phys Eng Sci Med ; 41(4): 837-845, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30144019

RESUMO

The purpose of the study is to evaluate the accuracy of two deformable image registration algorithms by examining their influence on the dose summation results obtained using 4DCT (four dimensional computed tomography) dose distributions based on '4D' planned and '4D optimal' IMRT (intensity modulated radiation therapy) plans. For ten lung cancer patients, 4D step and shoot IMRT plans were produced. The breathing cycle was divided into ten parts and for each part a set of CT images was acquired. For each patient the treatment plan was copied to the CTs of each phase and subsequently recalculated. Each phase CT was then registered to the average intensity projection (AIP) CT using a deformable image registration (DIR) algorithm and the composite dose distribution was then calculated by summing up the deformed dose distributions from all the phases ('4D' treatment plan). The '4D optimal' treatment plan was created by producing an optimal plan on the CTs of each phase of the respiratory cycle and summing up the deformed dose distributions from all the phases. The results indicate that it is possible to map the dose distributions of different breathing phases in lung using DIR, and that different DIR methods and target characteristics (motion amplitude, size, location) affect the differences between original plan, '4D' and '4D optimal' dose distributions. Although the '4D optimal' plans were designed to achieve 95% target coverage, both of the used DIR methods failed to translate that coverage in some instances. The same variation between these methods was also observed in the '4D' plan comparison. This study shows that it is feasible to perform an acceptably accurate calculation of the composite deformed dose. However, it is important to account for tumor motion and body deformation especially when the tumor volume is small and/or located in the lower lobe of the lung.


Assuntos
Tomografia Computadorizada Quadridimensional/métodos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Humanos , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Radioterapia de Intensidade Modulada , Respiração
7.
Eur J Trauma Emerg Surg ; 44(3): 369-376, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29302699

RESUMO

INTRODUCTION: Hollow viscus injury (HVI) due to blunt abdominal trauma remains a diagnostic challenge, often presenting late and results in delayed intervention. Despite several treatment algorithms, there is currently no consensus on how to manage patients with HVI. The aim of this review was to define clinical outcomes and the effect of delayed intervention in patients with HVI due to blunt abdominal trauma. The primary outcome of interest was difference in mortality between groups. METHODS: Based on the preferred reporting items for systematic reviews and meta-analyses statement, a literature search was performed. Studies comparing clinical outcomes in adult patients with hollow viscus injury due to blunt abdominal trauma undergoing early or delayed laparotomy were included. Two independent reviewers screened the abstracts. RESULTS: In all, 2288 articles were retrieved. After screening, 11 studies were included. Outcomes in 3812 patients were reported. Overall mortality was 17%. Ten studies reported no difference in mortality between groups. A statistical increase in morbidity was described in five studies, and a trend to increased morbidity was seen in a further two studies. Two studies reported increased mortality in delayed intervention in isolated bowel injury. CONCLUSIONS: This systematic review summarises the results of studies considering outcomes in patients with HVI due to blunt abdominal trauma who have early vs delayed intervention. Overall mortality was significant at 17%. If all patients with hollow viscus injury are considered, the majority of studies do not show an increase in mortality. As patients with isolated bowel injuries have higher mortality in the studies reviewed, to improve outcomes in this subset further investigation is warranted.


Assuntos
Traumatismos Abdominais/mortalidade , Traumatismos Abdominais/cirurgia , Tempo para o Tratamento , Vísceras/lesões , Ferimentos não Penetrantes/mortalidade , Ferimentos não Penetrantes/cirurgia , Algoritmos , Humanos , Escala de Gravidade do Ferimento , Laparotomia , Fatores de Risco
8.
Am J Clin Oncol ; 41(9): 905-908, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28537991

