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1.
BMJ Open Gastroenterol ; 10(1)2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37399433

RESUMO

OBJECTIVE: Endoscopic ultrasound-guided through-the-needle microbiopsy (EUS-TTNB) forceps is a recent development that facilitates sampling of the walls of pancreatic cystic lesions (PCL) for histological analysis. We aimed to assess the impact of EUS-TTNB and its influence on patient management in a tertiary pancreas centre. DESIGN: A prospective database of consecutive patients who underwent EUS-TTNB from March 2020 to August 2022 at a tertiary referral centre was retrospectively analysed. RESULTS: Thirty-four patients (22 women) were identified. Technical success was achieved in all cases. Adequate specimens for histological diagnosis were obtained in 25 (74%) cases. Overall, EUS-TTNB led to a change in management in 24 (71%) cases. Sixteen (47%) patients were downstaged, with 5 (15%) discharged from surveillance. Eight (24%) were upstaged, with 5 (15%) referred for surgical resection. In the 10 (29%) cases without change in management, 7 (21%) had confirmation of diagnosis with no change in surveillance, and 3 (9%) had insufficient biopsies on EUS-TTNB. Two (6%) patients developed post-procedural pancreatitis, and 1 (3%) developed peri-procedural intracystic bleeding with no subsequent clinical sequelae. CONCLUSION: EUS-TTNB permits histological confirmation of the nature of PCL, which can alter management outcomes. Care should be taken in patient selection and appropriately consented due to the adverse event rate.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Cisto Pancreático , Humanos , Feminino , Estudos Retrospectivos , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Pâncreas/patologia , Endossonografia , Cisto Pancreático/diagnóstico
2.
BMC Microbiol ; 23(1): 52, 2023 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-36858965

RESUMO

It is increasingly being recognised that changes in the gut microbiome have either a causative or associative relationship with colorectal cancer (CRC). However, most of this research has been carried out in a small number of developed countries with high CRC incidence. It is unknown if lower incidence countries such as India have similar microbial associations.Having previously established protocols to facilitate microbiome research in regions with developing research infrastructure, we have now collected and sequenced microbial samples from a larger cohort study of 46 Indian CRC patients and 43 healthy volunteers.When comparing to previous global collections, these samples resemble other Asian samples, with relatively high levels of Prevotella. Predicting cancer status between cohorts shows good concordance. When compared to a previous collection of Indian CRC patients, there was similar concordance, despite different sequencing technologies between cohorts.These results show that there does seem to be a global CRC microbiome, and that some inference between studies is reasonable. However, we also demonstrate that there is definite regional variation, with more similarities between location-matched comparisons. This emphasises the importance of developing protocols and advancing infrastructure to allow as many countries as possible to contribute to microbiome studies of their own populations.


Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Humanos , Povo Asiático , Estudos de Coortes , Neoplasias Colorretais/microbiologia
3.
J Cancer Educ ; 38(2): 440-447, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35076863

RESUMO

Obesity increases risk of cancer onset and promulgates cancer mortality. Healthy Living Partnerships to Prevent Cancer (HELP PC) is an adapted intensive lifestyle intervention that is facilitated by community health workers (CHWs). The primary objective of this one-arm pilot study was to test the feasibility of evaluating HELP PC in a rural community by assessing participant recruitment, retention, and adherence to the intervention. The secondary objectives of this study were to evaluate the feasibility of collecting study measures and analyze intervention effects to inform future studies. Adults of all races and a BMI ≥ 25 kg/m2 who resided in the Dan River Region of Southern Virginia were recruited. Participants received 24 weekly (hour-long) group sessions led by a CHW and two consultations with a registered dietitian (RDN). Seventy-five percent (21/28) of eligible subjects were enrolled (n = 21; mean age = 46 years; 67% African American; 90% female; median BMI = 36.1), and recruitment was completed in 2 weeks. Fifty-two percent (11/21) of participants attended >70% of group sessions (adherence) and 98% of RDN consultations were attended. Eighty-six percent (n=18) of participants completed the 6-month follow-up visit (retention), and showed improvements in moderate physical activity, health literacy, general health, energy, and emotional well-being. Feasibility of HELP PC was established through efficient participant recruitment, modest attendance, high retention, and execution of data collection procedures. Importantly, findings can be applied to advance cancer prevention lifestyle interventions in rural communities.


