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Introduction Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease.Methods and analysis A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course.Ethics and dissemination The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal.Study registration NL8231—10 December 2019; Netherlands Trial Register.

Background and study aims Fujifilm has developed a novel ELUXEO 7000 endoscope system that employs light-emitting diodes (LEDs) at four different wavelengths as light sources that enable blue light imaging (BLI), linked color imaging (LCI), and high-definition white-light endoscopy (HD-WLE). The aim of this study was to address the diagnostic accuracy of real-time polyp characterization using BLI, LCI and HD-WLE (ELUXEO 7000 endoscopy system). Patients methods This is a prespecified post-hoc analysis of a prospective study in which 22 experienced endoscopists (> 2,000 colonoscopies) from eight international centers participated. Using a combination of BLI, LCI, and HD-WLE, lesions were endoscopically characterized including a high- or low-confidence statement. Per protocol, digital images were created from all three imaging modalities. Histopathology was the reference standard. Endoscopists were familiar with polyp characterization, but did not take dedicated training for purposes of this study. Results Overall, 341 lesions were detected in 332 patients. Of the lesions, 269 histologically confirmed polyps with an optical diagnosis were included for analysis (165 adenomas, 27 sessile serrated lesions, and 77 hyperplastic polyps). Overall, polyp characterization was performed with high confidence in 82.9 %. The overall accuracy for polyp characterization was 75.1 % (95 % confidence interval [CI] 69.5–80.1 %), compared with an accuracy of 78.0 % (95 % CI 72.0–83.2 %) for high confidence assignments. The accuracy for endoscopic characterization for diminutive polyps was 74.7 % (95 %CI 68.4–80.3 %), compared with an accuracy of 78.2 % (95 % CI 71.4–84.0 %) for high-confidence assignments. Conclusions The diagnostic accuracy of BLI, LCI, and HD-WLE by experienced endoscopist for real-time polyp characterization seems limited (NCT03344289).

Colorectal carcinoma (CRC) is a common cancer and the second most common cause of death. The therapeutic costs for this disease will continue to rise due to an increasing incidence and the introduction of new chemotherapeutic modalities. Colorectal carcinoma is preceded by precursor lesions, which can be used as a target for early detection and therapy. Biennial population screening with faecal occult blood tests (FOBT) lowers CRC mortality with 14–18%. Five year screening with flexible sigmoidoscopy is a cost-effective alternative, which yields a higher preventive effect when similar participation rates are achieved. Screening colonoscopy has the advantage of examination of the complete colon but disadvantages are the high participant burden and the higher demand for endoscopic personnel and endoscopy units. Future screening modalities like faecal DNA markers and CT colonography are promising but need further improvement. In Europe, faecal occult blood testing and flexible sigmoidoscopy are currently the most suitable screening modalities for colorectal cancer screening.

Background: Non-invasive biomarkers may reduce post-colonoscopy colorectal cancer (CRC) rates and colonoscopy overuse in Lynch syndrome. Unlike faecal immunochemical test (FIT), faecal volatile organic compounds (VOCs) may accurately detect both advanced and non-advanced colorectal neoplasia., Aim: The aim of this study was to evaluate the potential of faecal VOCs-separately and with FIT-to guide optimal colonoscopy intervals in Lynch syndrome., Methods: Prospective longitudinal multicentre study in which individuals with Lynch syndrome collected faeces before and after high-quality surveillance colonoscopy. VOC-patterns were analysed using field asymmetric ion mobility spectrometry (FAIMS) and gas chromatography-ion mobility spectrometry (GC-IMS) followed by machine learning pipelines, and combined with FIT at 2.55 μg Hb/g faeces. Gas chromatography time-of-flight mass spectrometry analysed individual VOC abundance., Results: Among 200 included individuals (57% female, median 51 years), 62 had relevant neoplasia at colonoscopy: 3 CRC, 6 advanced adenoma (AA), 3 advanced serrated lesion (ASL), and 50 non-advanced adenoma (NAA). Respective sensitivity and negative predictive value for CRC and AA (and also ASL in case of FAIMS) were 100% and 100% using FAIMS (54% specificity), and 89% and 99% using GC-IMS (58% specificity). Respective sensitivity and specificity for any relevant neoplasia were 88% and 44% (FAIMS) and 84% and 28% (GC-IMS); accuracy did not significantly improve upon VOC-FIT. VOC-patterns differed before and after polypectomy (AUC 0.70). NAA showed decreased faecal abundance of butanal, 2-oxohexane, dimethyldisulphide and dimethyltrisulphide., Conclusions: In Lynch syndrome, faecal VOCs may be a promising strategy for postponing colonoscopy and for follow-up after polypectomy. Our results serve as a stepping stone for large validation studies., Trial Registration: NL8749., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