RESUMO

BACKGROUND: Urethral cancer is a rare malignancy, representing <1% of all malignancies. Optimal management, due to its rarity, presents as a treatment dilemma for physicians. There is a lack of consensus regarding treatment as large randomized trials cannot be performed; thus, optimal management decisions rely on study of retrospective cases. This is a review of our institutional experience with urethral cancer treated with various treatment modalities. METHODS: A retrospective chart review was performed on 31 patients treated for primary cancer of the urethra from 1958 to 2008. The patients were stratified by sex, histologic type, stage, date of diagnosis, type of treatment, and last follow-up. Early stage cases were designated as Tis-T2N0M0 and advanced cases were designated as T3-4, N+ or M+. Analysis was performed based on clinical stage, treatment modalities and outcomes. RESULTS: Fourteen early stage cases and 17 advanced stage cases of urethral cancer were analyzed. The majority of early stage cases occurred in men (M:F=8:6) and the majority of advanced stage cases occurred in women (M:F=5:12). The most common histology was squamous cell carcinoma for both early and advanced stage cases. Surgery was the preferred modality of treatment for early stage cases (surgery used in 13 cases vs. chemo/radiotherapy used in 1 case) while for advanced cases, radiation ±chemotherapy was commonly used. Overall survival for this series was 45% at mean follow-up of 7 years. Eight of the 14 cases of early stage cancer remained disease free at last follow-up. Comparatively, only 5 of 17 with advanced cancers had no apparent disease at last follow-up. All but one of those patients were treated with combined modality therapy. CONCLUSIONS: Patients with early stage urethral cancers do well with single modality therapy, whereas patients who present with advanced cancers may benefit from combined modality therapy. More extensive study is required to recommend a particular treatment protocol. However, in this rare malignancy, institutional experiences provide the best evidence currently due to the lack of multi-institutional trials.


Assuntos
Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma/mortalidade , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células de Transição/mortalidade , Neoplasias Uretrais/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Uretrais/patologia , Neoplasias Uretrais/terapia
9.
PLoS One ; 12(12): e0190071, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29287123

RESUMO

BACKGROUND: Frailty is an important prognostic factor for adverse outcomes and increased resource use in the growing population of older surgical patients. We identified and appraised studies that tested interventions in populations of frail surgical patients to improve perioperative outcomes. METHODS: We systematically searched Cochrane, CINAHL, EMBASE and Medline to identify studies that tested interventions in populations of frail patients having surgery. All phases of study selection, data extraction, and risk of bias assessment were done in duplicate. Results were synthesized qualitatively per a prespecified protocol (CRD42016039909). RESULTS: We identified 2 593 titles; 11 were included for final analysis, representing 1 668 participants in orthopedic, general, cardiac, and mixed surgical populations. Only one study was multicenter and risk of bias was moderate to high in all studies. Interventions were applied pre- and postoperatively, and included exercise therapy (n = 4), multicomponent geriatric care protocols (n = 5), and blood transfusion triggers (n = 1); no specific surgical techniques were compared. Exercise therapy, applied pre-, or post-operatively, was associated with significant improvements in functional outcomes and improved quality of life. Multicomponent protocols suffered from poor compliance and difficulties in implementation. Transfusion triggers had no significant impact on mortality or other outcomes. CONCLUSIONS: Despite a growing literature that demonstrates strong independent associations between frailty and adverse outcomes, few interventions have been tested to improve the outcomes of frail surgical patients, and most available studies are at substantial risk of bias. Multicenter, low risk of bias, studies of perioperative exercise are needed, while substantial efforts are required to develop and test other interventions to improve the outcomes of frail people having surgery.


Assuntos
Idoso Fragilizado , Procedimentos Cirúrgicos Operatórios/normas , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Terapia por Exercício , Feminino , Humanos , Masculino , Qualidade de Vida , Resultado do Tratamento
10.
Int J Colorectal Dis ; 32(11): 1609-1616, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28828520

