scholarly journals Novel Pathologic Factors for Risk Stratification of Gastric “Indefinite for Dysplasia” Lesions

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Kwangil Yim ◽  
Jung Ha Shin ◽  
Jinyoung Yoo ◽  
Stephen Fink
Keyword(s):  
Image Analysis ◽  
Risk Stratification ◽  
Endoscopic Resection ◽  
Final Diagnosis ◽  
Low Grade ◽  
Test Set ◽  
Indefinite For Dysplasia ◽  
Validation Set ◽  
Nuclear Polarity

Background/Aims. “Indefinite for dysplasia” (IND) conditions of the stomach have high malignancy rates (22.6%–75.0%). Endoscopic resection is sometimes used for follow-up, but criteria for selecting this follow-up method are not established. We investigated pathologic factors to subclassify the IND of the stomach and select appropriate follow-up methods. Methods. In total, 123 IND cases with final diagnoses of cancer (29.3%), high-grade dysplasia (6.5%), low-grade dysplasia (11.4%), and nonneoplasm (52.8%) were randomly divided into test set ( n = 27 ) and validation set ( n = 96 ). By the image analysis, size, pleomorphism, hyperchromasia, irregularity of nuclei, and ratios of structural atypia area (SAA) to total IND area were measured in the test set. Using the validation set, consensus meetings were held for the evaluation of pathologic factors that predict the final diagnosis. Results. By image analysis, the only ratio of SAA to total IND area was associated with the final diagnosis ( p < 0.001 ). In the consensus meeting for validation, the nuclear factors, except loss of nuclear polarity ( p = 0.004 – 0.026 ), could not predict the final diagnosis. Conversely, most structural factors could predict the final diagnosis. In particular, SAA > 25 % was the most powerful predictive factor. We proposed criteria of risk stratification by using SAA > 25 % , loss of surface maturation (LOSM), and loss of nuclear polarity (LONP) (Malignancy rate; Category 0: SAA ≤ 25 % without LOSM and LONP; 0%, Category 1: SAA ≤ 25 % with any of LOSM or LONP; 15.2%–16.7%, Category 2: SAA > 25 % without LOSM and LONP; 44.4%–50.0%, Category 3: SAA > 25 % with any of LOSM or LONP 54.5%–55.6%). Conclusions. Structural atypia was more helpful than nuclear atypia and SAA > 25 % was the most powerful predictor for the diagnosis of INDs of the stomach. We propose shortening the follow-up period to six months for Category 1, endoscopic resection for Category 2 and 3, postresection follow-up periods of one year for Category 2, and six months for Category 3.

Detection of any-stage cancer using plasma and urine glycosaminoglycans.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3034-3034
Author(s):  
Francesco Gatto ◽  
Sinisa Bratulic ◽  
Ilaria Teresa Rita Cavarretta ◽  
Massimo Alfano ◽  
Francesca Maccari ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Cox Regression ◽  
Early Stage ◽  
Healthy Adults ◽  
Low Grade ◽  
Cancer Type ◽  
Liquid Biopsies ◽  
Non Invasive ◽  
Validation Set