BACKGROUND : Accurate polyp size measurement is important for polyp risk stratification and decision-making regarding polypectomy and surveillance. Recently, a virtual scale (VS) function has been developed that allows polyp size measurement through projection of an adaptive VS onto colorectal polyps during real-time endoscopy. We aimed to evaluate the VS in terms of variability and systematic differences. METHODS : We conducted a video-based study with 120 colorectal polyps, measured by eight dedicated colorectal gastroenterologists (experts) and nine gastroenterology residents following endoscopy training (trainees). Three endoscopic measurement methods were compared: (1) visual, (2) snare and (3) VS measurement. We evaluated the method-specific variance (as measure of variability) in polyp size measurements and systematic differences between these methods. RESULTS : Variance in polyp size measurements was significantly lower for VS measurements compared to visual and snare measurements for both experts (0.52 vs. 1.59 and 1.96, p < 0.001) and trainees (0.59 vs. 2.21 and 2.53, p < 0.001). VS measurement resulted in a higher percentage of polyps assigned to the same size category by all endoscopists compared to visual and snare measurements (experts: 69 % vs. 55 % and 59 %; trainees: 67 % vs. 51 % and 47 %) and reduced the maximum difference between individual endoscopists regarding the percentage of polyps assigned to the ≥ 10 mm size category (experts: 1.7 % vs. 10.0 % and 5.0 %; trainees: 2.5 % vs. 6.7 % and 11.7 %). Systematic differences between methods were < 0.5 mm. CONCLUSIONS : Use of the VS leads to lower polyp size measurement variability and more uniform polyp sizing by individual endoscopists compared to visual and snare measurements., Competing Interests: H. Beaumont has received speaker fees from Medtronic. B. Bastiaansen has received speaker fees from Olympus, Tillotts Pharma AG, and Ovesco Endoscopy AG. D. Ramsoekh has received a research grant from AbbVie (outside the submitted work) and served as a member of the Data Safety Monitoring Board of Vivoryon Therapeutics. P. Fockens has received research support from Boston Scientific and a consulting fee from Olympus and Cook Endoscopy. E. Dekker received a research grant from Fujifilm, honoraria for consultancy from Olympus, Fujifilm, Ambu, InterVenn, Norgine, and Exact Sciences and speakers' fees from Olympus, GI Supply, Norgine, IPSEN/Mayoly, FujiFilm and Steris. The remaining authors declare that they have no conflict of interest., (This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background We aimed to compare the accuracy of the optical diagnosis of diminutive colorectal polyps, including sessile serrated lesions (SSLs), between a computer-aided diagnosis (CADx) system and endoscopists during real-time colonoscopy. Methods We developed the POLyp Artificial Recognition (POLAR) system, which was capable of performing real-time characterization of diminutive colorectal polyps. For pretraining, the Microsoft-COCO dataset with over 300 000 nonpolyp object images was used. For training, eight hospitals prospectively collected 2637 annotated images from 1339 polyps (i. e. publicly available online POLAR database). For clinical validation, POLAR was tested during colonoscopy in patients with a positive fecal immunochemical test (FIT), and compared with the performance of 20 endoscopists from eight hospitals. Endoscopists were blinded to the POLAR output. Primary outcome was the comparison of accuracy of the optical diagnosis of diminutive colorectal polyps between POLAR and endoscopists (neoplastic [adenomas and SSLs] versus non-neoplastic [hyperplastic polyps]). Histopathology served as the reference standard. Results During clinical validation, 423 diminutive polyps detected in 194 FIT-positive individuals were included for analysis (300 adenomas, 41 SSLs, 82 hyperplastic polyps). POLAR distinguished neoplastic from non-neoplastic lesions with 79 % accuracy, 89 % sensitivity, and 38 % specificity. The endoscopists achieved 83 % accuracy, 92 % sensitivity, and 44 % specificity. The optical diagnosis accuracy between POLAR and endoscopists was not significantly different (P = 0.10). The proportion of polyps in which POLAR was able to provide an optical diagnosis was 98 % (i. e. success rate). Conclusions We developed a CADx system that differentiated neoplastic from non-neoplastic diminutive polyps during endoscopy, with an accuracy comparable to that of screening endoscopists and near-perfect success rate. [ABSTRACT FROM AUTHOR]

