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3.
Arch Pathol Lab Med ; 146(1): 123-131, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34133708

RESUMO

CONTEXT.­: Competency-based medical education relies on frequent formative in-service assessments to ascertain trainee progression. Currently at our institution, trainees receive a summative end-of-rotation In-Training Evaluation Report based on feedback collected from staff pathologists. There is no method of simulating report sign-out. OBJECTIVE.­: To develop a formative in-service assessment tool that is able to simulate report sign-out and provide case-by-case feedback to trainees. Further, to compare time- versus competency-based assessment models. DESIGN.­: Twenty-one pathology trainees were assessed for 20 months. Hot Seat Diagnosis by trainees and trainee assessment by pathologists were recorded in the laboratory information system. In the first iteration, trainees were assessed by using a time-based assessment scale on their ability to diagnose, report, use ancillary tests, comment on clinical implications, and provide intraoperative consultation and/or gross cases. The second iteration used a competency-based assessment scale. Trainees and pathologists completed surveys on the effectiveness of the In-Training Evaluation Report versus the Hot Seat Diagnosis tool. RESULTS.­: Scores from both iterations correlated significantly with other assessment tools including the Resident In-Service Examination (r = 0.93, P = .04 and r = 0.87, P = .03). The competency-based model was better able to demonstrate improvement over time and stratify junior versus senior trainees than the time-based model. Trainees and pathologists rated Hot Seat Diagnosis as significantly more objective, detailed, and timely than the In-Training Evaluation Report, and effective at simulating report sign-out. CONCLUSIONS.­: Hot Seat Diagnosis is an effective tool for the formative in-service assessment of pathology trainees and simulation of report sign-out, with the competency-based model outperforming the time-based model.


Assuntos
Competência Clínica , Educação de Pós-Graduação em Medicina , Retroalimentação , Humanos , Inquéritos e Questionários
4.
Cancer Genomics Proteomics ; 18(5): 627-635, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34479915

RESUMO

BACKGROUND/AIM: Individual tumor genomics plays a key role in determining patient prognosis, response to chemotherapy and in guiding therapy. In prior studies, it was shown that the degree of late enhancement of colorectal liver metastases (CRCLM) target tumor enhancement (TTE) as seen on magnetic resonance imaging (MRI) was associated with overall survival. In order to better understand the relationship between MRI enhancement and survival, the aim of this study was to characterize genomic profiles of tumors clustered by MRI TTE, and investigate the association between TTE and genetic mutations. MATERIALS AND METHODS: Matched tumor and normal tissue samples from patients with weak TTE and strong TTE were analyzed by Next-generation sequencing (NGS) technology using a custom colorectal cancer panel. RESULTS: We discovered a total of 42 non-synonymous somatic mutations from 10 patients with weak TTE and 26 with 10 patients with strong TTE. Adenomatosis Polyposis Coli (APC) was the most commonly altered gene, 18 of those APC mutations were found in the weak TTE and 9 in the strong TTE group. CONCLUSION: An association exists between TTE and mutational status of CRCLM, which may offer some explanation as to why TTE is associated with overall survival in patients with CRCLM.


Assuntos
Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Mutação , Metástase Neoplásica , Estudos Retrospectivos
5.
Colorectal Dis ; 23(3): 635-645, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33058360

RESUMO

AIM: Factors associated with verified post-colonoscopy colorectal cancers (PCCRC) have not been well defined and survival for these patients is not well described. We aimed to assess the association of patient, tumour and endoscopist characteristics with PCCRC. METHODS: Using population-based data, we identified individuals diagnosed with CRC from 1 January 2000 to 31 December 2005 who underwent a colonoscopy within 3 years prior to diagnosis. Detected cancers were those diagnosed ≤6 months following colonoscopy; PCCRC were diagnosed >6 months to ≤3 years following colonoscopy. Post-colonoscopy and detected cancers were verified through chart review using a hospital-based simple random sampling frame. We used multivariable conditional logistic regression to determine the association of patient, tumour and endoscopist factors with PCCRC and compared overall survival using Cox proportional hazard models. RESULTS: Using the random sampling frame, we identified 498 patients with PCCRC and 498 with detected CRC; we obtained records and confirmed 367 patients with PCCRC and 412 with detected cancers. In multivariable analysis, patient age (OR 1.01; 95% CI 1.00-1.03) and tumour location (distal vs. proximal OR 0.36; 95% CI 0.25-0.53) were associated with PCCRC; endoscopist quality measures were not significantly associated with PCCRC. We did not find significant differences in overall survival between PCCRC and detected cancers (hazard ratio 1.12; 95% CI 0.92-1.32). CONCLUSION: Although endoscopic quality measures are important for CRC prevention, endoscopist factors were not associated with PCCRC. This study highlights the need for further research into the role of tumour biology in PCCRC development.