3034 Background: Non-invasive liquid biopsies promise to enable early cancer detection and improve patient outcomes. However, virtually all liquid biopsies rely on genomic biomarkers, with limited sensitivity to early-stage tumors and poor detection of cancers shedding little cell-free DNA, like genitourinary or brain tumors. Here, we explored the use of plasma and urine glycosaminoglycan (GAGs) profiles, or GAGomes, as biomarkers reflective of tumor metabolism to serve as an alternative pan-cancer liquid biopsy. Methods: In this case-control study, we enrolled retrospective and prospective cohorts from Sweden and Italy. Included cases were treatment-naïve early-stage/low-grade cancers or metastatic/high-grade cancers across 14 histological types. Included controls were healthy 22-78 y/o adults with no history of cancer. We measured GAGomes – encompassing 17 chondroitin sulfate (CS), heparan sulfate (HS), and hyaluronate (HA) disaccharides - using a standardized UHPLC-MS/MS-based kit in a central blind laboratory. We tested the top GAGome features different in cancer using Bayesian estimation. These were used to design one plasma and one urine GAG score for the binary classification of cancer vs. control in a discovery set. We computed the area-under-the-curve (AUC), and sensitivity at 98% specificity of each GAG score in the validation set. A subset analysis was performed in early-stage/low-grade cancers only. In the subset of cases with survival records, we used multivariable Cox regression to estimate the hazard ratio (HR) for overall survival (OS) on each GAG score adjusted for cancer type, age, and gender. Results: GAGomes were measured in 753 plasma samples (460 cancers across 14 types, median age = 66 y/o, 51% female vs. 293 healthy adults, median age = 58 y/o, 57% female) and 559 urine samples (219 cancers across 5 types, median age = 69 y/o, 23% female vs. 340 healthy adults, median age = 56 y/o, 60% female). In the discovery set, the urine GAG score had an AUC = 0.80 (95% CI: 0.74-0.85, 124 cancers across 5 types vs. 184 controls) while the plasma GAG score had an AUC = 0.82 (95% CI: 0.78-0.86, 153 cancers across 14 types vs. 282 controls). In the validation set, the urine GAG score had an AUC = 0.78 (95% CI: 0.71-0.84, 95 cancers across 5 types vs. 156 controls) with 35% sensitivity at 98% specificity. The plasma GAG score had an AUC = 0.84 (95% CI: 0.79-0.88, 178 cancers across 14 types vs. 140 controls) with 41% sensitivity at 98% specificity. In the subset of early-stage/low-grade cancers, the AUC was 0.78 and 0.72 in plasma and urine, respectively. The plasma and urine GAG scores were independent predictors of OS regardless of cancer type (HR = 1.39, p = 0.005 in plasma [ N = 283, 11 types, 67 deaths, median follow-up 17 months] and HR = 1.53, p = 0.016 in urine [ N = 161, 4 types, 32 deaths, median follow-up 15 months]). Conclusions: GAGomes were sensitive non-invasive metabolic biomarkers for any-stage cancer, including genitourinary and brain tumors.

Concordance of Intradepartmental Consultations of Barrett’s Dysplasia

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S54-S55
Author(s):  
Fengming Chen ◽  
Yongjun Liu ◽  
Francesca Ruggiero
Keyword(s):  
Patient Management ◽  
Clinical Information ◽  
Final Diagnosis ◽  
Progression Rate ◽  
Low Grade ◽  
Rate Of Progression ◽  
Major Discrepancy ◽  
A Minor ◽  
Optimal Patient Management

Abstract Introduction Barrett’s esophagus (BE) is a well-known precursor to esophageal adenocarcinoma (EAC). Simple BE has an annual rate of progression to EAC of only up to 0.5%, while BE with low-grade dysplasia (LGD) or with high-grade dysplasia (HGD) has a higher progression rate of ~10% and ~40%, respectively. Therefore, accurate diagnosis and grading of dysplasia in BE are critical for optimal patient management. However, grading dysplasia is not well defined in practice, which often results in poor interobserver and/or intraobserver reproducibility. In this study, we aim to (1) investigate the concordance of intradepartmental consultations of BE dysplasia and (2) compare consultant diagnosis with final diagnosis and follow-up diagnosis. Methods We retrospectively reviewed 856 intradepartmental consultation records obtained from May 2017 to March 2018. For cases of Barrett’s dysplasia in biopsy specimens, H&E-stained slides were re-reviewed and the corresponding clinical information was retrieved from the electronic medical record. Results Twenty intradepartmental consultation cases of Barrett’s dysplasia were identified (involving 2 females and 18 males, mean age 67.8 ± 8.6 years, ranging 50-81 years). The most frequent reasons for consultation were indefinite dysplasia (IND) vs LGD and LGD vs HGD. Half of the cases showed concordance between referring pathologist and consultant pathologist(s), while 10% of the case showed a major discrepancy (resulting in significant changes in patient management and/or prognosis) and 40% showed a minor discrepancy (resulting in no significant impact on patient management and/or prognosis). The final diagnoses were changed after consultation for cases with major discrepancy, while 60% of cases with minor discrepancy remained the original diagnoses. Conclusions Intradepartmental consultations are strongly recommended for the challenging cases of BE dysplasia, which can effectively prevent over- or underdiagnosis. For challenging cases such as IND vs LGD, two or more consultants are usually needed to reach an agreement.

scholarly journals Predictors of upgrade diagnosis after endoscopic resection of gastric low-grade dysplasia: Who can be recommended regular follow-up?