Assuntos
Neoplasias , População Rural , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Viabilidade , Projetos Piloto , Estilo de Vida , Estilo de Vida Saudável , Neoplasias/prevenção & controle
4.
BMC Cancer ; 22(1): 1144, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344941

RESUMO

BACKGROUND: Lynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the consideration of additional surveillance intervention(s) through the application of non-invasive diagnostic devices has yet to be longitudinally observed in LS patients. In this study, we will examine the role of annual faecal immunochemical testing (FIT) alongside biennial colonoscopy for CRC surveillance in people with LS. METHODS/DESIGN: In this single-arm, prospective, non-randomised study, 400 LS patients will be recruited across 11 National Health Service (NHS) Trusts throughout the United Kingdom. Study inclusion requires a LS diagnosis, between 25 and 73 years old, and a routine surveillance colonoscopy scheduled during the recruitment period. Eligible patients will receive a baseline OC-Sensor™ FIT kit ahead of their colonoscopy, and annually for 3 years thereafter. A pre-paid envelope addressed to the central lab will be included within all patient mailings for the return of FIT kits and relevant study documents. A questionnaire assessing attitudes and perception of FIT will also be included at baseline. All study samples received by the central lab will be assayed on an OC-Sensor™ PLEDIA Analyser. Patients with FIT results of ≥6 µg of Haemoglobin per gram of faeces (f-Hb) at Years 1 and/or 3 will be referred for colonoscopy via an urgent colonoscopy triage pathway. 16S rRNA gene V4 amplicon sequencing will be carried out on residual faecal DNA of eligible archived FIT samples to characterise the faecal microbiome. DISCUSSION: FIT may have clinical utility alongside colonoscopic surveillance in people with LS. We have designed a longitudinal study to examine the efficacy of FIT as a non-invasive modality. Potential limitations of this method will be assessed, including false negative or false positive FIT results related to specific morphological features of LS neoplasia or the presence of post-resection anastomotic inflammation. The potential for additional colonoscopies in a subset of participants may also impact on colonoscopic resources and patient acceptability. TRIAL REGISTRATION: Trial Registration: ISRCTN, ISRCTN15740250 . Registered 13 July 2021.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Estudos Longitudinais , Estudos Prospectivos , Medicina Estatal , RNA Ribossômico 16S , Sangue Oculto , Colonoscopia , Hemoglobinas/análise , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Detecção Precoce de Câncer/métodos
5.
Histopathology ; 79(5): 690-699, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33872400

RESUMO

AIMS: Screening all patients newly diagnosed with colorectal cancer (CRC) for possible Lynch syndrome (LS) has been recommended in the United Kingdom since the National Institute for Health and Care Excellence (NICE) released new diagnostics guidance in February 2017. We sought to validate the NICE screening pathway through a prospective regional programme throughout a 5.2-million population during a 2-year period. METHODS AND RESULTS: Pathology departments at 14 hospital trusts in the Yorkshire and Humber region of the United Kingdom were invited to refer material from patients with newly diagnosed CRC aged 50 years or over between 1 April 2017 and 31 March 2019 for LS screening. Testing consisted of immunohistochemistry for MLH1, PMS2, MSH2 and MSH6 followed by BRAF mutation analysis ± MLH1 promoter methylation testing in cases showing MLH1 loss. A total of 3141 individual specimens were submitted for testing from 12 departments consisting of 3061 unique tumours and 2791 prospectively acquired patients with CRC. Defective mismatch repair (dMMR) was observed in 15% of cases. In cases showing MLH1 loss, 76% contained a detectable BRAF mutation and, of the remainder, 77% showed MLH1 promoter hypermethylation. Of the patients included in the final analysis, 81 (2.9%) had an indication for germline testing. CONCLUSION: LS screening using the NICE diagnostics guidance pathway is deliverable at scale identifying significant numbers of patients with dMMR. This information is used to refer patients to regional clinical genetics services in addition to informing treatment pathways including the use of adjuvant/neoadjuvant chemotherapy and immunotherapy.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Detecção Precoce de Câncer/métodos , Testes Genéticos/métodos , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Metilação de DNA , Reparo de Erro de Pareamento de DNA/genética , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL/genética , Mutação , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Reino Unido
6.
Clin Cancer Res ; 27(8): 2246-2254, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33658300