Assuntos
Neoplasias Colorretais , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Detecção Precoce de Câncer , Humanos , Modelos Logísticos , Estudos Retrospectivos , Fatores de Risco
6.
Diabetes Care ; 43(7): 1553-1556, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32345653

RESUMO

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, N = 1,298] vs. 4.7% [95% CI 3.4-5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI -0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4-2.7; P = 0.014) emerged with a GFD. CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.


Assuntos
Doença Celíaca/dietoterapia , Doença Celíaca/diagnóstico , Diabetes Mellitus Tipo 1/dietoterapia , Dieta Livre de Glúten , Adolescente , Adulto , Doenças Assintomáticas , Autoanticorpos/análise , Autoanticorpos/sangue , Biópsia , Glicemia/análise , Glicemia/metabolismo , Automonitorização da Glicemia , Canadá , Doença Celíaca/sangue , Doença Celíaca/complicações , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Período Pós-Prandial , Testes Sorológicos , Resultado do Tratamento , Adulto Jovem
7.
JAMA Surg ; 154(11): e193348, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31483457

RESUMO

Importance: Postoperative morbidity associated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) remains as high as 70%. However, to our knowledge, few studies have examined quality of life in this patient population. Objective: To identify symptom burden and trajectories and factors associated with high symptom burden following PD for PA. Design, Setting, and Participants: This population-based cohort study of patients undergoing PD for PA diagnosed between 2009 and 2015 linked population-level administrative health care data to routinely prospectively collected Edmonton Symptom Assessment System (ESAS) scores from 2009 to 2015, with a data analysis undertaken in 2018. Exposures: Baseline characteristics, including age, sex, income quintile, rurality, immigration status, and comorbidity burden, as well as treatment characteristics, including year of surgery and receipt of chemotherapy. Main Outcome and Measures: The outcome of interest was moderate to severe symptoms (defined as ESAS ≥4) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. The monthly prevalence of moderate to severe symptoms was presented graphically for each symptom. Multivariable regression models identified factors associated with the reporting of moderate to severe symptoms. Results: We analyzed 6058 individual symptom assessments among 615 patients with PA who underwent resection (285 women [46.3%]) with ESAS data. Tiredness (443 [72%]), impaired well-being (418 [68%]), and lack of appetite (400 [65%]) were most commonly reported as moderate to severe. The proportion of patients with moderate to severe symptoms was highest immediately after surgery (range, 14%-66% per symptom) and decreased over time, stabilizing around 3 months (range, 8%-42% per symptom). Female sex, higher comorbidity, and lower income were associated with a higher risk of reporting moderate to severe symptoms. Receipt of adjuvant chemotherapy was not associated with the risk of moderate to severe symptoms. Conclusions and Relevance: There is a high prevalence of symptoms following PD for PA, with improvement over the first 3 months following surgery. In what to our knowledge is the largest cohort reporting on symptom burden for this population, we have identified factors associated with symptom severity. These findings will aid in managing patients' perioperative expectations and designing strategies to improve targeted symptom management.


Assuntos
Adenocarcinoma/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/estatística & dados numéricos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos
8.
BMC Cancer ; 18(1): 884, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30200930

RESUMO

BACKGROUND: Sexually transmitted Human Papilloma Virus (HPV) infection is a known risk factor for cancer of the anal canal in both men and women. CASE PRESENTATION: We describe a report of synchronous carcinoma of the anal canal in a heterosexual couple. High risk type 16 HPV DNA was detected in both tumors. CONCLUSION: Longstanding sexual partners may share risk of HPV-associated anal canal cancer.


