Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice

Alikhan, Mahboob; Rex, Douglas K.; Khan, Abdul Haleem; Rahmani, Emad; Cummings, Oscar W.; Ulbright, Thomas M.

doi:10.1016/s0016-5107(99)70339-1

Cited by 168 publications

(95 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further work by that group examined 293 additional patients with LGD diagnosed in the community who had biopsies reviewed by at least 2 GI pathologists and 73% of the cases were downgraded to indefinite for dysplasia or nondysplastic BE ( 123 ). Other studies suggest that community-based pathologists have diffi culties in the interpretation of both nondysplastic BE and dysplasia ( 124 ). Th erefore, current evidence supports the importance of having all readings of dysplasia confi rmed by a second pathologist with extensive experience in the interpretation of Barrett's associated neoplasia.…”

Section: Advanced Endoscopic Imaging Techniquesmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

View full text Add to dashboard Cite

Recent population studies suggest that gastroesophageal refl ux disease (GERD) is increasing in prevalence, both in the United States and worldwide ( 1,2 ). Th e diagnosis of GERD is associated with a 10-15% risk of Barrett's esophagus (BE), a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia (IM). Risk factors associated with the development of BE include long-standing GERD, male gender, central obesity ( 3 ), and age over 50 years ( 4,5 ). Th e goal of a screening and surveillance program for BE is to identify individuals at risk for progression to esophageal adenocarcinoma (EAC), a malignancy that has been increasing in incidence since the 1970s ( 6,7 ).Th e purpose of this guideline is to review the defi nition and epidemiology of BE, available screening modalities for BE detection, rationale and methods for surveillance, and available treatment modalities including medical, endoscopic, and surgical techniques. In order to evaluate the level of evidence and strength of recommendations, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system ( 8 ). Th e level of evidence ranged from "high" (implying that further research was unlikely to change the authors' confi dence in the estimate of the eff ect) to "moderate" (further research would be likely to have an impact on the confi dence in the estimate of eff ect) to "low" (further research would be expected to have an important impact on the confi dence in the estimate of the eff ect and would be likely to change the estimate) or "very low" (any estimate of eff ect is very uncertain). Th e strength of a recommendation was graded as "strong" when the desirable eff ects of an intervention clearly outweighed the undesirable eff ects and as "conditional" when there was uncertainty about the tradeoff s. We used meta-analyses or systematic reviews when available, followed by clinical trials and cohort and case-control studies. In order to determine the level Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with refl ux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-defi nition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is ...

show abstract

Section: Advanced Endoscopic Imaging Techniquesmentioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,336

1,412

View full text Add to dashboard Cite

show abstract

“…These problems have included poor reproducibility of dysplasia interpretation (except for high-grade dysplasia (HGD)), poor predictive value for negative, indefinite, and low-grade dysplasia (LGD), and sampling error (Alikhan et al, 1999;Montgomery et al, 2001a, b). Moreover, multiple studies have shown that the majority of patients do not progress to dysplasia or carcinoma, with an annual rate of neoplastic transformation of BE to EAC of only 0.4-0.5% (Drewitz et al, 1997;Shaheen and Ransohoff, 2002).…”