Assessment of the anatomical colorectal segment of polyps during colonoscopy is important for treatment and follow-up strategies, but is largely operator dependent. This feasibility study aimed to assess whether, using images of a magnetic endoscope imaging (MEI) positioning device, a deep learning approach can be useful to objectively divide the colorectum into anatomical segments. Models based on the VGG-16 based convolutional neural network architecture were developed to classify the colorectum into anatomical segments. These models were pre-trained on ImageNet data and further trained using prospectively collected data of the POLAR study in which endoscopists were using MEI (3930 still images and 90,151 video frames). Five-fold cross validation with multiple runs was used to evaluate the overall diagnostic accuracies of the models for colorectal segment classification (divided into a 5-class and 2-class colorectal segment division). The colorectal segment assignment by endoscopists was used as the reference standard. For the 5-class colorectal segment division, the best performing model correctly classified the colorectal segment in 753 of the 1196 polyps, corresponding to an overall accuracy of 63%, sensitivity of 63%, specificity of 89% and kappa of 0.47. For the 2-class colorectal segment division, 1112 of the 1196 polyps were correctly classified, corresponding to an accuracy of 93%, sensitivity of 93%, specificity of 90% and kappa of 0.82. The diagnostic performance of a deep learning approach for colorectal segment classification based on images of a MEI device is yet suboptimal (clinicaltrials.gov: NCT03822390). [ABSTRACT FROM AUTHOR]

A recent study published in the journal Endoscopy examined the use of a non-invasive faecal immunochemical test (FIT) to detect colorectal neoplasia in individuals with Lynch syndrome. The study found that a FIT threshold of 4.08 μg/g may be a safe strategy to postpone colonoscopy in approximately 9 out of 10 individuals with Lynch syndrome. The study suggests that larger validation studies should be conducted to further explore this approach. [Extracted from the article]

Colorectal carcinoma (CRC) is a common cancer and the second most common cause of death. The therapeutic costs for this disease will continue to rise due to an increasing incidence and the introduction of new chemotherapeutic modalities. Colorectal carcinoma is preceded by precursor lesions, which can be used as a target for early detection and therapy. Biennial population screening with faecal occult blood tests (FOBT) lowers CRC mortality with 14–18%. Five year screening with flexible sigmoidoscopy is a cost-effective alternative, which yields a higher preventive effect when similar participation rates are achieved. Screening colonoscopy has the advantage of examination of the complete colon but disadvantages are the high participant burden and the higher demand for endoscopic personnel and endoscopy units. Future screening modalities like faecal DNA markers and CT colonography are promising but need further improvement. In Europe, faecal occult blood testing and flexible sigmoidoscopy are currently the most suitable screening modalities for colorectal cancer screening. [ABSTRACT FROM AUTHOR]

Due to the worldwide increasing incidence of colorectal cancer, more and more focus is shifting towards methods for the early detection of polyps in the colon. In this work, we present a technique and a design to use dielectric spectroscopy with microwaves to assist in the early detection of colorectal cancer. A flexible, tubular design with six different segments was manufactured on a thin polyimide substrate. This design can be slid over an endoscope and used as a cap-assisted endoscopic attachment. Three different complementary split ring resonators were implemented into this design. When the design is deployed, the segments expand such that the sensors directly contact the colon tissue, even for varying colon diameters. The sensor behavior proved to be stable at different dilation levels and a sensitivity of up to 20.6 MHz per a.u. of permittivity was achieved over a broad permittivity range. Additionally, frequency multiplexing of different sensors was implemented to increase the sensor count while restricting the number of interconnections. Furthermore, several biological tissue samples, with a close resemblance to colorectal tissue, were measured with this design and were correctly identified. At last, a low-cost measurement implementation, that tracks the insertion loss of the sensors, was proposed to replace the expensive microwave lab equipment and a strong correlation was achieved between both measurement setups. [ABSTRACT FROM AUTHOR]