RESUMO

PURPOSE: Adenoma detection in colorectal cancer survivors is poorly characterised with insufficient evidence to inform frequency of surveillance schedule. The aim of this study was to examine adenoma incidence and recurrence in patients who have undergone colorectal cancer resection with curative intent. Survival outcomes were compared to determine if the presence of adenomas could be used to identify patients at higher risk of local recurrence. METHODS: This is a retrospective observational cohort study at a single tertiary institution between 2006 and 2012. Five hundred fifteen consecutive patients with stage I-III colorectal cancer who had preoperative colonoscopy and curative surgery were included (median follow-up 56 months (36-75 months). RESULTS: In total, 352/515 (68%) patients underwent postoperative surveillance colonoscopy in the first 5 years after resection. Male gender was associated with greater risk of detecting synchronous adenoma at index colonoscopy or in the resection specimen (OR 2.35, p < 0.001). In the first 5 years after cancer surgery, synchronous adenoma, male gender and right sided primary tumour were independent predictors of metachronous lesions (OR 2.13, p = 0.009; OR 2.07, p = 0.027 and OR 2.34, p = 0.004, respectively). Presence of synchronous or metachronous adenoma had no impact upon incidence of local recurrence, overall or disease free survival. CONCLUSIONS: Patients with synchronous adenoma remain at high risk of adenoma recurrence despite undergoing colonic resection and should be considered for early endoscopic surveillance. Men and those undergoing right-sided resection have a higher risk of metachronous adenoma in the long term and may benefit from more frequent endoscopic surveillance post resection.


Assuntos
Adenoma , Colectomia , Colonoscopia , Neoplasias Colorretais , Recidiva Local de Neoplasia , Neoplasias Primárias Múltiplas , Segunda Neoplasia Primária , Adenoma/epidemiologia , Adenoma/patologia , Colectomia/efeitos adversos , Colectomia/métodos , Colonoscopia/métodos , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/epidemiologia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/patologia , Planejamento de Assistência ao Paciente , Medição de Risco/métodos , Fatores de Risco , Fatores Sexuais , Reino Unido/epidemiologia
11.
Med Educ ; 51(9): 953-962, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28833426

RESUMO

OBJECTIVES: Although trainees and trainers find feedback interactions beneficial, difficulties in giving and receiving feedback are reported. Few studies have explored what drives trainees to seek feedback. This study explores how workplace-based assessments (WBAs) influence the ways surgical trainees seek feedback and feedback interactions. METHODS: Utilising a template analysis approach, we conducted 10 focus groups with 42 surgical trainees from four regions across the UK. Data were independently coded by three researchers, incorporating three a priori themes identified from a previous quantitative study. Further themes emerged from exploration of these data. The final template, agreed by the three researchers, was applied to all focus group transcripts. The themes were linked in a diagrammatical form to allow critical exploration of the data. RESULTS: Trainees' perceptions of the purpose of WBA for learning or an assessment of learning, and their relationship with their trainer impacted upon how trainees chose to use WBA. Perceiving WBA as a test led trainees to 'play the game': seek positive and avoid negative feedback through WBA. Perceiving WBA as a chance to learn led trainees to seek negative feedback. Some trainees sought negative feedback outside WBA. Negative feedback was more important for changing practice compared with positive feedback, which enabled trainees to 'look good' but had less of an effect on changing clinical practice. The timing of feedback relative to WBA was also important, with immediate feedback being more beneficial for learning; however, delayed feedback was still sought using WBA. DISCUSSION: Trainees' perceptions of the purpose of WBA and their relationship with their trainer informed when they chose to seek feedback. Trainees who perceived WBA as a test were led to 'play the game' by seeking positive and avoiding negative feedback. Outside of WBA, trainees sought negative feedback, which was most important for change in practice.


Assuntos
Competência Clínica/normas , Avaliação Educacional/métodos , Feedback Formativo , Cirurgia Geral/educação , Internato e Residência/métodos , Local de Trabalho/normas , Humanos , Internato e Residência/normas , Aprendizagem , Percepção
12.
Acad Med ; 92(6): 827-834, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28557949