RESUMO

PURPOSE: There is potential for fecal microbiome profiling to improve colorectal cancer screening. This has been demonstrated by research studies, but it has not been quantified at scale using samples collected and processed routinely by a national screening program. EXPERIMENTAL DESIGN: Between 2016 and 2019, the largest of the NHS Bowel Cancer Screening Programme hubs prospectively collected processed guaiac fecal occult blood test (gFOBT) samples with subsequent colonoscopy outcomes: blood-negative [n = 491 (22%)]; colorectal cancer [n = 430 (19%)]; adenoma [n = 665 (30%)]; colonoscopy-normal [n = 300 (13%)]; nonneoplastic [n = 366 (16%)]. Samples were transported and stored at room temperature. DNA underwent 16S rRNA gene V4 amplicon sequencing. Taxonomic profiling was performed to provide features for classification via random forests (RF). RESULTS: Samples provided 16S amplicon-based microbial profiles, which confirmed previously described colorectal cancer-microbiome associations. Microbiome-based RF models showed potential as a first-tier screen, distinguishing colorectal cancer or neoplasm (colorectal cancer or adenoma) from blood-negative with AUC 0.86 (0.82-0.89) and AUC 0.78 (0.74-0.82), respectively. Microbiome-based models also showed potential as a second-tier screen, distinguishing from among gFOBT blood-positive samples, colorectal cancer or neoplasm from colonoscopy-normal with AUC 0.79 (0.74-0.83) and AUC 0.73 (0.68-0.77), respectively. Models remained robust when restricted to 15 taxa, and performed similarly during external validation with metagenomic datasets. CONCLUSIONS: Microbiome features can be assessed using gFOBT samples collected and processed routinely by a national colorectal cancer screening program to improve accuracy as a first- or second-tier screen. The models required as few as 15 taxa, raising the potential of an inexpensive qPCR test. This could reduce the number of colonoscopies in countries that use fecal occult blood test screening.


Assuntos
Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Microbioma Gastrointestinal , Idoso , Idoso de 80 Anos ou mais , Colonoscopia , Neoplasias Colorretais/microbiologia , DNA Bacteriano/isolamento & purificação , Detecção Precoce de Câncer/estatística & dados numéricos , Inglaterra , Fezes/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Estudos Prospectivos , RNA Ribossômico 16S/genética , Medicina Estatal
7.
Genome Med ; 13(1): 27, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593386

RESUMO

BACKGROUND: The incidence of colorectal cancer (CRC) is increasing in developing countries, yet limited research on the CRC- associated microbiota has been conducted in these areas, in part due to scarce resources, facilities, and the difficulty of fresh or frozen stool storage/transport. Here, we aimed (1) to establish a broad representation of diverse developing countries (Argentina, Chile, India, and Vietnam); (2) to validate a 'resource-light' sample-collection protocol translatable in these settings using guaiac faecal occult blood test (gFOBT) cards stored and, importantly, shipped internationally at room temperature; (3) to perform initial profiling of the collective CRC-associated microbiome of these developing countries; and (4) to compare this quantitatively with established CRC biomarkers from developed countries. METHODS: We assessed the effect of international storage and transport at room temperature by replicating gFOBT from five UK volunteers, storing two in the UK, and sending replicates to institutes in the four countries. Next, to determine the effect of prolonged UK storage, DNA extraction replicates for a subset of samples were performed up to 252 days apart. To profile the CRC-associated microbiome of developing countries, gFOBT were collected from 41 treatment-naïve CRC patients and 40 non-CRC controls from across the four institutes, and V4 16S rRNA gene sequencing was performed. Finally, we constructed a random forest (RF) model that was trained and tested against existing datasets from developed countries. RESULTS: The microbiome was stably assayed when samples were stored/transported at room temperature and after prolonged UK storage. Large-scale microbiome structure was separated by country and continent, with a smaller effect from CRC. Importantly, the RF model performed similarly to models trained using external datasets and identified similar taxa of importance (Parvimonas, Peptostreptococcus, Fusobacterium, Alistipes, and Escherichia). CONCLUSIONS: This study demonstrates that gFOBT, stored and transported at room temperature, represents a suitable method of faecal sample collection for amplicon-based microbiome biomarkers in developing countries and suggests a CRC-faecal microbiome association that is consistent between developed and developing countries.