This article discusses a prospective multicentre study that aimed to determine if non-invasive faecal volatile organic compounds (VOCs) could be used to detect colorectal neoplasia in individuals with Lynch syndrome. The study involved collecting faecal samples from individuals prior to surveillance colonoscopy and analyzing them using field asymmetric ion mobility spectrometry (FAIMS) and machine learning techniques. The results showed that faecal VOC patterns had a high sensitivity and moderate specificity for detecting relevant neoplasia in Lynch syndrome. The study suggests that faecal VOCs could potentially be used as a diagnostic test for personalized colonoscopy surveillance in Lynch syndrome. [Extracted from the article]

This article, published in the journal Endoscopy, discusses the use of a virtual scale (VS) function for measuring the size of colorectal polyps during colonoscopy. The study compared the VS measurements to other measurement methods and evaluated the clinical feasibility of the VS. The results showed that the variability in polyp size measurements was significantly lower for VS measurements compared to visual and snare-aided measurements. The use of the VS led to more uniform polyp sizing and no clinically relevant systematic differences were identified. However, it should be noted that the VS measurement is not feasible for all polyps. [Extracted from the article]

Introduction: Benign liver tumours and cysts (BLTCs) comprise a heterogeneous group of cystic and solid lesions, including hepatic haemangioma, focal nodular hyperplasia and hepatocellular adenoma. Some BLTCs, for example, (large) hepatocellular adenoma, are at risk of complications. Incidence of malignant degeneration or haemorrhage is low in most other BLTCs. Nevertheless, the diagnosis BLTC may carry a substantial burden and patients may be symptomatic, necessitating treatment. The indications for interventions remain matter of debate. The primary study aim is to investigate patient-reported outcomes (PROs) of patients with BLTCs, with special regards to the influence of invasive treatment as compared with the natural course of the disease., Methods and Analysis: A nationwide observational cohort study of patients with BLTC will be performed between October 2021 and October 2026, the minimal follow-up will be 2 years. During surveillance, a questionnaire regarding symptoms and their impact will be sent to participants on a biannual basis and more often in case of invasive intervention. The questionnaire was previously developed based on PROs considered relevant to patients with BLTCs and their caregivers. Most questionnaires will be administered by computerised adaptive testing through the Patient-Reported Outcomes Measurement Information System. Data, such as treatment outcomes, will be extracted from electronic patient files. Multivariable analysis will be performed to identify patient and tumour characteristics associated with significant improvement in PROs or a complicated postoperative course., Ethics and Dissemination: The study was assessed by the Medical Ethics Committee of the University Medical Center Groningen and the Amsterdam UMC. Local consultants will provide information and informed consent will be asked of all patients. Results will be published in a peer-reviewed journal., Study Registration: NL8231-10 December 2019; Netherlands Trial Register., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Advanced endoscopic resection techniques for complex colorectal polyps have evolved significantly over the past decade, leading to a management shift from surgical to endoscopic resection as the preferred treatment. However, in practice, interhospital consultation and appropriate referral management remain challenging, leading to unnecessary surgical resections. To support regional care for patients with complex colorectal polyps, facilitate peer consultations, and lower thresholds for referrals, an expert panel consultation platform was initiated in the northwestern region of the Netherlands., Methods: We initiated a regional expert panel in the northwestern region of the Netherlands for patients with complex colorectal polyps and studied the implementation, adaption, and clinical impact. All panel consultations between June 2019 and May 2021 were retrospectively analyzed, and user satisfaction among panel members was evaluated., Results: Eighty-eight patients with complex colorectal polyps from 11 of 15 participating centers (73.3%) were discussed in our panel. The most common reason for panel consultation was suspicion of invasive cancer in 36.4% (n = 32). After panel consultation, 43.2% of the consulting endoscopists (n = 38) changed their initial treatment strategy, and in 63.6% (n = 56) patients were referred to another endoscopy center. Of 26 cases submitted with a primary proposal for surgical treatment, surgery was avoided in 7 (26.9%). User satisfaction was rated high in most participating centers (91.7%)., Conclusions: Our study shows that implementation of and consultation with a regional expert panel can be a valuable tool for endoscopists to guide and optimize treatment of complex colorectal polyps and facilitate interhospital referrals in a regional network., (Copyright © 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Optical spectroscopy and hyperspectral imaging have shown the potential to discriminate between cancerous and noncancerous tissue with high sensitivity and specificity. However, to date, these techniques have not been effectively translated to real-time endoscope platforms. Hyperspectral imaging of the fluorescence excitation spectrum represents new technology that may be well suited for endoscopic implementation. However, the feasibility of detecting differences between normal and cancerous mucosa using fluorescence excitation-scanning hyperspectral imaging has not been evaluated. The goal of this study was to evaluate the initial feasibility of using fluorescence excitation-scanning hyperspectral imaging for measuring changes in fluorescence excitation spectrum concurrent with colonic adenocarcinoma using a small pre-pilot-scale sample size. Ex vivo analysis was performed using resected pairs of colorectal adenocarcinoma and normal mucosa. Adenocarcinoma was confirmed by histologic evaluation of hematoxylin and eosin (H&E) permanent sections. Specimens were imaged using a custom hyperspectral imaging fluorescence excitation-scanning microscope system. Results demonstrated consistent spectral differences between normal and cancerous tissues over the fluorescence excitation range of 390 to 450 nm that could be the basis for wavelength-dependent detection of colorectal cancers. Hence, excitation-scanning hyperspectral imaging may offer an alternative approach for discriminating adenocarcinoma from surrounding normal colonic mucosa, but further studies will be required to evaluate the accuracy of this approach using a larger patient cohort. [ABSTRACT FROM AUTHOR]