RESUMO

PURPOSE: To investigate surgical trainee feedback-seeking behaviors-directly asking for feedback (inquiry) and observing and responding to situational clues (monitoring)-in the context of workplace-based assessment (WBA). METHOD: A hypothetical model of trainee feedback-seeking behavior was developed using existing literature. A questionnaire, incorporating previously validated instruments from organizational psychology, was distributed to general surgical trainees at 23 U.K. hospitals in 2012-2013. Statistical modeling techniques compared the data with 12 predetermined hypothetical relationships between feedback-seeking behaviors and predictive variables (goal orientation, supervisory style) through mediating variables (perceptions of personal benefits and costs of feedback) to develop a final model. RESULTS: Of 235 trainees invited, 178 (76%) responded. Trainees completed 48 WBAs/year on average, and 73% reported receiving feedback via WBA. The final model was of good fit (chi-square/degree of freedom ratio = 1.620, comparative fit index = 0.953, root mean square error of approximation = 0.059). Modeled data showed trainees who perceive personal benefits to feedback use both feedback inquiry and monitoring to engage in feedback interactions. Trainees who seek feedback engage in using WBA. Trainees' goal orientations and perceptions of trainers' supervisory styles as supportive and instrumental are associated with perceived benefits and costs to feedback. CONCLUSIONS: Trainees actively engage in seeking feedback and using WBA. Their perceptions of feedback benefits and costs and supervisory style play a role in their feedback-seeking behavior. Encouraging trainees to actively seek feedback by providing specific training and creating a supportive environment for feedback interactions could positively affect their ability to seek feedback.


Assuntos
Competência Clínica/normas , Avaliação Educacional/métodos , Feedback Formativo , Cirurgia Geral/educação , Internato e Residência/normas , Apoio ao Desenvolvimento de Recursos Humanos/normas , Local de Trabalho/normas , Adulto , Feminino , Humanos , Masculino , Inquéritos e Questionários , Reino Unido , Adulto Jovem
13.
J Racial Ethn Health Disparities ; 4(2): 165-168, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-26969160

RESUMO

OBJECTIVES: Despite an overall improvement in cervical cancer screening, incidence, and mortality rates for minorities in the USA, regional differences in screening and stage at presentation have been observed. This study evaluated cervical cancer disparities in a predominately Hispanic population treated in a major treatment center in San Antonio, Texas. METHODS AND MATERIALS: Data on 446 patients with cervical cancer treated between 2000 and 2011 at the Cancer Therapy and Research Center in San Antonio, Texas, were reviewed. Sufficient information was obtained on 319 patients and was compared with the Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: Of 319 patients treated for cervical cancer between 2000 and 2011, 209 were Hispanics and 110 were Whites (82), Blacks (20), Asians (7), and others (1). The median and mean ages at diagnosis were 47 and 49, respectively. Only 36 % were known to have screening Pap tests prior to diagnosis, of which only 24 had yearly Pap tests. Forty-two patients (20 %) of those with no known screening Pap tests presented with stage IV disease at diagnosis (vs. 3 % of those with known Pap tests). Among the Hispanics, 68 % presented with regional disease (vs. 37 % SEER) and 46 % were stage III or higher disease, with stage IIIB accounting for 30 % of total. Although the overall age-adjusted death rates were higher in Hispanics due to a higher percentage of more advanced disease, survival rates appear similar, stage for stage, to the SEER data. CONCLUSION: Even in a major city, Hispanics often present with more advanced cervical cancer than the general population. In order to minimize the cervical cancer disparities, efforts and strategies are needed to study the cultural and locale effects and to implement preventive measures and adaptive health education.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Hispano-Americanos/estatística & dados numéricos , Neoplasias do Colo do Útero/etnologia , Afro-Americanos/estatística & dados numéricos , Americanos Asiáticos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Teste de Papanicolaou/estatística & dados numéricos , Estudos Retrospectivos , Programa de SEER , Texas , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/estatística & dados numéricos
14.
J Med Imaging Radiat Sci ; 47(1): 30-42.e1, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31047161