Assuntos
Neoplasias Colorretais/microbiologia , Países Desenvolvidos , Países em Desenvolvimento , Fezes/microbiologia , Microbioma Gastrointestinal , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Geografia , Guaiaco , Humanos , Masculino , Pessoa de Meia-Idade , Sangue Oculto , Meios de Transporte , Reino Unido
8.
J Robot Surg ; 14(4): 649-653, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31741292

RESUMO

Injury of the inferior vena cava is an infrequent but serious complication of paraaortic lymphadenectomy. Training in the management of this injury might be enhanced through animate simulation. Our objective was to assess a simulated animal model for training in intraoperative management of inferior vena cava injury in the context of robotic paraaortic lymphadenectomy. We used a female domestic pig to create an injury of the inferior vena cava, which was then managed two ways with robotically assisted surgery. Edited videos of the two models were assessed by 32 senior learners and 23 attending faculty. The assessments included key competencies and domains of fidelity. A scale of poor, fair, or good was utilized. The injury and management simulated those seen in humans, both anatomically and surgically, although deficiencies were noted. Specifically, a reduced rapidity of bleeding and a related greater ease of control contributed to lower ratings for some aspects of fidelity. Fidelity and addressing the key competency of suture repair also received some lower ratings, particularly from vascular surgeons and their trainees. The porcine model for simulation of inferior vena cava injury during robotically assisted paraaortic lymphadenectomy may be useful for training purposes.


Assuntos
Educação Médica/métodos , Cuidados Intraoperatórios/métodos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/cirurgia , Excisão de Linfonodo/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/educação , Veia Cava Inferior/lesões , Veia Cava Inferior/cirurgia , Animais , Feminino , Humanos , Modelos Animais , Procedimentos Cirúrgicos Robóticos/métodos , Técnicas de Sutura/educação , Suínos , Gravação em Vídeo
9.
J Trauma Acute Care Surg ; 88(4): 508-514, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31688825

RESUMO

BACKGROUND: Accurate medication reconciliation in trauma patients is essential but difficult. Currently, there is no established clinical method of detecting direct oral anticoagulants (DOACs) in trauma patients. We hypothesized that a liquid chromatography-mass spectrometry (LCMS)-based assay can be used to accurately detect DOACs in trauma patients upon hospital arrival. METHODS: Plasma samples were collected from 356 patients who provided informed consent including 10 healthy controls, 19 known positive or negative controls, and 327 trauma patients older than 65 years who were evaluated at our large, urban level 1 trauma center. The assay methodology was developed in healthy and known controls to detect apixaban, rivaroxaban, and dabigatran using LCMS and then applied to 327 samples from trauma patients. Standard medication reconciliation processes in the electronic medical record documenting DOAC usage were compared with LCMS results to determine overall accuracy, sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of the assay. RESULTS: Of 356 patients, 39 (10.96%) were on DOACs: 21 were on apixaban, 14 on rivaroxaban, and 4 on dabigatran. The overall accuracy of the assay for detecting any DOAC was 98.60%, with a sensitivity of 94.87% and specificity of 99.05% (PPV, 92.50%; NPV, 99.37%). The assay detected apixaban with a sensitivity of 90.48% and specificity of 99.10% (PPV, 86.36%; NPV 99.40%). There were three false-positive results and two false-negative LCMS results for apixaban. Dabigatran and rivaroxaban were detected with 100% sensitivity and specificity. CONCLUSION: This LCMS-based assay was highly accurate in detecting DOACs in trauma patients. Further studies need to confirm the clinical efficacy of this LCMS assay and its value for medication reconciliation in trauma patients. LEVEL OF EVIDENCE: Diagnostic Test, level III.


Assuntos
Anticoagulantes/sangue , Espectrometria de Massas , Reconciliação de Medicamentos/métodos , Ferimentos e Lesões/sangue , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Cromatografia Líquida de Alta Pressão , Dabigatrana/administração & dosagem , Dabigatrana/sangue , Feminino , Voluntários Saudáveis , Humanos , Masculino , Estudos Prospectivos , Pirazóis/administração & dosagem , Pirazóis/sangue , Piridonas/administração & dosagem , Piridonas/sangue , Rivaroxabana/administração & dosagem , Rivaroxabana/sangue , Sensibilidade e Especificidade
10.
Prog Community Health Partnersh ; 13(3): 237-245, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564664

