Single-particle (molecule) tracking (SPT/SMT) is a powerful method to study dynamic processes in living cells at high spatial and temporal resolution. Even though SMT is becoming a widely used method ...in bacterial cell biology, there is no program employing different analytical tools for the quantitative evaluation of tracking data. We developed SMTracker, a MATLAB-based graphical user interface (GUI) for automatically quantifying, visualizing and managing SMT data via five interactive panels, allowing the user to interactively explore tracking data from several conditions, movies and cells on a track-by-track basis. Diffusion constants are calculated a) by a Gaussian mixture model (GMM) panel, analyzing the distribution of positional displacements in x- and y-direction using a multi-state diffusion model (e.g. DNA-bound vs. freely diffusing molecules), and inferring the diffusion constants and relative fraction of molecules in each state, or b) by square displacement analysis (SQD), using the cumulative probability distribution of square displacements to estimate the diffusion constants and relative fractions of up to three diffusive states, or c) through mean-squared displacement (MSD) analyses, allowing the discrimination between Brownian, sub- or superdiffusive behavior. A spatial distribution analysis (SDA) panel analyzes the subcellular localization of molecules, summarizing the localization of trajectories in 2D- heat maps. Using SMTracker, we show that the global transcriptional repressor AbrB performs highly dynamic binding throughout the Bacillus subtilis genome, with short dwell times that indicate high on/off rates in vivo. While about a third of AbrB molecules are in a DNA-bound state, 40% diffuse through the chromosome, and the remaining molecules freely diffuse through the cells. AbrB also forms one or two regions of high intensity binding on the nucleoids, similar to the global gene silencer H-NS in Escherichia coli, indicating that AbrB may also confer a structural function in genome organization.
Intestinal inflammation can impair mucosal healing, thereby establishing a vicious cycle leading to chronic inflammatory bowel disease (IBD). However, the signaling networks driving chronic ...inflammation remain unclear. Here we report that CD4⁺ T cells isolated from patients with IBD produce high levels of interleukin-22 binding protein (IL-22BP), the endogenous inhibitor of the tissue-protective cytokine IL-22. Using mouse models, we demonstrate that IBD development requires T cell-derived IL-22BP. Lastly, intestinal CD4⁺ T cells isolated from IBD patients responsive to treatment with antibodies against tumor necrosis factor-α (anti-TNF-α), the most effective known IBD therapy, exhibited reduced amounts of IL-22BP expression but still expressed IL-22. Our findings suggest that anti-TNF-α therapy may act at least in part by suppressing IL-22BP and point toward a more specific potential therapy for IBD.
Colonoscopy is a widely performed procedure with procedural volumes increasing annually throughout the world. Many procedures are now performed as part of colorectal cancer screening programmes. ...Colonoscopy should be of high quality and measures of this quality should be evidence based. New UK key performance indicators and quality assurance standards have been developed by a working group with consensus agreement on each standard reached. This paper reviews the scientific basis for each of the quality measures published in the UK standards.
Purpose
Anastomotic or stump leakage is a common and serious complication of colorectal surgery. The objective of this study was to retrospectively investigate the clinical use and potential benefit ...of transanal rinsing treatment (TRT) using an innovative rinsing catheter (RC) after treatment with endoscopic vacuum therapy (EVT).
Methods
Patients with leakage after low colorectal surgery who had been treated with EVT were retrospectively analyzed. A subset of patients was trained to perform TRT with a specially developed RC. We investigated the rate of complete healing of the leakage, septic complications, failure of the therapy, surgical revisions, ostomy closure rate, and complications related to endoscopic therapy.
Results
Between February 2007 and January 2014, 98 patients with local complications after low colorectal surgery, treated with EVT, were identified. Eighty-nine patients were analyzed (the treatment of nine patients was stopped due to medical or technical problems): 31 patients were treated with EVT only (EVT group) and 58 patients with EVT followed by TRT (EVT/TRT group). Complete healing of the leakage was significantly better in the EVT/TRT group 84% vs. 58% (
p
< 0.009), and significantly fewer septic complications needing surgical revision were detected 3% vs. 11% (
p
= 0.001). No significant differences regarding endoscopy-related complications and ostomy closure were found between EVT and EVT/TRT patients.
