Histopathologist Features Predictive of Diagnostic Concordance at Expert Level Amongst a Large International Sample of Pathologists Diagnosing Barrett’s Dysplasia Using Digital Pathology

Objective Guidelines mandate expert pathology review of Barrett’s oesophagus (BO) biopsies that reveal dysplasia, but there are no evidence-based standards to corroborate expert reviewer status. We investigated BO concordance rates and pathologist features predictive of diagnostic discordance. Design Pathologists (n=51) from over 20 countries assessed 55 digitised BO biopsies from across the diagnostic spectrum, before and after viewing matched p53 labelling. Extensive demographic and clinical experience data were obtained via online questionnaire. Reference diagnoses were obtained from a review panel (n=4) of experienced Barrett’s pathologists. Results We recorded over 6000 case diagnoses with matched demographic data. Of 2805H&E diagnoses, we found excellent concordance (>70%) for nondysplastic BO and high-grade dysplasia, and intermediate concordance for low-grade dysplasia (42%) and indefinite for dysplasia (23%). Major diagnostic errors were found in 248 diagnoses (8.8%), which reduced to 232 (8.3%) after viewing p53 labelled slides. Demographic variables correlating with diagnostic proficiency were analysed in multivariate analysis, which revealed that at least 5 years of professional experience was protective against major diagnostic error for H&E slide review (OR 0.48, 95% CI 0.31 to 0.74). Working in a non-teaching hospital was associated with increased odds of major diagnostic error (OR 1.76, 95% CI 1.15 to 2.69); however, this was neutralised when pathologists viewed p53 labelled slides. Notably, neither case volume nor self-identifying as an expert predicted diagnostic proficiency. Extrapolating our data to real-world case prevalence suggests that 92.3% of major diagnostic errors are due to overinterpreting non-dysplastic BO. Conclusion Our data provide evidence-based criteria for diagnostic proficiency in Barrett’s histopathology

¹⁸F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction:Accuracy and Long-Term Implications

Purpose : The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10–40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR. Methods: Four hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens. Results: Of the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival. Conclusion: Patients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.</p

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett’s esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett’s Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%–88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients

Endoscopic management and follow-up of patients with a submucosal esophageal adenocarcinoma

Introduction: The risk of lymph node metastases (LNM) in submucosal esophageal adenocarcinoma (EAC) patients is subject to debate. These patients might be treated endoscopically if the risk of LNM appears to be low. Objective: The objective of this article is to evaluate the outcome of patients who underwent an endoscopic resection (ER) and subsequent endoscopic follow-up for a submucosal EAC. Methods: All patients who underwent ER for submucosal EAC between January 2012 and August 2016 and were subsequently managed with endoscopic follow-up were retrospectively identified. Primary outcome was the number of patients diagnosed with LNM; secondary outcomes included intraluminal recurrences. Results: Thirty-five patients (median age 68 years) were included: 17 low-risk (submucosal invasion 500 microns, and/or G3-G4, and/or LVI, and/or a tumor-positive deep resection margin (R1)) EACs. After a median follow-up of 23 (IQR 15-43) months, in which patients underwent a median of six (IQR 4-8) endoscopies and a median of four (IQR 2-8) endoscopic ultrasound procedures, none of the included patients were diagnosed with LNM. Five (14%) patients developed a local intraluminal recurrence a median of 18 (IQR 11-21) months after baseline ER that were treated endoscopically. Conclusions: In 35 patients with a submucosal EAC, no LNM were found during a median follow-up of 23 months. Endoscopic therapy may be an alternative for surgery in selected patients with a submucosal EAC

A comparative analysis by SAGE of gene expression profiles of Barrett's esophagus, normal squamous esophagus, and gastric cardia

Background & Aims: The metaplastic process In which the normal squamous epithelium of the distal esophagus is replaced by columnar-lined epithelium, known as Barrett's esophagus (BE), is poorly understood. The aim of this study was to define, analyze, and compare transcription profiles of BE, normal cardia epithelium, and squamous epithelium to gain more Insight into the process of metaplasia and to identify uniquely expressed genes in these epithelia. Methods: Serial analysis of gene expression was applied for obtaining transcription libraries of biopsy specimens taken from a BE-affected patient with intestinal type of metaplasia and from normal squamous and gastric cardia epithelia. Validation of results by reverse-transcription polymerase chain reaction and immunoblotting was performed using tissues of 20 patients with BE. Results: More than :120,000 tags were sequenced. Between BE and squamous 776, and between BE and gastric cardia 534 tags were significantly differentially expressed (

Forward-viewing versus oblique-viewing echoendoscopes in transluminal drainage of pancreatic fluid collections: a multicenter, randomized, controlled trial

EUS-guided drainage of pancreatic fluid collections (PFCs) is commonly performed with oblique-viewing echoendoscopes. However, accessing the PFC under an oblique angle can make drainage difficult. These difficulties might be overcome by using a forward-viewing echoendoscope

Accuracy and reproducibility of 3D-CT measurements for early response assessment of chemoradiotherapy in patients with oesophageal cancer

AbstractBackgroundChemoradiotherapy is increasingly applied in patients with oesophageal cancer. The aim of the present study was to determine whether 3D-CT volumetry is able to differentiate between responding and non-responding oesophageal tumours early in the course of neoadjuvant chemoradiotherapy.Patients and methodsSerial CT before and after two weeks of neoadjuvant chemoradiotherapy was performed in the multimodality treatment arm of a randomised trial including patients with oesophageal carcinoma. CT response was measured with the change in tumour volume between baseline and after 14 days of neoadjuvant therapy. Receiver Operating Characteristic (ROC) analysis was used to evaluate the ability of 3D-CT as an early imaging marker of response.ResultsCT response analysis was performed in 39 patients, of whom 26 patients were histopathological responders. Median tumour volume increased between baseline and after 14 days of chemoradiotherapy in histopathological responders as well as in non-responders, though changes were not statistically significant. The area under the ROC curve was 0.71.ConclusionTumour volume changes after 14 days of neoadjuvant chemoradiotherapy as measured by 3D-CT were not associated with histopathological tumour response. CT volumetry should not be used for early response assessment in patients with potentially curable oesophageal cancer treated with neoadjuvant chemoradiotherapy

Supplementary Table 1 -Supplemental material for Development of benchmark quality criteria for assessing whole-endoscopy Barrett's esophagus biopsy cases

<p>Supplemental material, Supplementary Table 1 for Development of benchmark quality criteria for assessing whole-endoscopy Barrett's esophagus biopsy cases by MJ van der Wel, LC Duits, E Klaver, RE Pouw, CA Seldenrijk, GJA Offerhaus, M Visser, FJW ten Kate, JG Tijssen, JJGHM Bergman and SL Meijer in United European Gastroenterology Journal</p