Background: Lynch syndrome (or HNPCC) is a colorectal cancer syndrome caused by germline mutations in either one of the DNA mismatch repair (MMR) genes hMLH1, hMSH2, hMSH6 or hPMS2. Mutations in hMLH1 and hMSH2 are most prevalent. Here we aimed to determine the cancer risk of MMR gene mutation carriers and, in addition, the efficacy of colonoscopy surveillance in Chinese Lynch syndrome family members with and without MMR gene mutations. Methods: A Lynch syndrome family registry encompassing 106 families in Northern China was recently established. Detailed pedigree data for each family were collected and hMLH1 and hMSH2 gene mutation analyses were performed. Germ-line mutations were identified in probands from 42 of these families, and additional genetic analyses were performed in each member of these 42 families to identify mutation and non-mutation carriers. Among the family members included, 180 received colonoscopy and the remaining cases were followed without colonoscopy. Results: Overall 54.8 % of the Lynch syndrome family members carried MMR gene mutations, and these mutation carriers exhibited significantly higher colorectal cancer and other Lynch syndrome-associated cancer risks as compared to non-mutation carriers. The cumulative risk for all Lynch syndrome-related cancers at age 70 was 93.8 % for both hMLH1 and hMSH2 mutation carriers, and 81.7 % and 93.1 % for colorectal cancer at this age, respectively. Whereas 43 of 102 (42.2 %) mutation carriers exhibited significant colonoscopy findings, including 10 colorectal cancers, none of 78 non-mutation carriers exhibited significant findings, and no cancers were detected. In addition, in the mutation carriers, colonoscopy surveillance led to the detection of more early stage cancers than in the non-surveillance group (70.0 % versus 36.5 %, p < 0.01). Conclusion: In Lynch syndrome family members, we recommend pre-symptomatic MMR gene mutation analysis in order to identify high risk individuals for colonoscopy surveillance. [ABSTRACT FROM AUTHOR]

In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly. In fluorescence imaging, the difference between autofluorescence of cancer lesions compared to normal tissues were used in endoscopy to distinguish malignant lesions from normal tissue or inflammation and in determining the boarders of cancer lesions in surgery. Recent advances in drugs targeting specific tumor receptors, such as monoclonal antibodies (mAb), has created a new demand for developing non-invasive in vivo imaging techniques for detection of cancer biomarkers, and for monitoring their down regulations during therapy. Targeted treatments, combined with new imaging techniques, are expected to potentially result in new imaging and treatment paradigms in cancer therapy. Similar approaches can potentially be applied for the characterization of other disease-related biomarkers. In this chapter, we provide a review of diffuse optical and fluorescence imaging techniques with their application in functional brain imaging and cancer diagnosis. [ABSTRACT FROM AUTHOR]