Conclusions
The use of patient-administered TRT with an innovative, customized RC after EVT is technically feasible and reliable and significantly improves therapeutic results. Further prospective trials with larger patient groups are needed to validate the results of our study.
PAIP 2019: Liver cancer segmentation challenge Kim, Yoo Jung; Jang, Hyungjoon; Lee, Kyoungbun ...
Medical image analysis,
January 2021, 2021-01-00, 20210101, Volume:
67
Journal Article
Peer reviewed
Open access
•The Pathology Artificial Intelligence Platform (PAIP) is a free research support platform.•The PAIP Liver Cancer Segmentation Challenge, Task 1 Liver Cancer Segmentation and Task 2 Viable Tumor ...Burden Estimation.•Most top-performing methods used deep convolutional networks (such as U-Net) with multi-scale ensemble methods.
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Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team’s algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation.
It is assumed that esophageal adenocarcinoma is the end result of a stepwise disease process that transitions through gastroesophageal reflux disease (GERD) and Barrett's esophagus. The aim of this ...study was to examine at what stage known risk factors exert their influence toward the progression to cancer.
We enrolled 113 consecutive outpatients without GERD, 188 with GERD, 162 with Barrett's esophagus, and 100 with esophageal adenocarcinoma or high-grade dysplasia (HGD). All patients underwent a standard upper endoscopy and completed a standardized questionnaire about their social history, symptoms, dietary habits, and prescribed medications. We used adjusted logistic regression analysis to assess risk factors between each two consecutive disease stages from the absence of reflux disease to esophageal adenocarcinoma.
Overall, male gender, smoking, increased body mass index (BMI), low fruit and vegetable intake, duration of reflux symptoms, and presence of a hiatal hernia were risk factors for cancer/HGD. However, different combinations of risk factors were associated with different disease stages. Hiatal hernia was the only risk factor to be strongly associated with the development of GERD. For GERD patients, male gender, age, an increased BMI, duration of reflux symptoms, and presence of a hiatal hernia were all associated with the development of Barrett's esophagus. Finally, the development of cancer/HGD among patients with Barrett's esophagus was associated with male gender, smoking, decreased fruit and vegetable intake, and a long segment of Barrett's esophagus, but not with age, BMI, or a hiatal hernia.
While some risk factors act predominantly on the initial development of reflux disease, others appear to be primarily responsible for the development of more advanced disease stages.
Summary
Background
The value of lower gastrointestinal endoscopy (LGIE; colonoscopy or sigmoidoscopy) relates to its ability to detect clinically relevant findings, predominantly cancers, ...preneoplastic polyps or inflammatory bowel disease. There are concerns that many LGIEs are performed on low‐risk patients with limited benefit.
Aims
To determine the diagnostic outcomes of LGIE for common symptoms.
Methods
We performed a cross‐sectional study of diagnostic LGIE between March 2019 and February 2020 using the UK National Endoscopy Database. We used mixed‐effects logistic regression models, incorporating random (endoscopist) and fixed (symptoms, patient age, and sex) effects upon two dependent variables (large polyp ≥10 mm and cancer diagnosis). Adjusted positive predictive values (aPPVs) were calculated.
Results
We analysed 384,510 LGIEs; 33.2% were performed on patients aged under 50 and 53.6% on women. Regarding colonoscopies, the unadjusted PPV for cancer was 1.5% (95% CI: 1.4–1.5); higher for men than women (1.9% vs. 1.1%, p < 0.01). The PPV for large polyps was 3.2% (95% CI: 3.1–3.2). The highest colonoscopy cancer aPPVs were in the over 50s (1.9%) and in those with rectal bleeding (2.5%) or anaemia (2.1%). Cancer aPPVs for other symptoms were <1% despite representing 54.3% of activity. In patients under 50, aPPVs were 0.4% for cancer and 1.6% for large polyps. Results were similar for sigmoidoscopy.
Conclusions
Most colonoscopies were performed on patients with low‐risk symptoms, where cancer risk was similar to the general population. Cancer and large polyp yield was highest in elderly patients with rectal bleeding or anaemia, although still fell short of FIT‐based screening yields.