2017 ◽  
Vol 28 ◽  
pp. iii33-iii34
Author(s):  
Wook Kim Hyung ◽  
Hwan Kang Dae ◽  
Woong Choi Cheol ◽  
Jin Kim Su ◽  
Seok Nam Hyeong ◽  
...  
Keyword(s):  
Endoscopic Resection ◽  
Low Grade ◽  
Low Grade Dysplasia

scholarly journals Mutational load may predict risk of progression in patients with Barrett’s oesophagus and indefinite for dysplasia: a pilot study

2019 ◽  
Vol 6 (1) ◽  
pp. e000268 ◽  
Author(s):  
Arvind J Trindade ◽  
Matthew J McKinley ◽  
Mohammad Alshelleh ◽  
Gabriel Levi ◽  
Molly Stewart ◽  
...  
Keyword(s):  
Pilot Study ◽  
Risk Stratification ◽  
High Grade Dysplasia ◽  
Barrett’S Oesophagus ◽  
Low Grade ◽  
High Grade ◽  
Mutational Load ◽  
Barrett's Oesophagus ◽  
Risk Of Progression ◽  
Indefinite For Dysplasia

Background and aimsMutational load (ML) has been shown to help risk-stratify those that may progress from non-dysplastic Barrett’s oesophagus (BE) to dysplastic disease. Management of patients with BE and indefinite for dysplasia (BE-IND) is challenging and risk stratification tools are lacking. The aim of this pilot study is to evaluate the utility of ML for risk stratification in patients with BE-IND.MethodsThis is a single-centre, retrospective pilot study evaluating ML quantification in patients with BE-IND. Histology at follow-up endoscopy at least 1 year after the baseline endoscopy was used to determine if a patient progressed to low or high dysplasia. The ML levels were then compared among patients who progressed to dysplasia versus those who did not.ResultsThirty-five patients who met the inclusion criteria were identified, and seven met the exclusion criteria. Twenty-eight patients were analysed, of whom eight progressed to low-grade dysplasia (6) and high-grade dysplasia (2). Seven of these eight patients had some level of genomic instability detected in their IND biopsy (ML ≥0.5). Ten of the 20 (50%) who did not progress had no ML level. At an ML cut-off above 1.5, the risk of progression to high-grade dysplasia was 33% vs 0% (p=0.005), with a sensitivity of 100% and a specificity of 85%.ConclusionThese results indicate that ML may be able to risk-stratify progression to high-grade dysplasia in BE-IND. Larger studies are needed to confirm these findings.

scholarly journals DOP41 Low-grade dysplasia prognosis and predictive factors for advanced neoplasia progression in the 21st century: A large multi-centre retrospective cohort study

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S078-S079
Author(s):  
M Kabir ◽  
K Curtius ◽  
I Al-Bakir ◽  
J Hartono ◽  
M Johnson ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Endoscopic Resection ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Study Endpoint ◽  
Low Grade ◽  
Advanced Neoplasia ◽  
Low Grade Dysplasia

Abstract Background Recent advances in ulcerative colitis (UC) endoscopic surveillance such as high-definition imaging and greater chromoendoscopy (CE) use have led to an increase in detection and resection of visible dysplasia. An updated study of prognosis of low-grade dysplasia (LGD) is needed to address uncertainty as to the accuracy of progression rates based on historical studies. Methods This retrospective cohort study involved four UK IBD centres. Hospital and endoscopy pathology databases were searched between 1 January 2001 and 30 December 2018 to identify adult patients with UC who had their first LGD diagnosis diagnosed within the extent of colitis. Only patients followed up with at least one colonoscopy or colectomy by 30 August 2019 were included. The study endpoint was time to high-grade dysplasia (HGD) or cancer (CRC), i.e. advanced neoplasia (AN), or end of follow-up. Survival analyses were performed using Kaplan–Meier estimation and Cox proportional hazards (PH) models. Results In total, 460 patients met the inclusion criteria and were followed up for a median of 4.1 years (IQR 6), equating to 2,232 patient-years. A mean of 3.7 (range 0–17) subsequent colonoscopies was performed per patient. Seventy-seven per cent of patients had CE surveillance. Complete endoscopic resection was achieved in 94% and 64% of the polypoid and non-polypoid LGD, respectively. There was progression to AN in 88 cases (19%) during follow-up. There was no significant difference in AN progression between centres. Unresectable non-polypoid or invisible LGD carried the greatest risk of AN development (Figure 1). On univariate Cox PH analysis, CE use was protective against AN progression (HR 0.5; 95% CI 0.3–1.0; p = 0.04). However, only highly significant predictors of LGD progression to AN on univariate analysis (Bonferroni adjusted p &lt; 0.003), were entered into the multivariate model: Cumulative risk of AN increased with the number of risk factors (Figure 2). Conclusion This is the largest study examining prognosis of LGD, based on endoscopic features, in this century. Five-year cumulative incidence of AN is low after complete endoscopic resection of visible LGD without surrounding dysplasia. Lesion size of 1 cm or more, invisibility, multifocality and unresectability of LGD are significant risk factors for progression to AN. These factors should be taken into consideration when discussing management options with patients.