Assuntos
Neoplasias do Ânus/diagnóstico , Heterossexualidade , Neoplasias Primárias Múltiplas/diagnóstico , Parceiros Sexuais , Neoplasias do Ânus/etiologia , Biópsia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/etiologia , Papillomaviridae , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Tomografia Computadorizada por Raios X
9.
Eur Radiol ; 28(8): 3505-3512, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29476216

RESUMO

PURPOSE: To determine whether late gadolinium MRI enhancement of colorectal liver metastases (CRCLM) post-chemotherapy is associated with tumour fibrosis and survival post-hepatectomy. MATERIALS AND METHODS: The institutional review board approved this retrospective cohort study and waived the requirement for informed consent. A cohort of 121 surgical patients who received preoperative MRI after chemotherapy between 2006-2012 was included in this study. Target tumour enhancement (TTE), defined as the mean contrast-to-noise ratio of up to two target lesions on late-phase gadobutrol-enhanced MRI, was determined by two independent raters. The average TTE was correlated with tumour fibrosis on post-hepatectomy specimens using Spearman correlation and with survival post-hepatectomy using Kaplan-Meier and Cox regression. Inter-rater reliability was determined using relative intra-class correlation coefficients. RESULTS: In the surgical cohort (mean age: 63.0 years; male: 58%), TTE was associated with tumour fibrosis (r = 0.43, p < 0.001). Strong TTE was associated with improved survival compared to weak TTE (3-year survival: 88.4% vs. 58.8%, p = 0.003) with a hazard ratio of 0.32 (95% CI: 0.14-0.75, p = 0.008), after taking into account known prognostic variables. Inter-rater reliability was very good with a relative intraclass correlation of 0.84 (95% CI: 0.77-0.89). CONCLUSION: Late gadolinium MRI enhancement of CRCLM post-chemotherapy is associated with tumour fibrosis and survival. KEY POINTS: • MRI enhancement of colorectal liver metastases is associated with survival post-hepatectomy • MRI enhancement of chemotherapy-treated colorectal liver metastases correlates with tumour fibrosis • Measuring late MRI enhancement using target tumour enhancement is reliable.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia , Aumento da Imagem/métodos , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Compostos Organometálicos/farmacocinética , Idoso , Meios de Contraste/farmacocinética , Feminino , Fibrose , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Sobrevida
10.
J Cancer ; 6(5): 403-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25874002

RESUMO

Therapy with trastuzumab confers a survival benefit in HER2 positive advanced gastric and gastroesophageal adenocarcinoma. HER2 status is evaluated by immunohistochemistry (IHC) and in situ hybridization (ISH). An ISH ratio of HER2 to centromere 17 (CEP17) ≥2.0 is considered amplified. This assumes that CEP17 reflects chromosomal copy number. Cases where CEP17 exceeds 3 are classified as polysomic, but it's unknown if they represent true polysomy or centromeric amplification. This has implications on the validity of current ISH criteria. Multiplex ligation-dependent probe amplification (MLPA) allows simultaneous quantification of multiple loci and can distinguish between true polysomy and centromeric amplification. We selected 13 gastric cancers with CEP17 counts ≥3.0 (polyCEP17), and 8 non-polyCEP17 gastric cancer controls. Silver ISH for HER2 and CEP17 were performed and scored by manufacturer guidelines. We also performed an MLPA HER2 assay that evaluates 22 genes on chromosome 17. MLPA identified HER2 amplification in 7 polyCEP17 cases compared to 2 identified by ISH. Overall, 9 of 13 polyCEP17 cases had amplification of the peri-centromeric gene WSB1, compared to 1 of 8 non-polyCEP17 controls (p=0.02). This could account for ISH CEP17 counts ≥3.0. MLPA did not show any cases of complete chromosome 17 duplication and peri-centromeric amplification can explain most cases of ISH polyCEP17. Current ISH criteria may under-diagnose HER2 amplification in polyCEP17 cases due to flawed assumptions about polysomy. MLPA can detect HER2 amplification missed by IHC and ISH, and thus may be an effective ancillary technique in evaluating HER2 status.