In vivo optical imaging is being conducted in a variety of medical applications, including optical breast cancer imaging, functional brain imaging, endoscopy, exercise medicine, and monitoring the photodynamic therapy and progress of neoadjuvant chemotherapy. In the past three decades, in vivo diffuse optical breast cancer imaging has shown promising results in cancer detection, and monitoring the progress of neoadjuvant chemotherapy. The use of near infrared spectroscopy for functional brain imaging has been growing rapidly. In fluorescence imaging, the difference between autofluorescence of cancer lesions compared to normal tissues were used in endoscopy to distinguish malignant lesions from normal tissue or inflammation and in determining the boarders of cancer lesions in surgery. Recent advances in drugs targeting specific tumor receptors, such as AntiBodies (MAB), has created a new demand for developing non-invasive in vivo imaging techniques for detection of cancer biomarkers, and for monitoring their down regulations during therapy. Targeted treatments, combined with new imaging techniques, are expected to potentially result in new imaging and treatment paradigms in cancer therapy. Similar approaches can potentially be applied for the characterization of other disease-related biomarkers. In this chapter, we provide a review of diffuse optical and fluorescence imaging techniques with their application in functional brain imaging and cancer diagnosis. [ABSTRACT FROM AUTHOR]

Background: Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy. Methods: A case-control study was performed to determine the prognostic value of DNA ploidy and p53 in IBD-related neoplasia. Cases with IBD-related colorectal cancer (CRC), detected in our surveillance program between 1985-2008, were selected and matched with two controls, for age, gender, disease characteristics, interval of follow-up, PSC, and previous surgery. Biopsies were assessed for DNA ploidy, p53, grade of inflammation and neoplasia. Progression to neoplasia was analyzed with Cox regression analysis, adjusting for potentially confounding variables. Results: Adjusting for age, we found statistically significant Hazard ratios (HR) between development of CRC, and low grade dysplasia (HR5.5; 95%CI 2.6-11.5), abnormal DNA ploidy (DNA index (DI) 1.06-1.34, HR4.7; 95%CI 2.9-7.8 and DI>1.34, HR6.6; 95%CI 3.7-11.7) and p53 immunopositivity (HR3.0; 95%CI 1.9-4.7) over time. When adjusting for all confounders, abnormal DNA ploidy (DI 1.06-1.34, HR4.7; 95%CI 2.7-7.9 and DI>1.34, HR5.0; 95%CI 2.5-10.0) and p53 immunopositivity (HR1.7; 95%CI 1.0-3.1) remained statistically significant predictive of neoplasia. Conclusion: In longstanding IBD, abnormal DNA ploidy and p53 immunopositivity are important risk factors of developing CRC. The yield of surveillance may potentially increase by adding these biomarkers to the routine assessment of biopsies. [ABSTRACT FROM AUTHOR]

Background/aims: The identification of Lynch syndrome is hampered by the absence of specific diagnostic features and underutilisation of genetic testing. Prediction models have therefore been developed, but they have not been validated for a clinical genetic setting. The aim of the present study was to evaluate the usefulness of currently available prediction models. Methods: The authors collected data of 321 index probands who were referred to the department of clinical genetics of the Erasmus Medical Center because of a family history of colorectal cancer. These data were used as input for five previously published models. External validity was assessed by discriminative ability (AUC: area under the receiver operating characteristic curve) and calibration. For further insight, predicted probabilities were categorised with cut-offs of 5%, 10%, 20% and 40%. Furthermore, costs of different testing strategies were related to the number of extra detected mutation carriers. Results: Of the 321 index probands, 66 harboured a germline mutation. All models discriminated well between high risk and low risk index probands (AUC 0.82-0.84). Calibration was well for the Premm1,2 and Edinburgh model, but poor for the other models. Cut-offs could be found for the prediction models where costs could be saved while missing only few mutations. Conclusions: The Edinburgh and Premm1,2 model were the models with the best performance for an intermediate to high risk setting. These models may well be of use in clinical practice to select patients for further testing of mismatch repair gene mutations. [ABSTRACT FROM AUTHOR]