RESUMO

The purpose of the study was to assess internal target volume changes through the breathing cycle and associated tumour motion for lung patients and to establish possible correlations between different parameters. Respiration-induced volume changes with breathing cycle and the associated tumour motion were analyzed for 11 patients. Selected phases were the maximum and average intensity projections and the 10 phases of equal duration and separation obtained through the respiratory cycle. Tumour centre of mass (COM) motion planes were generated using least square fitting, and their angles and orientations were then compared between the cases studied. Trajectories that are composed by the points of COM location in different phases were identified, and their interrelation was assessed through different similarity measures. The results were used to determine if there is any correlation between parameters chosen and if the margins conventionally used for the planning target volume creation successfully encompassed lung tumour motion and volume change. The results show that the extent of tumour motion was related to its volume and location. The tumour displacement was predominantly left and inferior. Planar fitting to COM motion data through respiratory phases demonstrated some correlation in best fit motion plane positions between different data sets. In the plane fit comparison, for each patient, the lower root mean square error values showed that a good planar fit can be achieved for the COM motion path. The evaluation of the inhale and exhale trajectories may allow, for certain tumour locations and size, contouring on only inhalation or exhalation phases, knowing that tumour motion will be adequately covered on the other phases. Taking all the data into account and knowing the tumour size and location, a good estimate can be made of the motion plane position in the three-dimensional space and the required dosimetric margins.

15.
Dis Colon Rectum ; 58(10): 999-1013, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26347973

RESUMO

BACKGROUND: Antegrade continence enema is a proximal colonic stoma that allows antegrade lavage of the colon for the treatment of fecal incontinence and functional constipation. Its role in the treatment of these conditions in adults has not been established. OBJECTIVE: This review aimed to evaluate the clinical response and complications of antegrade continence enema in the adult population. DATA SOURCES: A systematic literature search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases from January 1980 to October 2013 was conducted. STUDY SELECTION: Studies reporting clinical outcomes of antegrade continence enema in adult patients were considered. Only studies with participants aged 16 years and older were selected. INTERVENTION(S): Use of the antegrade continence enema for the treatment of constipation and incontinence in adults was investigated. MAIN OUTCOME MEASURES: The primary outcome was the number of patients irrigating their stoma. Secondary outcomes included the incidence of stoma stenosis, assessment of functional outcome, and evaluation of quality of life. RESULTS: Overall, 15 studies were selected, describing outcomes in 374 patients. All of the reports were observational cross-sectional studies, and 4 were prospective. The number of participants still using their stoma ranged from 47% to 100% over a follow-up period of 6 to 55 months. Eleven studies reported achievement of full continence in 33% to 100% of patients. Four studies described functional outcomes, and 7 studies reported a wide range of patient satisfaction. The rate of stoma stenosis varied from 8% to 50%. LIMITATIONS: There were considerable heterogeneities within and across studies. Most studies were of poor quality, as reflected in the Methodological Index for Nonrandomized Studies score. CONCLUSIONS: Antegrade continence enema has been reported as an acceptable treatment of both functional constipation and fecal incontinence in adults across several analyses. There is wide variation regarding outcome measures. Larger prospective studies are required to assess the role of antegrade continence enema in the adult population.


Assuntos
Colostomia , Constipação Intestinal , Enema/métodos , Incontinência Fecal , Complicações Pós-Operatórias , Qualidade de Vida , Irrigação Terapêutica/métodos , Adulto , Colostomia/efeitos adversos , Colostomia/métodos , Colostomia/psicologia , Constipação Intestinal/fisiopatologia , Constipação Intestinal/psicologia , Constipação Intestinal/terapia , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Incontinência Fecal/fisiopatologia , Incontinência Fecal/psicologia , Incontinência Fecal/terapia , Humanos , Incidência , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/psicologia
16.
Cell Rep ; 12(8): 1272-88, 2015 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-26279567

RESUMO

The pacemaker properties of the suprachiasmatic nucleus (SCN) circadian clock are shaped by mechanisms that influence the expression and behavior of clock proteins. Here, we reveal that G-protein-coupled receptor kinase 2 (GRK2) modulates the period, amplitude, and entrainment characteristics of the SCN. Grk2-deficient mice show phase-dependent alterations in light-induced entrainment, slower recovery from jetlag, and longer behavioral rhythms. Grk2 ablation perturbs intrinsic rhythmic properties of the SCN, increasing amplitude and decreasing period. At the cellular level, GRK2 suppresses the transcription of the mPeriod1 gene and the trafficking of PERIOD1 and PERIOD2 proteins to the nucleus. Moreover, GRK2 can physically interact with PERIOD1/2 and promote PERIOD2 phosphorylation at Ser545, effects that may underlie its ability to regulate PERIOD1/2 trafficking. Together, our findings identify GRK2 as an important modulator of circadian clock speed, amplitude, and entrainment by controlling PERIOD at the transcriptional and post-translational levels.


