Dataset Information

Biopsy strategies for endoscopic screening of pre-malignant gastric lesions.

ABSTRACT: Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) were adopted to evaluate gastric risk stratification in five biopsy samples. This study aimed to evaluate the degree of gastric atrophy (GA) and intestinal metaplasia (IM) in five locations to detect a more representative biopsy sample in gastric cancer (GC) screening. Our study enrolled 368 patients and 5 biopsy pieces were acquired from them. Gastric risk stratification was calculated by OLGA and OLGIM staging system. The results revealed that the IM score in the incisura angularis was higher than that in the larger and lesser curvature of corpus mucosa (p?=?0.037 and p?=?0.030, respectively) and the IM score in the lesser curvature of antrum mucosa was higher than that in the incisura angularis mucosa (p?=?0.018). IM is more frequently observed in the angulus region than in the lesser curvature of corpus in the mild degree (p?=?0.004) and mild IM lesions in the lesser curvature of antrum were more frequently observed than in the incisura angularis mucosa (p?=?0.004), Four biopsy pieces protocol (larger curvature and lesser curvature of the antrum, lesser curvature of the corpus and angulus) demonstrated accurate consistency (97.83% and 98.37%, respectively) with a Kendall's tau-b of higher than 0.990, along with low misdiagnosis rates of OLGA and OLGIM (III?+?IV) (9.76% and 5.00%, respectively). Three biopsy pieces protocol (lesser curvature of the antrum and corpus, angulus biopsy) in OLGA and OLGIM staging system was close to the standard protocol (five biopsy specimens) with a consistency of 94.84% and 94.29% and has a Kendall's tau-b higher than 0.950 and diagnostic omission rates of 9.76% and 5.00%, respectively, which was exactly the same with the four biopsy pieces protocol. Furthermore, it had the second-highest Youden index (0.902 and 0.950, respectively) and area under the ROC curve (0.992 and 0.996, respectively) for the screening of high-risk GC by OLGA and OLGIM stages. Thus, we recommended the angulus and the lesser curvature of antrum as a conventional biopsy and three biopsy pieces for further GC risk screening.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6797776 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Biopsy strategies for endoscopic screening of pre-malignant gastric lesions.

Zhang Meng M Liu Shan S Hu Yue Y Bao Hai-Biao HB Meng Li-Na LN Wang Xiao-Teng XT Xu Yi Y Zhao Jing J Lu Bin B

Scientific reports 20191017 1

Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) were adopted to evaluate gastric risk stratification in five biopsy samples. This study aimed to evaluate the degree of gastric atrophy (GA) and intestinal metaplasia (IM) in five locations to detect a more representative biopsy sample in gastric cancer (GC) screening. Our study enrolled 368 patients and 5 biopsy pieces were acquired from them. Gastric risk stratification was calc ...[more]

PMID: 31624309

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Project description:Rationale: Cancer phosphoproteomics can provide insights regarding kinases that can be targeted for therapeutic applications. Monitoring the phosphoproteomics in cancer is expected to play a key role in optimizing treatments with kinase inhibitors. Clinical phosphoproteomics in surgical tissues and patient-derived models has been studied intensively. However, the reported data may not accurately reflect the phosphosignaling status in patients due to the effect of ischemia occurring during surgery or changes in the characteristics of cancer cells when establishing the models. In contrast, endoscopic biopsies have an advantage for clinical phosphoproteomics because they can be rapidly cryo-preserved. We aimed to develop a highly sensitive method for phosphoproteomics in endoscopic biopsies of gastric cancer. Methods: Three tumor biopsies and three normal gastric biopsies were obtained by endoscopy at one time, and subjected to our optimized phosphoproteomics. Phosphopeptides were enriched with an immobilized metal affinity chromatography, and labeled with Tandem Mass Tag reagent. Quantified phosphosites were compared between the pairs of tumor/normal biopsies within same patient. Cancer-specific activated pathways and kinases were identified by pathway enrichment analysis and kinase-substrate enrichment analysis. Results: Our protocol enabled the identification of more than 10,000 class 1 phosphosites from endoscopic biopsies. A comparison between samples from cancer tissue and normal mucosa demonstrated differences in the phosphosignaling, including biomarkers of response to DNA damage. Finally, cancer-specific activation of DNA damage response signaling was validated by additional phosphoproteomics of other patients and western blotting of gastric cancer/normal cells. Conclusion: In summary, our pioneering approach will facilitate more accurate clinical phosphoproteomics in endoscopic biopsies, which can be applied to monitor the activities of therapeutic kinases and, ultimately, can be a useful tool to precision medicine.

Project description:Background and study aims Traditionally in the case of a vascular interposition, endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has been contraindicated. A transvascular route (TV) is feasible and probably a safe alternative approach in selected patients, but data are scarce. The primary aim of this study was to analyze the diagnostic yield and safety of EUS-TV-FNA in thoracic and abdominal lesions. Secondary aims included evaluation of the clinical impact and technical aspects. Patients and methods A retrospective multicenter study was conducted with inclusion of all consecutive patients that underwent EUS-TV-FNA from July 2007 to January 2020. Feasibility, cytopathology, procedure details, and safety were evaluated. Univariate analysis was performed to identify variables associated with incidents, cytopathological diagnosis, and clinical impact. Results Data were collected from a total of 49 cases and 50 EUS-TV-FNAs. The aorta (n = 19) and portal system (n = 17) were the most frequently punctured. The most frequent lesions were mediastinal lymph nodes (n = 13) and pancreatic tumors (n = 11). The diagnostic yield was 86 %, and there were nondiagnostic samples in seven cases. Overall sensitivity, specificity, and accuracy were 88 % (95 %CI,0.74-0.96), 100 % (95 %CI,0.59-1), and 90 % (95 %CI,0.78-0.96), respectively. Only three incidents were detected: two mural hematomas and a self-limited bleeding of gastroduodenal artery. In most patients, there was a significant impact on clinical management (88 %). Arterial vessel and ASA-III had a trend with incidents (both, P < 0.08). Rapid on-site evlauation was found to be an independent predictor for obtaining a conclusive sample (OR 6.2; 95 %CI, 1.06-36.73, P < 0.04). Conclusions EUS-TV-FNA is feasible, seems to be safe, and can be recommended when no other targets are available, and the information obtained would impact on the clinical plan.