Section: Introductionmentioning

confidence: 99%

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk

et al. 2005

View full text Add to dashboard Cite

Patients with Barrett's esophagus (BE) are at increased risk of developing esophageal adenocarcinoma (EAC). Clinical neoplastic progression risk factors, such as age and the length of the esophageal BE segment, have been identified. However, improved molecular biomarkers predicting increased progression risk are needed for improved risk assessment and stratification. Using realtime quantitative methylation-specific PCR, we screened 10 genes (HPP1, RUNX3, RIZ1, CRBP1, 3-OST-2, APC, TIMP3, p16, MGMT, p14) for promoter hypermethylation in 77 EAC, 93 BE, and 64 normal esophagus (NE) specimens. A subset of genes manifesting significant differences in methylation frequencies between BE and EAC was then analysed in 20 dysplastic specimens. All 10 genes except p14 were frequently methylated in EACs, with RUNX3, HPP1, CRBP1, RIZ1, and OST-2 representing novel methylation targets in EAC and/or BE. p16, RUNX3, and HPP1 displayed increasing methylation frequencies in BE vs EAC. Furthermore, these increases in methylation occurred early, at the interface between BE and low-grade dysplasia (LGD). To demonstrate the silencing effect of hypermethylation, we selected the EAC cells BIC1, in which the HPP1 promoter is natively methylated, and subjected them to 5-aza-2 0 -deoxycytidine (Aza-C) treatment. Real-time RT-PCR indicated increased HPP1 mRNA levels after 3 days of Aza-C treatment, as well as decreased levels of methylated HPP1 DNA. Hypermethylation of a subset of six genes (APC, TIMP3, CRBP1, p16, RUNX3, and HPP1) was then tested in a retrospective longitudinal study of 99 BE and nine LGD specimens obtained from 53 BE patients undergoing surveillance endoscopy. Only highgrade dysplasia (HGD) or EAC were defined as progression end points. Two patient groups were compared: eight progressors (P) and 45 nonprogressors (NP), using Cox proportional hazards models to determine the relative progression risks of age, BE segment length, and methylation events. Multivariate analyses revealed that only hypermethylation of p16 (odds ratio (OR) 1.74, 95% confidence interval (CI) 1.33-2.20), RUNX3 (OR 1.80, 95% CI 1.08-2.81), and HPP1 (OR 1.77, 95% CI 1.06-2.81) were independently associated with an increased risk of progression, whereas age, BE segment length, and hypermethylation of TIMP3, APC, or CRBP1 were not independent risk factors. In combined analyses, risk was detectable up to, but not earlier than, 2 years preceding neoplastic progression. Hypermethylation of p16, RUNX3, and HPP1 in BE or LGD may represent independent risk factors for the progression of BE to HGD or EAC. These findings have implications regarding risk stratification, early EAC detection, and the appropriate endoscopic surveillance interval for patients with BE.

show abstract

“…Apesar de a metaplasia intestinal, quando francamente presente, ser um diagnóstico com adequada reprodutibilidade (20) , o mesmo não ocorre para as displasias (1,10,14,21,29) , ponto de extrema relevância na tomada de decisões quanto ao acompanhamento clínico e à opção terapêutica entre doentes com EB.…”

Section: Discussionunclassified

“…Ainda assim, na experiência dos mesmos autores, embora a prevalência da p53 entre os doentes com DBG tenha sido o dobro daquela observada entre os sem displasia, o padrão de positividade foi idêntico, ficando exclusivamente às custas do diagnóstico histopatológico adequado à distinção entre os dois grupos. Contudo, na literatura (1,10,14,29) e na experiência dos autores do presente estudo (21) , o diagnóstico histopatológico, sobretudo para a DBG, ainda está longe de se mostrar ferramenta adequada, vista a precária reprodutibilidade tanto intra, como interobservador.…”

Section: Displasia Alto Grauunclassified

“…Quando da opção pelo programa de vigilância, a detecção da displasia ainda representa o padrão-ouro para a avaliação da progressão para o câncer ou para a detecção do próprio carcinoma in situ (18,26) . No entanto, embora considerada condição neoplásica inequívoca sobre certas circunstâncias, sua detecção apresenta certa ambigüidade no diagnóstico histopatológico, não apresenta nenhuma característica macroscópica específica e conta com imensa variação interobservador na avaliação histológica, além de poder apresentar resultados falso-negativos por erros de amostragem na coleta das biopsias (1,14,29) (10) . Assim, compreendendo-se a dificuldade em acompanhar com segurança os doentes com EB e de intervir precocemente antes da evolução para o adenocarcinoma, a literatura tem demonstrado grande apreço na busca de marcadores tumorais para detectar os casos de EB propensos ao desenvolvimento do câncer.…”

unclassified

See 1 more Smart Citation

O critério de positividade para a análise imunoistoquímica da p53 na confirmação da displasia do esôfago de Barrett faz diferença?