12.
Am J Gastroenterol ; 109(11): 1698-704, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25001254

RESUMO

OBJECTIVES: The sessile serrated adenoma/polyp (SSA/P) is increasingly recognized as an important precursor to colorectal cancer (CRC) and may contribute to proximal postcolonoscopy CRCs. Hyperplastic polyps (HPs) generally follow a more benign course than do SSA/Ps, but they have a similar histologic appearance. Our aims were to identify patient and polyp factors associated with reclassification of HPs as SSA/Ps during a central pathology review and to characterize and compare their subsequent clinical management with other polyps. METHODS: From 2003 to 2008, we prospectively enrolled asymptomatic persons aged 50-74 years in a study of screening colonoscopy. Because criteria for SSA/P diagnosis evolved over our study period, we initiated a second review of all HPs >5 mm in size in 2011, with reclassification of polyps if indicated. Rates of subsequent colonoscopies, polypectomies, and CRCs were identified. RESULTS: We enrolled 2,527 persons who underwent colonoscopy in whom 111 had HPs >5 mm. Thirty-two of the 111 participants (28.8%) with HPs >5 mm had their polyps reclassified as SSA/Ps. There were no significant differences in patient characteristics between those with reclassified SSA/Ps and those who had HPs >5 mm. SSA/Ps were more likely to be proximal (P<0.001) and larger (P<0.007) than the HPs. In all, 48.3% of those with high-risk adenomas received appropriate follow-up compared with 26.1% of those with high-risk SSA/Ps. CONCLUSIONS: Almost 1/3 of recently diagnosed HPs >5 mm were reclassified as SSA/Ps. Patients previously diagnosed with larger HPs in the proximal colon may benefit from a pathologic review to ensure appropriate diagnosis and follow-up.


Assuntos
Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia , Neoplasias Colorretais/patologia , Lesões Pré-Cancerosas/diagnóstico , Adenoma/epidemiologia , Adenoma/cirurgia , Idoso , Pólipos do Colo/epidemiologia , Pólipos do Colo/cirurgia , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vigilância da População , Lesões Pré-Cancerosas/epidemiologia , Lesões Pré-Cancerosas/cirurgia , Estudos Prospectivos
13.
Gastrointest Endosc ; 80(4): 660-667, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24679656

RESUMO

BACKGROUND: Estimating risk for advanced proximal neoplasia (APN) based on distal colon findings can help identify asymptomatic persons who should undergo examination of the proximal colon after flexible sigmoidoscopy (FS) screening. OBJECTIVE: We aimed to determine the risk of APN by most advanced distal finding among an average-risk screening population. DESIGN: Prospective, cross-sectional study. SETTING: Teaching hospital and colorectal cancer screening center. PATIENTS: A total of 4651 asymptomatic persons at average risk for colorectal cancer aged 50 to 74 years (54.4% women [n = 2529] with a mean [± standard deviation] age of 58.4 ± 6.2 years). INTERVENTIONS: All participants underwent a complete colonoscopy, including endoscopic removal of all polyps. MAIN OUTCOME MEASUREMENTS: We explored associations between several risk factors and APN. Logistic regression was used to identify independent predictors of APN. RESULTS: A total of 142 persons (3.1%) had APN, of whom 85 (1.8%) had isolated APN (with no distal findings). APN was associated with older age, a BMI >27 kg/m(2), smoking, distal advanced adenoma and/or cancer, and distal non-advanced tubular adenoma. Those with a distal advanced neoplasm were more than twice as likely to have APN compared with those without distal lesions. LIMITATIONS: Distal findings used to estimate risk of APN were derived from colonoscopy rather than FS itself. CONCLUSION: In persons at average risk for colorectal cancer, the prevalence of isolated APN was low (1.8%). Use of distal findings to predict APN may not be the most effective strategy. However, incorporating factors such as age (>65 years), sex, BMI (>27 kg/m(2)), and smoking status, in addition to distal findings, should be considered for tailoring colonoscopy recommendations. Further evaluation of risk stratification approaches in other asymptomatic screening populations is warranted.


Assuntos
Colo Ascendente/patologia , Neoplasias do Colo/epidemiologia , Neoplasias do Colo/patologia , Colonoscopia/métodos , Detecção Precoce de Câncer/métodos , Distribuição por Idade , Idoso , Assistência Ambulatorial , Canadá/epidemiologia , Estudos de Coortes , Neoplasias do Colo/diagnóstico , Intervalos de Confiança , Estudos Transversais , Progressão da Doença , Feminino , Seguimentos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Razão de Chances , Prevalência , Estudos Prospectivos , Medição de Risco , Distribuição por Sexo , Sigmoidoscopia/métodos
14.
Hum Pathol ; 45(5): 970-5, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24656529