Assuntos
Núcleo Celular/metabolismo , Relógios Circadianos/genética , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Proteínas Circadianas Period/metabolismo , Processamento de Proteína Pós-Traducional , Transporte Ativo do Núcleo Celular , Animais , Linhagem Celular , Células Cultivadas , Quinase 2 de Receptor Acoplado a Proteína G/genética , Masculino , Camundongos , Proteínas Circadianas Period/genética , Fosforilação , Ligação Proteica
17.
World J Gastroenterol ; 21(13): 3763-72, 2015 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-25852261

RESUMO

Despite considerable advances in our understanding of cancer biology, early diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma sequence, cancer develops through the progressive accumulation of mutations in key genes that regulate cell growth. However, recent mathematical modelling suggests that some of these genetic events occur prior to the development of any discernible histological abnormality. Cells acquire pro-tumourigenic mutations that are not able to produce morphological change but predispose to cancer formation. These cells can grow to form large patches of mucosa from which a cancer arises. This process has been termed "field cancerisation". It has received little attention in the scientific literature until recently. Several studies have now demonstrated cellular, genetic and epigenetic alterations in the macroscopically normal mucosa of colorectal cancer patients. In some reports, these changes were effectively utilised to identify patients with a neoplastic lesion suggesting potential application in the clinical setting. In this article, we present the scientific evidence to support field cancerisation in colorectal cancer and discuss important limitations that require further investigation. Characterisation of the field defect is necessary to enable early diagnosis of colorectal cancer and identify molecular targets for chemoprevention. Field cancerisation offers a promising prospect for experimental cancer research and has potential to improve patient outcomes in the clinical setting.


Assuntos
Biomarcadores Tumorais/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Colo/patologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Mucosa Intestinal/patologia , Animais , Detecção Precoce de Câncer/métodos , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Testes Genéticos , Humanos , Modelos Genéticos , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Fatores de Risco
18.
Dis Colon Rectum ; 58(4): 406-14, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25751797

RESUMO

BACKGROUND: The detection of lymph node involvement is fundamental to the staging of rectal cancer, and aids in prognostication and identification of patients who will benefit from adjuvant therapy. The anatomical variation in distribution and size of mesorectal lymph nodes has received scant attention. OBJECTIVE: This study aimed to determine the size and distribution of lymph nodes in rectal cancer resection specimens. DESIGN: This was a prospective, observational study of rectal cancer resection specimens analyzed by a single histopathologist. SETTING: This study was conducted from January 2007 to July 2013 at the authors' institution. PATIENTS: Two hundred forty-four consecutive patients underwent resection for rectal cancer. MAIN OUTCOME MEASURES: The size and distribution of lymph nodes in the resection specimens and the anatomical position of mesorectal lymph nodes in relation to the peritoneal reflection, tumor, and anal verge were recorded. RESULTS: A total of 10,473 lymph nodes were retrieved in 244 patients (75 women; median age, 68 years (interquartile range, 59-75 years)). One hundred seventy-three anterior resection and 71 abdominoperineal resection specimens were analyzed. Median lymph node yield was 41 lymph nodes (interquartile range, 31-52); 344 of 10,473 (3.2%) lymph nodes were positive. Lymph nodes were distributed in the mesorectum, sigmoid mesentery, and vascular pedicle in 40%, 32%, and 28% of the patients. Sixty-eight percent of mesorectal lymph nodes were above the peritoneal reflection. Mesorectal lymph node distribution in relation to the tumor was 53% above, 36% adjacent to, and only 11% below the tumor. Ninety-five of 334 (28%) positive nodes were ≤3 mm in diameter. LIMITATIONS: Resection specimens analyzed by other pathologists (<5%) have not been included, and fat clearance techniques were not used to retrieve lymph nodes. CONCLUSIONS: To ensure accurate nodal staging of rectal cancer, both resection and subsequent pathological evaluation should focus on the mesorectum in close proximity to the tumor and along the superior rectal artery. Small lymph nodes (<3 mm in size) should not be overlooked, and lymph node metastasis to the sigmoid mesentery is rare (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A177).