Background and aims: In Lynch syndrome, the clinical phenotype in MSH6 mutation families differs from that in MLHI and MSH2 families. Therefore, MSH6 mutation families are less likely to fulfil diagnostic criteria such as the Amsterdam II criteria (AC II) and the revised Bethesda guidelines (rBG), and will be underdiagnosed. The aim of the present study was to evaluate the contribution of MSH6 gene mutations in families that were analysed for Lynch syndrome in a diagnostic setting. Methods: Families that had molecular analysis for Lynch syndrome were included in this study. Complete molecular screening of the MLH1, MSH2 and MSH6 genes was performed in all families. Microsatellite instability (MSI) and immunohistochemical (IHC) analysis was performed in almost all families. Clinical data were collected from medical records and family pedigrees. Results: A total of 108 families were included. MSI and IRC analysis was performed in 97 families, and in 40 an MSI-high phenotype with absent protein expression was found. Germline mutation analysis detected mutations in 23 families (7 MLHJ, 4 MSH2 and 12 MSH6). The majority of MSH6 families were AC II negative, but fulfilled the rBG. Conclusions: There is a high incidence of MSH6 mutations in families tested for Lynch syndrome in a diagnostic setting. Many of these families remain underdiagnosed using the AC II. The rBG are more useful to select these families for further analysis. However, to optimise the detection of MSH6 families, MSI and IHC analysis should also be performed in families with clustering of late-onset endometrial carcinoma. [ABSTRACT FROM AUTHOR]

Background The most common hereditary colorectal cancer syndrome is hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome. Diagnosis of this syndrome is difficult, because of lack of specific diagnostic fatures. Aim To discuss the diagnostic criteria and laboratory work up for HNPCC. Furthermore, survelillance programs for HNPCC and treatment of HNPCC associated colorectal cancer are discussed. Results Current diagnostic criteria, including the Amsterdam II and Bethesda criteria, are suboptimal for the detection of HNPCC. Molecular screening by microsatellite instability (MSI) and immunohistochemistry (IHC) is useful in the diagnosis of HNPCC. Both techniques have a higher sensitivity compared to the Amsterdam II and Bethesda criteria. A combination of both MSI and IHC provides the most optimal selection for mutation analysis. After identification of a mutation in an affected individual, genetic counselling and presymptomatic mutation analysis should be offered to relatives. Furthermore, colonoscopic surveillance should be performed in proven mutation carriers. Conclusions Identification of HNPCC is a clinical challenge involving many clinicians. Identification of persons at risk can be achieved by a combination of a detailed family history, testing with molecular and mutation analysis. [ABSTRACT FROM AUTHOR]

This study evaluated the use of genetic testing and time trends in hereditary non-polyposis colorectal cancer (HNPCC), (attenuated) familial adenomatous polyposis [(A)FAP] and human MutY homolog ( MUTYH) associated polyposis (MAP) families. Eighty-seven families, who were diagnosed with disease-causing mutations between 1995 and 2006, were included in this study. The families consisted of 1547 individuals at risk. Data of these individuals were collected from medical records and family pedigrees. There was considerable interest in genetic testing with test rates of 41% in HNPCC families, 42% in (A)FAP families and 53% in MAP families. The use of genetic testing was associated with age and parenthood. Despite the interest in genetic testing, many risk carriers do not apply for testing. Moreover, time trend analysis showed a decline in test rate in HNPCC families. Studies evaluating the reasons for not testing are needed. Furthermore, a better implementation of genetic testing in clinical practice is desirable. [ABSTRACT FROM AUTHOR]

The paper uses the two methods suggested in both the ICNIRP and proposed IEEE safety guidelines for compliance testing of security systems based on time-varying magnetic fields being introduced for electronic article surveillance (EAS), radiofrequency identification, and other applications. For nonsinusoidal pulses that are often used, the two procedures are to treat the exposure as a multifrequency exposure with various frequency components or to calculate the peak induced current densities or electric fields treating the highest of the pulses of duration t[sub p] as a single frequency, half sinusoid of the same duration and frequency 1/(2t[sub p]). Using either of the procedures, the induced current densities (J) or electric fields (E) are compared to the basic restrictions on J or E for compliance testing. Using a heterogeneous, tissue-classified anatomic model of the human body, we calculate the induced J and E for the various tissues for a realistic, EAS system for two typical nonsinusoidal pulses to show that the two methods give substantially different results. While the approximate hut simpler method of treating the pulse as a half sinusoid results in peak induced J or E that may be compliant with safety guidelines, the rigorous method of treating such exposures as multifrequency exposures gives induced current densities or electric fields that may be up to twice as large, thus making such systems potentially noncompliant with the safety guidelines. Since it is more accurate, it is suggested that safety assessment based on the Fourier analysis leading to multifrequency components be used for compliance testing of such devices. [ABSTRACT FROM AUTHOR]