RESUMO

In advanced gastric and gastroesophageal junction (GEJ) adenocarcinomas that overexpress human epidermal growth factor receptor 2 (HER2), treatment with trastuzumab confers a survival benefit. To select patients for treatment, HER2 status is evaluated by immunohistochemistry (IHC) and in situ hybridization. Gastric and GEJ adenocarcinomas demonstrate heterogeneity in HER2 expression. Nonetheless, testing is often performed on biopsies alone, which raises the issue of nonrepresentative sampling. We investigated the correlation of HER2 status between matched biopsy and resection specimens and the role of tumor heterogeneity in contributing to discrepancy. A total of 128 patients with gastric or GEJ adenocarcinoma had tissue available from a biopsy and subsequent resection. HER2 IHC was performed and evaluated by the criteria used in the Trastuzumab for Gastric Cancer clinical trial. In situ hybridization was performed if IHC was equivocal (2+) in either the biopsy or resection and in discrepant cases. Tumor heterogeneity was defined as 3+ or 2+ staining in 10% to 60% of tumor cells. Overall, HER2 was overexpressed in 18 tumors (14%), with a biopsy-resection concordance of 96.1%. Five cases were discrepant; 2 were positive on biopsy only, and 3 were positive on resection only. Tumor heterogeneity was seen in 80% of discrepant biopsies and resections, compared with 24% of concordant cases (P = .016). Our study demonstrates strong concordance between biopsy and resection specimens for HER2 overexpression in gastric cancer. Discordance was correlated with tumor heterogeneity. Overall, both biopsy and resection specimens are appropriate for HER2 testing, but generous sampling for biopsy specimens is necessary to ensure accurate assessment.


Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/fisiopatologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/fisiopatologia , Receptor ErbB-2/biossíntese , Neoplasias Gástricas/patologia , Neoplasias Gástricas/fisiopatologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/uso terapêutico , Biópsia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Junção Esofagogástrica/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Trastuzumab
15.
Can J Gastroenterol ; 25(10): 543-6, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22059158

RESUMO

BACKGROUND: Helicobacter pylori is a WHO class I carcinogen also associated with nonmalignant gastrointestinal diseases. Effective treatment exists, and all persons infected with H pylori should receive treatment. However, data regarding the rates of treatment prescription in clinical practice are lacking. OBJECTIVE: To determine the rates of H pylori treatment in usual practice. METHODS: Patients with histological evidence of H pylori infection between January 1, 2007, and December 31, 2007, at Sunnybrook Health Sciences Centre (Toronto, Ontario) were identified. Charts were reviewed to determine the rates of H pylori treatment and confirmation of eradication, when indicated. Questionnaires were subsequently sent to endoscopists of patients identified as not having received treatment to determine the reasons for lack of treatment. RESULTS: A total of 102 patients were H pylori positive and were appropriate candidates for treatment, of whom 58 (57%) were male and 78 (76%) were outpatients, with 92 (90%) receiving eradication therapy. When indicated, 15 of 22 (68%) patients received confirmation of eradication, 13 of 18 (72%) patients underwent repeat endoscopy and 86% received complete therapy. Outpatients were more likely to receive eradication therapy (OR 10.3 [95% CI 2.6 to 40.4]; P=0.001) and complete therapy (OR 13.2 [95% CI 3.8 to 45.7]; P=0.0001) compared with inpatients. Having a follow-up appointment resulted in higher treatment rates (OR 12.0 [95% CI 3.0 to 47.5]; P=0.001). CONCLUSION: During the time period studied, adequate rates of H pylori treatment were achieved in outpatients and patients who had formal follow-up at Sunnybrook Health Sciences Centre. However, some aspects of care remain suboptimal including treatment of inpatients and care following treatment. Additional studies are required to identify strategies to improve the care of patients infected with H pylori.


Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Padrões de Prática Médica/normas , Idoso , Assistência Ambulatorial/normas , Endoscopia Gastrointestinal , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
16.
J Crohns Colitis ; 4(2): 207-10, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21122508

RESUMO

Desmoids are rare tumors resulting from the proliferation of fibroblasts. They occur in association with familial adenomatous polyposis (FAP), but they may also occur in the post-traumatic peri-partum or post-abdominal surgery setting, and a few present spontaneously. Presenting features of desmoids are protean and largely relate to the anatomical area of involvement. We describe a 50 year old male not known to have Crohn's disease and without FAP who presented with multiple desmoids. Investigation of post-operative diarrhea confirmed a diagnosis of Crohn's disease. This is the first report of a male patient, who had never undergone prior abdominal surgery, presenting with Crohn's disease and abdominal desmoid tumors. The reasons why Crohn's disease and desmoids may be associated are explored, focusing particularly on alternations in the fibrogenic cytokine TGF-ß now known to be involved in the pathogenesis of both diseases.