Assuntos
Linfonodos/patologia , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Idoso , Biópsia , Feminino , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamanho do Órgão , Estudos Prospectivos
19.
PLoS Genet ; 10(10): e1004695, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25330117

RESUMO

The suprachiasmatic nucleus (SCN) acts as the central clock to coordinate circadian oscillations in mammalian behavior, physiology and gene expression. Despite our knowledge of the circadian transcriptome of the SCN, how it impacts genome-wide protein expression is not well understood. Here, we interrogated the murine SCN proteome across the circadian cycle using SILAC-based quantitative mass spectrometry. Of the 2112 proteins that were accurately quantified, 20% (421 proteins) displayed a time-of-day-dependent expression profile. Within this time-of-day proteome, 11% (48 proteins) were further defined as circadian based on a sinusoidal expression pattern with a ∼24 h period. Nine circadianly expressed proteins exhibited 24 h rhythms at the transcript level, with an average time lag that exceeded 8 h. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated light-to-dark and dark-to-light transitions, and was enriched for proteins involved in several key biological pathways, most notably, mitochondrial oxidative phosphorylation. Additionally, predicted targets of miR-133ab were enriched in specific hierarchical clusters and were inversely correlated with miR133ab expression in the SCN. These insights into the proteomic landscape of the SCN will facilitate a more integrative understanding of cellular control within the SCN clock.


Assuntos
Ritmo Circadiano/fisiologia , Proteoma/metabolismo , Núcleo Supraquiasmático/metabolismo , Animais , Regulação da Expressão Gênica , Luz , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Proteínas Mitocondriais/metabolismo , Fosforilação Oxidativa , Mapas de Interação de Proteínas , Proteoma/análise , Proteômica/instrumentação , Proteômica/métodos , Transcriptoma
20.
Surgeon ; 12(3): 134-40, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24210949

RESUMO

INTRODUCTION: Current guidelines for the management of acute gallstone pancreatitis recommend cholecystectomy as definitive treatment during primary admission or within 2 weeks of discharge, with the aim of preventing recurrent pancreatitis. However, cholecystectomy during the inflammatory phase may increase surgical complication rates. This study aimed to determine whether adherence to the guidelines prevents recurrent pancreatitis while minimising surgical complications. METHODS: Multi-centre review of seven UK hospitals, indentifying patients presenting with their first episode of gallstone pancreatitis between 2006 and 2008. RESULTS: A total of 523 patients with gallstone pancreatitis were identified, of which 363 (69%) underwent cholecystectomy (72 during the primary admission or within 2 weeks of discharge; 291 following this). Overall, 7% of patients had a complication related to cholecystectomy of which a greater proportion occurred when cholecystectomy was performed within guideline parameters (13% vs 6%; p = 0.07). 11% of patients were readmitted with recurrent pancreatitis prior to surgery, with those undergoing cholecystectomy outside guideline parameters being most at risk (p = 0.006). CONCLUSION: This study suggests cholecystectomy within guideline parameters significantly reduces recurrence of pancreatitis but may increase the risk of surgical complications. A prospective randomised study to assess the associated morbidity is required to inform future guidelines.


Assuntos
Colecistectomia/normas , Cálculos Biliares/cirurgia , Fidelidade a Diretrizes , Pancreatite/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica , Feminino , Seguimentos , Cálculos Biliares/complicações , Cálculos Biliares/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pancreatite/diagnóstico , Pancreatite/etiologia , Projetos Piloto , Recidiva , Estudos Retrospectivos
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