Lopes

Pereira-Lima

Hartmann

et al. 2005

Arq. Gastroenterol.

View full text Add to dashboard Cite

v. 42 -no. 4 -out./dez. 2005 Arq Gastroenterol 233 ARTIGO ORIGINAL / ORIGINAL ARTICLE ARQGA/1194INTRODUÇÃO O esôfago de Barrett (EB) é uma condição adquirida, presente em até 2% dos pacientes submetidos a esofagogastroduodenoscopia e em 10% a 15% dos doentes crônicos de sintomas de refluxo duodenogastroesofágico (4,8,10) , na qual uma extensão variável do epitélio escamoso esofágico é substituído por um epitélio colunar glandular, contendo células caliciformes (8,22,26,31) .A importância desta metaplasia reside no fato deste epitélio anômalo poder evoluir para o adenocarcinoma, com a doença sendo constatada, geralmente, em estádios avançados. A sobrevida média não costuma ultrapassar os 12 meses, com menos de 10% dos doentes contando com sobrevida superior a 5 anos (7,26) .Visto o adenocarcinoma apresentar incidência não desprezível e prognóstico reservado, recomenda-se vigilância endoscópica e histológica por toda a vida do paciente com epitélio de Barrett (26,31) . Quando da opção pelo programa de vigilância, a detecção da displasia ainda representa o padrão-ouro para a avaliação da progressão para o câncer ou para a detecção do próprio carcinoma in situ (18,26) . No entanto, embora considerada condição neoplásica inequívoca sobre certas circunstâncias, sua detecção apresenta certa ambigüidade no diagnóstico histopatológico, não apresenta nenhuma característica macroscópica específica e conta com imensa variação interobservador na avaliação histológica, além de poder apresentar resultados falso-negativos por erros de amostragem na coleta das biopsias (1,14,29) RESUMO -Racional -O esôfago de Barrett é uma complicação da doença do refluxo gastroesofágico com importante potencial de malignização. Relata-se que a expressão do marcador tumoral p53 se acentua com a progressão displasia-adenocarcinoma. Objetivo -Avaliar a expressão da p53 no epitélio de Barrett com presença ou não de displasia conforme dois critérios de positividade. Material e Métodos -O material foi constituído por biopsias endoscópicas de 42 doentes com esôfago de Barrett. Cortes histológicos foram corados pela hematoxilina-eosina, pelo PAS-alcian blue e avaliados quanto à expressão imunoistoquímica da p53. O diagnóstico de displasia foi firmado pela concordância entre três patologistas. �oram utilizados �oram utilizados �oram utilizados dois critérios de positividade para a p53: 1. a coloração de, pelo menos, metade dos núcleos e 2. o encontro de qualquer núcleo corado. Resultados -O número total de fragmentos foi de 229, com média de 5,4 por paciente. A displasia foi detectada em seis (14,3%) casos. Para diferentes critérios de positividade, a p53 foi detectada, respectivamente, em 5 (13,9%) e 14 (38,9%) com epitélio metaplásico não-displásico. Especificamente nos seis casos displásicos, a p53 foi detectada, conforme o critério de positividade, em um (16,7%) e quatro (66,7%) casos, respectivamente. Conclusões -Nesta pequena série, a expressão imunoistoquímica da p53, independente do critério de positividade, não foi de auxílio para a confirm...

show abstract

Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice

Cited by 168 publications

References 13 publications

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk

O critério de positividade para a análise imunoistoquímica da p53 na confirmação da displasia do esôfago de Barrett faz diferença?

Contact Info

Product

Resources

About