Assuntos
Doença de Crohn/complicações , Doença de Crohn/fisiopatologia , Fibromatose Abdominal/etiologia , Fibromatose Abdominal/fisiopatologia , Doença de Crohn/diagnóstico , Doença de Crohn/terapia , Fibromatose Abdominal/diagnóstico , Fibromatose Abdominal/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Transformador beta/metabolismo , Resultado do Tratamento
17.
Diabetes ; 58(4): 1007-17, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19168599

RESUMO

OBJECTIVE: Two type 1 diabetes susceptibility genes have been identified in the spontaneously diabetic biobreeding diabetes-prone (BBDP) rat, the major histocompatibility complex (MHC) (RT1) class II u haplotype (Iddm1) and Gimap5 (Iddm2). The strong effects of these have impeded previous efforts to map additional loci. We tested the hypothesis that type 1 diabetes is a polygenic disease in the BBDP rat. RESEARCH DESIGN AND METHODS: We performed the most comprehensive genome-wide linkage analysis for type 1 diabetes, age of disease onset (AOO), and insulitis subphenotypes in 574 F2 animals from a cross-intercross between BBDP and type 1 diabetes-resistant, double congenic ACI.BBDP-RT1u,Gimap5 (ACI.BB(1u.lyp)) rats, where both Iddm1 and Iddm2 were fixed as BBDP. RESULTS: A total of 19% of these F2 animals developed type 1 diabetes, and eight type 1 diabetes susceptibility loci were mapped, six showing significant linkage (chromosomes 1, 3, 6 [two loci], 12, and 14) and two (chromosomes 2 and 17) suggestive linkage. The chromosomes 6, 12, and 14 intervals were also linked to the severity of islet infiltration by immunocytes, while those on chromosomes 1, 6 (two loci), 14, 17, and a type 1 diabetes-unlinked chromosome 8 interval showed significant linkage to the degree of islet atrophy. Four loci exhibited suggestive linkage to AOO on chromosomes 2 (two loci), 7, and 18 but were unlinked to type 1 diabetes. INS, PTPN22, IL2/IL21, C1QTNF6, and C12orf30, associated with human type 1 diabetes, are contained within the chromosomes 1, 2, 7, and 12 loci. CONCLUSIONS: This study demonstrates that the BBDP diabetic syndrome is a complex, polygenic disease that may share additional susceptibility genes besides MHC class II with human type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1/genética , Ratos Endogâmicos BB/genética , Animais , Mapeamento Cromossômico , Cruzamentos Genéticos , Modelos Animais de Doenças , Intervalo Livre de Doença , Genoma , Glicosúria , Humanos , Modelos Genéticos , Ratos
18.
Int J Surg Pathol ; 15(3): 252-7, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17652531

RESUMO

The immunoexpression of CK19 recently has been identified as a marker of poor prognosis in pancreatic endocrine tumors and hepatocellular carcinoma. Conversely, the loss of expression of CD99 has been suggested to play a role in the tumorigenesis and dedifferentiation and is associated with poor outcome in some malignancies. The purpose of this study was to explore CK19 and CD99 immunostaining in mucin-producing neuroendocrine (goblet cell) and classical carcinoids of the appendix. Eighteen goblet cell carcinoids (GCCs) and 20 classic carcinoids were stained with CK19, CD99, and Ki-67, and these results were correlated with known pathological features of aggression: extent of invasion, mitoses, necrosis, and histological pattern. All 18 GCCs were CK19 strongly positive, whereas 16/20 classic carcinoids were also CK19 positive. Fourteen of 18 GCCs and 14/20 classic carcinoids were CD99 positive. CK19/CD99 immunoexpression did not correlate with extent of tumor invasion and mesoappendiceal extension, mitotic activity, Ki-67 labeling index, presence of extracellular mucinous pools dissecting muscle, and angiolymphatic and perineural/neural invasion. There is no difference in the immunostaining for CK19 and CD99 between GCCs and classic carcinoids, and both types of neuroendocrine tumor show the same extent of expression of both markers.