RESUMO

THE PROBLEM: Nationwide efforts to reduce smoking in the United States have been successful. Yet, there is unequal geographic progress in reducing rates of smoking and smoking-related illnesses. Located in a tobacco-producing state with weak tobacco laws, Nashville, Tennessee, has an adult smoking rate of 22.0%, requiring 45,000 smokers to quit to meet the Healthy People 2020 goal of 12%. PURPOSE: The purpose of this article was to detail the development a community-academic partnership (CAP) and its process for devising a local implementation strategy for tobacco control. KEY POINTS: Nashville's CAP developed with a community-based organization (CBOs) seeking out an academic partner. This unique approach addressed many of the challenges CAPs face, helped identify priorities and potential barriers to success and led to early wins. CONCLUSION: The success of Nashville's efforts suggests that CAPs should clearly delineate roles for members of the CAP, engage diverse stakeholders, be responsive to the community, and allow adequate time for planning and prioritizing.


Assuntos
Relações Comunidade-Instituição , Abandono do Hábito de Fumar/métodos , Adulto , Programas Gente Saudável/métodos , Humanos , Modelos Organizacionais , Fumar/epidemiologia , Tennessee/epidemiologia , Universidades/organização & administração , População Urbana/estatística & dados numéricos
12.
Int J Sport Nutr Exerc Metab ; 29(4): 359­363, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31141394

RESUMO

This study assessed voluntary dietary intake when different beverages were provided within a recovery area following recreational exercise. Participants completed two 10-km runs 1 week apart. Immediately after the first run, "beer drinkers" (n = 54; mean ± SD: age = 23.9 ± 5.8 years, body mass [BM] = 76 ± 13 kg) randomly received low-alcohol beer (Hahn Ultra® [Lion Co.], 0.9% alcohol by volume) or sports drink (SD; Gatorade® [PepsiCo]), whereas "nonbeer drinkers" (n = 78; age = 21.8 ± 2.2 years, BM = 71 ± 13 kg) received water or SD. Participants remained in a recovery area for 30-60 min with fluid consumption monitored. The following week, participants received the alternate beverage. Participants recorded all food/fluid consumed for the remainder of both trial days (diary and photographs). Fluid balance was assessed via BM change and urine specific gravity. Paired t tests were used to assess differences in hydration and dietary variables. No differences were observed in preexercise urine specific gravity (∼1.01) or BM loss (∼2%) between intervention groups (ps > .05). Water versus SD: No difference in acute fluid intake was noted (water = 751 ± 259 ml, SD = 805 ± 308 ml, p = .157). SD availability influenced total energy and carbohydrate intakes (water = 5.7 ± 2.5 MJ and 151 ± 77 g, SD = 6.5 ± 2.7 MJ and 187 ± 87 g, energy p = .002, carbohydrate p < .001). SD versus beer: SD availability resulted in greater acute fluid intake (SD = 1,047 ± 393 ml, beer = 850 ± 630 ml; p = .004), which remained evident at the end of trial days (SD = 3,337 ± 1,100 ml, beer = 2,982 ± 1,191 ml; p < .01). No differences in dietary variables were observed. Next day, urine specific gravity values were not different between water versus SD. However, a small difference was detected between SD versus beer (SD = 1.021 ± 0.009, beer = 1.016 ± 0.008, p = .002). Consuming calorie-containing drinks postexercise appears to increase daily energy and carbohydrate intake but has minimal impact on next-day hydration.


Assuntos
Bebidas/análise , Carboidratos da Dieta/administração & dosagem , Ingestão de Energia , Estado de Hidratação do Organismo , Corrida/fisiologia , Adolescente , Adulto , Atletas , Cerveja/análise , Feminino , Humanos , Soluções Isotônicas/análise , Masculino , Equilíbrio Hidroeletrolítico , Adulto Jovem
13.
J Clin Pathol ; 72(6): 399-405, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30910824