Project description:BACKGROUND:Systematic cancer screening has led to the increased detection of pre-malignant lesions (PMLs). The absence of reliable prognostic markers has led mostly to over treatment resulting in potentially unnecessary stress, or insufficient treatment and avoidable progression. Importantly, most mutational profiling studies have relied on PML synchronous to invasive cancer, or performed in patients without outcome information, hence limiting their utility for biomarker discovery. The limitations in comprehensive mutational profiling of PMLs are in large part due to the significant technical and methodological challenges: most PML specimens are small, fixed in formalin and paraffin embedded (FFPE) and lack matching normal DNA. METHODS:Using test DNA from a highly degraded FFPE specimen, multiple targeted sequencing approaches were evaluated, varying DNA input amount (3-200 ng), library preparation strategy (BE: Blunt-End, SS: Single-Strand, AT: A-Tailing) and target size (whole exome vs. cancer gene panel). Variants in high-input DNA from FFPE and mirrored frozen specimens were used for PML-specific variant calling training and testing, respectively. The resulting approach was applied to profile and compare multiple regions micro-dissected (mean area 5 mm2) from 3 breast ductal carcinoma in situ (DCIS). RESULTS:Using low-input FFPE DNA, BE and SS libraries resulted in 4.9 and 3.7 increase over AT libraries in the fraction of whole exome covered at 20x (BE:87%, SS:63%, AT:17%). Compared to high-confidence somatic mutations from frozen specimens, PML-specific variant filtering increased recall (BE:85%, SS:80%, AT:75%) and precision (BE:93%, SS:91%, AT:84%) to levels expected from sampling variation. Copy number alterations were consistent across all tested approaches and only impacted by the design of the capture probe-set. Applied to DNA extracted from 9 micro-dissected regions (8 PML, 1 normal epithelium), the approach achieved comparable performance, illustrated the data adequacy to identify candidate driver events (GATA3 mutations, ERBB2 or FGFR1 gains, TP53 loss) and measure intra-lesion genetic heterogeneity. CONCLUSION:Alternate experimental and analytical strategies increased the accuracy of DNA sequencing from archived micro-dissected PML regions, supporting the deeper molecular characterization of early cancer lesions and achieving a critical milestone in the development of biology-informed prognostic markers and precision chemo-prevention strategies.

Project description:ImportanceThe rapidly increasing number of gastric cancer examinations performed over a short period might influence screening performance. Accessing the association between calendar month and gastric cancer detection rates might improve policy and guide institutional support.ObjectiveTo evaluate the association between the increased number of examinations over a certain period and gastric cancer detection rates among a large population included in the Korean National Cancer Screening Program (KNCSP).Design, setting, and participantsThis retrospective, population-based cohort study used data from the KNCSP comprising 26 765 665 men and women aged 40 years or older who participated in the screening program between January 1, 2013, and December 31, 2016. Data were analyzed from November 1, 2019, to March 31, 2020.ExposuresGastric cancer screening with endoscopy.Main outcomes and measuresThe primary outcome was monthly gastric cancer detection rates in the KNCSP. A negative binomial regression model was used to evaluate the association between the screening month and detection rates.ResultsIn total, 21 535 222 individuals underwent endoscopy (mean [SD] age, 55.61 [10.61] years; 11 761 709 women [54.62%]). The quarterly number of participants was the highest in the last quarter of the study period (2013-2014: 4 094 951 [41.39%], 2015-2016: 4 911 629 [42.19%]); this proportion was 2.48 to 2.84 times greater than that of the first quarter. Cancer detection rates were the lowest in December (2013-2014: 0.22; 95% CI, 0.22-0.23; 2015-2016: 0.21; 95% CI, 0.21-0.22); this was approximately a 40.0% to 45.0% reduction compared with the rates in January. The age group was the significant factor for monthly detection rates. After adjustment for the age group and taking account of the number of screenings, the estimated coefficient range for the screening month was negative and the detection rate in December was significantly different than in January for both the consequent cycles (2013-2014: -0.05 to -0.18; P < .001; and 2015-2016: -0.06 to -0.19; P < .001). In the multivariable logistic model, the association of calendar month with detected cancer remained after adjusting for other confounding factors (December, 2013-2014: odds ratio, 0.82; 95% CI, 0.76-0.87; P < .001; 2015-2016: odds ratio, 0.83; 95% CI, 0.79-0.89; P < .001).Conclusions and relevanceThe findings of this cohort study suggest that the workload of endoscopists increased with the increasing number of examinations toward the end of the year, as demonstrated by the decreased cancer detection rates. These findings may help to improve gastric cancer detection rates of screening programs by controlling the monthly screening number and policy modifications.

Dataset Information

Biopsy strategies for endoscopic screening of pre-malignant gastric lesions.

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Biopsy strategies for endoscopic screening of pre-malignant gastric lesions.

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