In this randomized trial involving 84,585 participants in Poland, Norway, and Sweden, the risk of colorectal cancer at 10 years was lower among those invited to undergo screening colonoscopy than ...among those assigned to no screening.
Recognition of early signet-ring cell carcinoma (SRCC) in patients with hereditary diffuse gastric cancer (HDGC) undergoing endoscopic surveillance is challenging. We hypothesized that probe-based ...confocal laser endomicroscopy (pCLE) might help diagnose early cancerous lesions in the context of HDGC. The aim of this study was to identify pCLE diagnostic criteria for early SRCC.
Patients with HDGC syndrome were prospectively recruited and pCLE assessment was performed on areas suspicious for early SRCC and control regions during an endoscopic surveillance procedure. Targeted biopsies were taken for gold standard histologic assessment. In Phase I two investigators assessed video sequences off-line to identify pCLE features related to SRCC. In Phase II pCLE diagnostic criteria were evaluated in an independent video set by the investigators blinded to the histologic diagnosis. Sensitivity, specificity, accuracy, and interobserver agreement were calculated.
Forty-two video sequences from 16 HDGC patients were included in Phase I. Four pCLE patterns associated to SRCC histologic features were identified: (A) glands with attenuated margins, (B) glands with spiculated or irregular shape, (C) heterogenous granular stroma with sparse glands, (D) enlarged vessels with tortuous shape. In Phase II, 38 video sequences from 15 patients were assessed. Criteria A and B and C had the highest diagnostic accuracy, with a κ for interobserver agreement ranging from 0.153 to 0.565. A panel comprising these 3 criteria with a cut-off of at least one positive criterion had a sensitivity of 80.9% (95%CI:58.1-94.5%) and a specificity of 70.6% (95%CI:44.0-89.7%) for a diagnosis of SRCC.
We have generated and validated off-line pCLE criteria for early SRCC. Future real-time validation of these criteria is required.
Current understanding of the risk of neoplastic progression in patients with Barrett's esophagus with indefinite dysplasia (BE-IND) stems from small retrospective and pathology registry studies. In ...this multicenter cohort study, we aimed to determine the incidence and prevalence of neoplasia in BE-IND.
Patients with confirmed BE-IND from 2 academic centers were included if they had no previous evidence of dysplasia and underwent endoscopic follow-up (FU) of ≥1 year. The rate of progression to neoplasia was calculated and categorized as prevalent (progression within 1 year of FU) and incident (progression after 1 year of FU). Multivariable regression adjusted for relevant clinical features was performed to identify risk factors for progression.
Four hundred sixty-five patients diagnosed with BE-IND were identified between 1997 and 2017, of which 223 (48.0%) were excluded. Of the remaining 242 patients, 184 (76.0%) had no evidence of dysplasia during FU. In 23 patients (9.5%), prevalent neoplasia occurred (20 low-grade dysplasia LGD, 2 high-grade dysplasia HGD, 1 intramucosal cancer IMC), whereas 35 patients (14.5%) developed incident neoplasia (27 LGD, 5 HGD, 3 IMC), after a median 1.5 years (interquartile range, 0.6-3.2 years). The incidence rates of any neoplasia and HGD/IMC were 3.2 and 0.6 cases/100 patient-years, respectively. BE length correlated with an increased risk of prevalent (odds ratio, 1.18 per 1 cm; 95% confidence interval, 1.02-1.38; P = .033) and incident neoplasia (odds ratio, 1.02; 95% confidence interval, 1.00-1.03; P = .016).
Patients with BE-IND should be closely monitored, because nearly a quarter harbor or will shortly develop dysplasia. BE length is a clinical predictor of neoplastic progression; however, more-accurate molecular biomarkers for risk stratification are warranted.
Aims
Barrett's oesophagus with indefinite for dysplasia (BE‐IND) is a subjective diagnosis with a low interobserver agreement (IOA) among pathologists and uncertain clinical implications. This study ...aimed to assess the utility of p53 immunohistochemistry (p53‐IHC) in assessing BE‐IND specimens.
Methods and results
Archive endoscopic biopsies with a BE‐IND diagnosis from two academic centres were analysed. First, haematoxylin and eosin‐stained slides (H&E) were reviewed by four expert gastrointestinal (GI) pathologists allocated into two groups (A and B). After a washout period of at least 8 weeks, H&E slides were reassessed side‐to‐side with p53‐IHC available. We compared the rate of changed diagnosis and the IOA for all BE grades before and after p53‐IHC. We included 216 BE‐IND specimens from 185 patients, 44.0 and 32.9% of which were confirmed after H&E slide revision by groups A and B, respectively. More than half the cases were reclassified to a non‐dysplastic BE (NDBE), while 5.6% of cases in group A and 7.4% in group B were reclassified to definite dysplasia. The IOA for NDBE, BE‐IND, low‐grade dysplasia (LGD) and high‐grade dysplasia (HGD)/intramucosal cancer (IMC) was 0.31, 0.21, −0.03 and −0.02, respectively. Use of p53‐IHC led to a >40% reduction in BE‐IND diagnoses (P < 0.001) and increased IOA for all BE grades κ = 0.46 (NDBE), 0.26 (BE‐IND), 0.49 (LGD), 0.35 (HGD/IMC). An aberrant p53‐IHC pattern significantly increased the likelihood of reclassifying BE‐IND to definite dysplasia (odds ratio = 44.3, 95% confidence interval = 18.8–113.0).
Conclusion
P53‐IHC reduces the rate of BE‐IND diagnoses and improves the IOA among pathologists when reporting BE with equivocal epithelial changes.
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