scholarly journals Persistent indefinite for dysplasia in Barrett’s esophagus is a risk factor for dysplastic progression to low-grade dysplasia

2020 ◽  
Vol 33 (9) ◽  
Author(s):  
Andrew J Henn ◽  
Kevin Y Song ◽  
Amy A Gravely ◽  
Hector Mesa ◽  
Shahnaz Sultan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Risk Factor ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Smoking History ◽  
Low Grade ◽  
Indefinite For Dysplasia ◽  
Low Grade Dysplasia

Summary Patients with Barrett’s esophagus (BE) are at increased risk of esophageal adenocarcinoma (EAC). The risk is largely based on the degree of dysplasia. Dysplasia cannot always be differentiated from inflammatory changes, and therefore may be classified as indefinite for dysplasia (IND). The risk of progressive dysplasia in patients with IND is unclear. Our aim is to characterize the risk of progression in US veterans with BE-IND. We performed a single-center retrospective cohort study of patients with BE-IND between 2006 and 2016. All IND was diagnosed by consensus conference with an expert gastrointestinal (GI) pathologist or review by an expert GI pathologist and persistence was defined as IND present on subsequent endoscopic biopsy. The primary outcome was the incidence rate of high-grade dysplasia (HGD)/EAC. Secondary outcomes included any progression including incident low-grade dysplasia (LGD), any prevalent dysplasia and risk factors for dysplastic progression, namely persistent IND. Risk factors for progression were assessed using univariate and multivariate analysis with logistic regression. Among 107 patients with BE-IND, there were no incident cases of HGD/EAC. Twenty patients (18.7%) developed incident LGD during a median follow-up of 2.39 years (interquartile range, 1.13–5.17). The annual rate of progression to LGD was 5.95 per 100 patient-years (95% CI, 3.73–9.02). Prevalent dysplasia was common (9.3%). Eight patients had prevalent LGD, one patient had prevalent HGD and one patient had prevalent EAC. Twenty-eight patients (30.1%) were found to have persistent IND. Among those with persistent IND, 10 (36%) patients progressed to LGD (none to HGD/EAC). The progression rate to LGD for patients with persistent IND was 7.86 (95% CI, 3.99–14.02) cases per 100 patient-years versus 4.78 (95% CI, 2.48–8.52) for nonpersistent IND (P = 0.036). The odds ratio for progression to LGD in persistent IND was 3.06 (95% CI, 1.08–8.64). In multivariate analysis adjusting for age, smoking history, presence of hiatal hernia and BMI &gt; 30, persistent IND remained significant (OR 3.23; 95% CI, 1.04–9.98). Regression to nondysplastic BE was very common. Seventy-one (61%) patients developed complete and sustained regression of all dysplastic changes at last follow-up. Persistent IND, present in one-third of patients with IND, is an independent risk factor for progression to LGD. Although no patients in this cohort developed HGD/EAC, prevalent dysplasia was common (9.3%). Taken together, patients with IND should receive close surveillance for both prevalent and incident dysplasia especially if IND is persistent.

scholarly journals Intestinal anti-tissue transglutaminase IgA deposits as a complementary method for the diagnostic evaluation of celiac disease in patients with low-grade histological lesions

2021 ◽  
Author(s):  
María Roca ◽  
Ester Donat ◽  
Etna Masip ◽  
Verónica Ballester ◽  
Isabel Gómez ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Pediatric Population ◽  
Histological Study ◽  
Final Diagnosis ◽  
Low Grade ◽  
Positive Serology ◽  
Histological Lesion ◽  
Complementary Method

Summary Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2-3 lesion. 75 pediatric patients were split into 3 groups according to the final diagnosis: 1) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis;none presented intestinal anti-TG2 IgA deposits; 2) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in 7 and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and 3) 47 children with Marsh 2-3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.

scholarly journals Growth Differentiation Factor-15 in the Early Diagnosis and Risk Stratification of Patients with Acute Chest Pain