Background: Recent guidelines recommend the Lynch Syndrome prediction models MMRPredict, MMRPro, and PREMM1,2,6 for the identification of MMR gene mutation carriers. We compared the predictive performance and clinical usefulness of these prediction models to identify mutation carriers., Methods: Pedigree data from CRC patients in 11 North American, European, and Australian cohorts (6 clinic- and 5 population-based sites) were used to calculate predicted probabilities of pathogenic MLH1, MSH2, or MSH6 gene mutations by each model and gene-specific predictions by MMRPro and PREMM1,2,6. We examined discrimination with area under the receiver operating characteristic curve (AUC), calibration with observed to expected (O/E) ratio, and clinical usefulness using decision curve analysis to select patients for further evaluation. All statistical tests were two-sided., Results: Mutations were detected in 539 of 2304 (23%) individuals from the clinic-based cohorts (237 MLH1, 251 MSH2, 51 MSH6) and 150 of 3451 (4.4%) individuals from the population-based cohorts (47 MLH1, 71 MSH2, 32 MSH6). Discrimination was similar for clinic- and population-based cohorts: AUCs of 0.76 vs 0.77 for MMRPredict, 0.82 vs 0.85 for MMRPro, and 0.85 vs 0.88 for PREMM1,2,6. For clinic- and population-based cohorts, O/E deviated from 1 for MMRPredict (0.38 and 0.31, respectively) and MMRPro (0.62 and 0.36) but were more satisfactory for PREMM1,2,6 (1.0 and 0.70). MMRPro or PREMM1,2,6 predictions were clinically useful at thresholds of 5% or greater and in particular at greater than 15%., Conclusions: MMRPro and PREMM1,2,6 can well be used to select CRC patients from genetics clinics or population-based settings for tumor and/or germline testing at a 5% or higher risk. If no MMR deficiency is detected and risk exceeds 15%, we suggest considering additional genetic etiologies for the cause of cancer in the family., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Gingiva is the soft tissue that surrounds and protects the teeth. Healthy gingiva provides an effective barrier to periodontal insults to deeper tissue, thus is an important indicator to a patient's periodontal health. Current methods in assessing gingival tissue health, including visual observation and physical examination with probing on the gingiva, are qualitative and subjective. They may become cumbersome when more complex cases are involved, such as variations in gingival biotypes where feature and thickness of the gingiva are considered. A noninvasive imaging technique providing depth‐resolved structural and vascular information is necessary for an improved assessment of gingival tissue and more accurate diagnosis of periodontal status. We propose a three‐dimensional (3D) imaging technique, optical coherence tomography (OCT), to perform in situ imaging on human gingiva. Ten volunteers (five male, five female, age 25‐35) were recruited; and the labial gingival tissues of upper incisors were scanned using the combined use of state‐of‐the‐art swept‐source OCT and OCT angiography (OCTA). Information was collected describing the 3D tissue microstructure and capillary vasculature of the gingiva within a penetration depth of up to 2 mm. Results indicate significant structural and vascular differences between the two extreme gingival biotypes (ie, thick and thin gingiva), and demonstrate special features of vascular arrangement and characteristics in gingival inflammation. Within the limit of this study, the OCT/OCTA technique is feasible in quantifying different attributes of gingival biotypes and the severity of gingival inflammation. This paper describes a depth‐resolved microscopy technique, namely optical coherence tomography (OCT), for in vivo imaging of human gingiva. The paper focuses on the three‐dimensional tomography of the gingiva at microresolution and how the gingival tissues (both structure and vasculature) emerge under OCT. The findings present differences in gingival tissues between different biotypes, and strong link between gingival vascularization and inflammation. Therefore, this imaging technique can serve as an important diagnostic tool for clinical assessment of the gingiva. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 62-year-old man presented with severe, continuous abdominal pain to a general hospital. He underwent an abdominal computed tomography (CT) scan and showed evidence of acute pancreatitis and despite appropriate treatment intense abdominal pain persisted. It indicates that skin rash, abdominal pain, and the multiple ulcerations in the esophagus and stomach raised clinical suspicion of varicella zoster virus (VZV) infection.