The findings assist in identifying patient groups that would benefit from endoscopic assessment: it is clear that blood is the key ‐ either overt blood, or occult bleeding presenting as anaemia, or in the context of screening, abnormal faecal occult blood test. Our study also identifies those who could be appropriately triaged towards less urgent or even no investigation.
Outcomes of endoscopic surveillance after surgery for colorectal cancer (CRC) vary with the incidence and timing of CRC detection at anastomoses or non-anastomoses in the colorectum. We performed a ...systematic review and meta-analysis to evaluate the incidence of CRCs identified during surveillance colonoscopies of patients who have already undergone surgery for this cancer.
We searched PubMed, EMBASE, SCOPUS, and the Cochrane Central Register of Clinical Trials through January 1, 2018 to identify studies investigating rates of CRCs at anastomoses or other locations in the colorectum after curative surgery for primary CRC. We collected data from published randomized controlled, prospective, and retrospective cohort studies. Data were analyzed by multivariate meta-analytic models.
From 2373 citations, we selected 27 studies with data on 15,803 index CRCs for analysis (89% of patients with stage I–III CRC). Overall, 296 CRCs at non-anastomotic locations were reported over time periods of more than 16 years (cumulative incidence, 2.2% of CRCs; 95% confidence interval CI, 1.8%–2.9%). The risk of CRC at a non-anastomotic location was significantly reduced more than 36 months after resection compared with before this time point (odds ratio for non-anastomotic CRCs at 36–48 months vs 6–12 months after surgery, 0.61; 95% CI, 0.37–0.98; P = .031); 53.7% of all non-anastomotic CRCs were detected within 36 months of surgery. One hundred and fifty-eight CRCs were detected at anastomoses (cumulative incidence of 2.7%; 95% CI, 1.9%–3.9%). The risk of CRCs at anastomoses was significantly lower 24 months after resection than before (odds ratio for CRCs at anastomoses at 25–36 months after surgery vs 6–12 months, 0.56; 95% CI, 0.32–0.98; P = .036); 90.8% of all CRCs at anastomoses were detected within 36 months of surgery.
After surgery for CRC, the highest risk of CRCs at anastomoses and at other locations in the colorectum is highest during 36 months after surgery—risk decreases thereafter. Patients who have undergone CRC resection should be evaluated by colonoscopy more closely during this time period. Longer intervals may be considered thereafter.
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Background & Aims We investigated rates of detection of proximal serrated lesions in a cohort of average-risk patients undergoing screening colonoscopies. Methods We reviewed results from screening ...colonoscopies performed by attending gastroenterologists at 32 endoscopy centers from 2008–2010. Pathology slides were interpreted at the individual centers. For this analysis, serrated lesions included hyperplastic polyps larger than 10 mm, those interpreted as sessile serrated adenomas (or sessile serrated polyp), and traditional serrated adenomas. Rates of detection for conventional adenomas and serrated lesions were compared among centers. Results A total of 5778 lesions were detected in 7215 screening colonoscopies. Of the 5548 lesions with pathology results, 3008 (54.2%) were conventional adenomas, 350 (6.3%) were serrated, and 232 (4.2%) were proximal serrated. The proportion of colonoscopies with at least 1 proximal serrated lesion was 2.8% (range among centers, 0%–9.8%). The number of serrated lesions per colonoscopy ranged from 0.00–0.11 (average, 0.05 ± 0.25). Overall lesion detection rates correlated with proximal serrated lesion detection rates ( R = 0.91, P < .0001); conventional adenoma and proximal serrated lesion detection rates also correlated ( R = .43, P = .025). The detection rate of proximal serrated lesions differed significantly among centers ( P < .0001); odds ratios for detection ranged from 0–0.79. Some centers' pathologists never identified proximal serrated lesions as sessile serrated adenomas/polyps. Conclusions In an average-risk screening cohort, detection of proximal serrated lesions varied greatly among endoscopy centers. There was also substantial variation among pathologists in identification of sessile serrated adenomas/polyps. Nationally, a significant proportion of proximal serrated lesions may be missed during colonoscopy examination or incorrectly identified during pathology assessment. ClinicalTrials.gov Number: NCT00855348.
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