2012 ◽  
Vol 58 (2) ◽  
pp. 441-449 ◽  
Author(s):  
Nora Schaub ◽  
Tobias Reichlin ◽  
Raphael Twerenbold ◽  
Miriam Reiter ◽  
Stephan Steuer ◽  
...  
Keyword(s):  
Chest Pain ◽  
Early Diagnosis ◽  
Risk Stratification ◽  
Acute Chest Pain ◽  
Final Diagnosis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
All Cause Mortality ◽  
Integrated Discrimination Improvement

Abstract BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive marker that might aid in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction (AMI). METHODS In a prospective, international multicenter study, GDF-15, high-sensitivity cardiac troponin T (hs-cTnT), and B-type natriuretic peptide (BNP) were measured in 646 unselected patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. The primary prognostic end point was all-cause mortality during a median follow-up of 26 months. RESULTS AMI was the adjudicated final diagnosis in 115 patients (18%). GDF-15 concentrations at presentation were significantly higher in AMI patients compared to patients with other diagnoses. The diagnostic accuracy of GDF-15 at presentation for the diagnosis of AMI as quantified by the area under the ROC curve (AUC) was lower (AUC 0.69, 95% CI 0.64–0.74) compared to hs-cTnT (AUC 0.96, 95% CI 0.94–0.98, P &lt; 0.001) and BNP (AUC 0.74, 95% CI 0.69–0.80, P = 0.02). A total of 55 deaths occurred during follow-up. GDF-15 predicted all-cause mortality independently of and more accurately than hs-cTnT [AUC 0.85 (95% CI 0.81–0.90) vs 0.77 (95% CI 0.72–0.83), P = 0.002] and BNP (AUC 0.75, 95% CI 0.68–0.82, P = 0.007). Net reclassification improvement was 0.15 (P = 0.01), and the absolute integrated discrimination improvement was 0.07, yielding a relative integrated discrimination improvement of 0.36 (P = 0.07). CONCLUSIONS GDF-15 predicts all-cause mortality in unselected patients with acute chest pain independently of and more accurately than hs-cTnT and BNP. However, GDF-15 does not seem to help in the early diagnosis of AMI.

scholarly journals Markers of Plaque Instability in the Early Diagnosis and Risk Stratification of Acute Myocardial Infarction

2012 ◽  
Vol 58 (1) ◽  
pp. 246-256 ◽  
Author(s):  
Nora Schaub ◽  
Tobias Reichlin ◽  
Christophe Meune ◽  
Raphael Twerenbold ◽  
Philip Haaf ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Risk Stratification ◽  
Cardiac Troponin ◽  
Troponin T ◽  
Acute Chest Pain ◽  
High Sensitivity ◽  
Final Diagnosis ◽  
Cardiac Troponin T ◽  
Plaque Instability

Abstract BACKGROUND Plaque erosion and plaque rupture occur early in the pathophysiology of acute myocardial infarction (AMI). We hypothesized that markers of plaque instability might be useful in the early diagnosis and risk stratification of AMI. METHODS In this multicenter study, we examined 4 markers of plaque instability, myeloperoxidase (MPO), myeloid-related protein 8/14 (MRP-8/14), pregnancy-associated plasma protein-A (PAPP-A), and C-reactive protein (CRP) in 398 consecutive patients presenting to the emergency department with acute chest pain and compared them to normal and high-sensitivity cardiac troponin T (cTnT and hs-cTnT). The final diagnosis was adjudicated by 2 independent cardiologists. Primary prognostic end point was death during a median follow-up of 27 months. RESULTS The adjudicated final diagnosis was AMI in 76 patients (19%). At emergency department presentation, concentrations of all 4 biomarkers of plaque instability were significantly higher in patients with AMI than in patients with other diagnoses. However, their diagnostic accuracy as quantified by the area under the ROC curve (AUC) was low (MPO 0.63, MRP-8/14 0.65, PAPP-A 0.62, CRP 0.59) and inferior to both normal and high-sensitivity cardiac troponin T (cTnT 0.88, hs-cTnT 0.96; P &lt; 0.001 for all comparisons). Thirty-nine patients (10%) died during follow-up. Concentrations of MPO, MRP-8/14, and CRP were higher in nonsurvivors than in survivors and predicted all-cause mortality with moderate accuracy. CONCLUSIONS Biomarkers of plaque instability do not seem helpful in the early diagnosis of AMI but may provide some incremental value in the risk stratification of patients with acute chest pain.

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