Assuntos
Antígenos CD/metabolismo , Neoplasias do Apêndice/metabolismo , Tumor Carcinoide/metabolismo , Moléculas de Adesão Celular/metabolismo , Queratina-19/metabolismo , Antígeno 12E7 , Antígenos CD/genética , Neoplasias do Apêndice/patologia , Biomarcadores Tumorais/metabolismo , Tumor Carcinoide/patologia , Moléculas de Adesão Celular/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Queratina-19/genética , Invasividade Neoplásica/patologia
19.
Diabetes ; 56(6): 1731-6, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17389329

RESUMO

OBJECTIVE: The biobreeding diabetes-prone (BBDP) rat spontaneously develops type 1 diabetes. Two of the genetic factors contributing to this syndrome are the major histocompatibility complex (Iddm1) and a Gimap5 mutation (Iddm2) responsible for a T-lymphopenia. Susceptibility to experimentally induced type 1 diabetes is widespread among nonlymphopenic (wild-type Iddm2) rat strains provided they share the BBDP Iddm1 allele. The question follows as to whether spontaneous and experimentally induced type 1 diabetes share susceptibility loci besides Iddm1. Our objectives were to map a novel, serendipitously discovered Iddm locus, confirm its effects by developing congenic sublines, and assess its differential contribution to spontaneous and experimentally induced type 1 diabetes. RESEARCH DESIGN AND METHODS: An unexpected reduction in spontaneous type 1 diabetes incidence (86 to 31%, P < 0.0001) was observed in a BBDP line congenic for a Wistar Furth-derived allotypic marker, RT7 (chromosome 13). Genome-wide analysis revealed that, besides the RT7 locus, a Wistar Furth chromosome 8 fragment had also been introduced. The contribution of these intervals to diabetes resistance was assessed through linkage analysis using 134 F2 (BBDP x double congenic line) animals and a panel of congenic sublines. One of these sublines, resistant to spontaneous type 1 diabetes, was tested for susceptibility to experimentally induced type 1 diabetes. RESULTS: Both linkage analysis and congenic sublines mapped a novel locus (Iddm24) to the telomeric 10.34 Mb of chromosome 8, influencing cumulative incidence and age of onset of spontaneous type 1 diabetes but not insulitis nor experimentally induced type 1 diabetes. CONCLUSIONS: This study has identified a type 1 diabetes susceptibility locus that appears to act after the development of insulitis and that regulates spontaneous type 1 diabetes exclusively.


Assuntos
Mapeamento Cromossômico , Diabetes Mellitus Experimental/epidemiologia , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Animais , Diabetes Mellitus Experimental/genética , Modelos Animais de Doenças , Ratos , Ratos Endogâmicos BB , Telômero/genética
20.
HPB (Oxford) ; 9(5): 388-91, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18345324

RESUMO

BACKGROUND: Lymph node status is an important prognostic factor in pancreatic and peri-ampullary adenocarcinoma. We recently changed our protocol for assessment of the uncinate margin of Whipple specimens and noted that lymph nodes were often present in uncinate margin sections. MATERIALS AND METHODS: Whipple specimens from 2004 to 2006 were divided into two groups, those that were handled according to the en face protocol, and those handled according to the radial protocol. The numbers of lymph nodes found in uncinate margin sections were assessed, as well as the total number of nodes found in the specimen. RESULTS: Sixteen cases were handled according to the en face protocol, and 20 according to the radial protocol. In the en face group, 2 benign nodes were found in the uncinate margin (0.1 nodes per case), while in the radial group, 36 nodes (1.8 nodes per case) were identified (p=0.0005). Eight cases in the latter group had positive nodes in the uncinate margin sections. In two of these cases the positive lymph node was the only lymph node with metastasis, and in an additional case the involved node was one of two positive lymph nodes. Total lymph node retrieval was 15.5 lymph nodes per case in the en face group, and 20 nodes per case in the radial group (p=0.02). DISCUSSION: The improved lymph node retrieval may be due to additional nodes found in radial sections of the uncinate margin, or alternatively, due to increased vigilance in specimen handling. In 3 of 20 cases, nodes found in the radial sections influenced staging.

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