RESUMO

OBJECTIVE: Academic pathology is facing a crisis; an ongoing decline in academic pathology posts, a paucity of academic pathologist's in-training and unfilled posts at a time when cellular pathology departments are challenged to deliver increasing numbers of molecular tests. The National Cancer Research Institute initiative in Cellular & Molecular Pathology commissioned a survey to assess attitudes of cellular pathology consultants towards research in order to understand barriers and identify possible solutions to improve this situation. As cellular pathology is encompassing an increasing number of diagnostic molecular tests, we also surveyed the current approach to and extent of training in molecular pathology. METHODS: The survey was distributed to all UK-based consultant pathologists via the Pathological Society of Great Britain & Ireland and Royal College of Pathologist networks. Heads of Department were contacted separately to obtain figures for number of academic training and consultant posts. RESULTS: 302 cellular pathologists completed the survey which represents approximately 21% of the total cellular histopathology workforce. Most respondents (89%) had been involved in research at some point; currently, 22% were undertaking research formally, and 41% on an informal basis. Of those previously involved in research, 57% stopped early in their consultant career. The majority of substantive academic posts were Professors of which 60% had been in post for >20 years. Most respondents (84%) used molecular pathology in diagnostic work, independent of where they worked or the length of time in post. Notably, 53% of consultants had not received molecular pathology training, particularly more senior consultants and consultants in district general hospitals. CONCLUSIONS: The survey reveals that the academic workforce is skewed towards senior individuals, many of whom are approaching retirement, with a missing cohort of 'junior consultant' academic pathologists to replace them. Most pathologists stop formal research activity at the beginning of a consultant career. While molecular pathology is an increasing part of a pathologist's workload, the majority of consultant cellular pathologists have not received any formal molecular training.


Assuntos
Academias e Institutos , Atitude do Pessoal de Saúde , Pesquisa Biomédica , Consultores/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Patologistas/psicologia , Patologia Molecular , Academias e Institutos/tendências , Pesquisa Biomédica/tendências , Competência Clínica , Necessidades e Demandas de Serviços de Saúde , Mão de Obra em Saúde , Humanos , Descrição de Cargo , Avaliação das Necessidades , Patologistas/provisão & distribuição , Patologistas/tendências , Patologia Molecular/tendências , Aposentadoria , Inquéritos e Questionários , Reino Unido , Carga de Trabalho
14.
J Clin Pathol ; 72(6): 443-447, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30723092

RESUMO

Colorectal cancer (CRC) is common with 3% of cases associated with germline mutations in the mismatch repair pathway characteristic of Lynch syndrome (LS). The UK National Institute for Health and Care Excellence recommends screening for LS in all patients newly diagnosed with CRC, irrespective of age. The Yorkshire Cancer Research Bowel Cancer Improvement Programme includes a regional LS screening service for all new diagnoses of CRC. In the first 829 cases screened, 80 cases showed deficient mismatch repair (dMMR) including four cases showing areas with loss of expression of all four mismatch repair proteins by immunohistochemistry. The cases demonstrated diffuse MLH1 loss associated with BRAF mutations and MLH1 promoter hypermethylation in keeping with sporadic dMMR, with presumed additional double hit mutations in MSH2+/-MSH6 rather than underlying LS. Recognition and accurate interpretation of this unusual phenotype is important to prevent unnecessary referrals to clinical genetics and associated patient anxiety.


Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , Metilação de DNA , Proteínas de Ligação a DNA/análise , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/análise , Regiões Promotoras Genéticas , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Neoplasias Colorretais/patologia , Reparo de Erro de Pareamento de DNA , Detecção Precoce de Câncer/métodos , Inglaterra , Feminino , Predisposição Genética para Doença , Humanos , Imuno-Histoquímica , Masculino , Técnicas de Diagnóstico Molecular , Mutação , Fenótipo , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética
15.
Cell Death Discov ; 4: 113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30534421

RESUMO

Glioblastoma is the most common yet most lethal of primary brain cancers with a one-year post-diagnosis survival rate of 65% and a five-year survival rate of barely 5%. Recently the U.S. Food and Drug Administration approved a novel fourth approach (in addition to surgery, radiation therapy, and chemotherapy) to treating glioblastoma; namely, tumor treating fields (TTFields). TTFields involves the delivery of alternating electric fields to the tumor but its mechanisms of action are not fully understood. Current theories involve TTFields disrupting mitosis due to interference with proper mitotic spindle assembly. We show that TTFields also alters cellular membrane structure thus rendering it more permeant to chemotherapeutics. Increased membrane permeability through the imposition of TTFields was shown by several approaches. For example, increased permeability was indicated through increased bioluminescence with TTFields exposure or with the increased binding and ingress of membrane-associating reagents such as Dextran-FITC or ethidium D or with the demonstration by scanning electron microscopy of augmented number and sizes of holes on the cellular membrane. Further investigations showed that increases in bioluminescence and membrane hole production with TTFields exposure disappeared by 24 h after cessation of alternating electric fields thus demonstrating that this phenomenom is reversible. Preliminary investigations showed that TTFields did not induce membrane holes in normal human fibroblasts thus suggesting that the phenomenom was specific to cancer cells. With TTFields, we present evidence showing augmented membrane accessibility by compounds such as 5-aminolevulinic acid, a reagent used intraoperatively to delineate tumor from normal tissue in glioblastoma patients. In addition, this mechanism helps to explain previous reports of additive and synergistic effects between TTFields and other chemotherapies. These findings have implications for the design of combination therapies in glioblastoma and other cancers and may significantly alter standard of care strategies for these diseases.

16.
J Clin Pathol ; 71(4): 285-290, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29113995

RESUMO

The evolution of cellular pathology as a specialty has always been driven by technological developments and the clinical relevance of incorporating novel investigations into diagnostic practice. In recent years, the molecular characterisation of cancer has become of crucial relevance in patient treatment both for predictive testing and subclassification of certain tumours. Much of this has become possible due to the availability of next-generation sequencing technologies and the whole-genome sequencing of tumours is now being rolled out into clinical practice in England via the 100 000 Genome Project. The effective integration of cellular pathology reporting and genomic characterisation is crucial to ensure the morphological and genomic data are interpreted in the relevant context, though despite this, in many UK centres molecular testing is entirely detached from cellular pathology departments. The CM-Path initiative recognises there is a genomics knowledge and skills gap within cellular pathology that needs to be bridged through an upskilling of the current workforce and a redesign of pathology training. Bridging this gap will allow the development of an integrated 'morphomolecular pathology' specialty, which can maintain the relevance of cellular pathology at the centre of cancer patient management and allow the pathology community to continue to be a major influence in cancer discovery as well as playing a driving role in the delivery of precision medicine approaches. Here, several alternative models of pathology training, designed to address this challenge, are presented and appraised.


Assuntos
Patologistas/educação , Patologia Molecular/educação , Patologia Molecular/tendências , Humanos
17.
Ann Clin Biochem ; 52(Pt 6): 687-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26113739

RESUMO

The microbiome is the collective term used to describe the bacteria, viruses, fungi and archaea that reside on and in the human body. The majority of these organisms are found within the large bowel. Mounting evidence suggests that changes in the microbiome may be associated with the development of colorectal cancer, a disease which affects 1.3 million people a year worldwide. Using colorectal cancer as an example, this article presents the inter-specialty collaborative approach to microbiome research and discusses the key role that clinical biochemistry is likely to play.


Assuntos
Química Clínica , Comunicação Interdisciplinar , Microbiologia , Microbiota , Biologia Molecular , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/microbiologia , Neoplasias Colorretais/patologia , Humanos , Pessoa de Meia-Idade
18.
Clin Med Insights Oncol ; 8: 81-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25057245

RESUMO

BACKGROUND: The aim of the study is to investigate the prognostic role of pre-treatment of markers of the systemic inflammatory response (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin) in patients with oropharyngeal carcinoma treated with chemoradiotherapy. METHODS: A total of 251 patients with oropharyngeal squamous cell cancer treated with chemoradiotherapy between 2004 and 2010 were retrospectively identified. NLR, PLR, and albumin were recorded from baseline blood parameters. NLR threshold of >5 and PLR thresholds of ≤150, >150 and ≤300, and >300 were used for analysis. RESULTS: Median follow-up was 46 months (range 9-98). The 3 year overall survival, local control, regional control, and distant control were 70%, 85%, 87%, and 87%, respectively. On multivariate analysis, locoregional control was associated with T stage (HR 3.3 (95% CI 1.5-6.9), P = 0.002) and NLR (HR 2.1 (95% CI 1.1-3.9), P = 0.023). Overall survival was associated with T stage (HR 2.47 (95% CI 1.45-4.2), P = 0.001) and grade (HR 0.61 (95% CI 0.38-0.99), P = 0.048). PLR and albumin were not significantly associated with disease outcomes or survival. CONCLUSIONS: The NLR is an independent prognostic factor for locoregional control in oropharyngeal cancer treated with chemoradiotherapy.

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