Upstart DNA sequencers could be a 'game changer'.

Increasing potential for fast, cheap genomes may break open biology's bottleneck and broaden clinical uses.

Patient-derived organoids for personalized gallbladder cancer modelling and drug screening.

BACKGROUND: Gallbladder carcinoma (GBC) is a relatively rare but highly aggressive cancer with late clinical detection and a poor prognosis. However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies. METHODS: We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole-exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC-101 and CUDC-907, were evaluated in vitro and in vivo. RESULTS: The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single-cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K/HDAC inhibitor CUDC-907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids. CONCLUSIONS: Patient-derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs.

Acceptability and Adequacy of a Non-endoscopic Cell Collection Device for Diagnosis of Barrett's Esophagus: Lessons Learned.

BACKGROUND: Endoscopic screening for Barrett's esophagus (BE) is common, costly, and underperformed in at-risk people. A non-endoscopic cell collection device can be used to collect esophageal cells, enabling BE screening. AIMS: This study assessed the acceptability and adequacy of a commercial non-endoscopic cell collection device in a US population. METHODS: Six sites enrolled patients with confirmed BE or heartburn/regurgitation for ≥ 6 months. Patients underwent administration of the device, consisting of a sponge encapsulated in a capsule. The capsule dwelled in the stomach for 7.5 min and was retracted via an attached suture. An adequate sample was ≥ 1 columnar cell by H&E staining. Sample quality was rated using a 0-5 scale, with 0 = no columnar cells and 5 = plentiful groups. Trefoil Factor 3 (TFF3) staining was performed. Accuracy was assessed using esophagogastroduodenoscopy (EGD)/biopsy as the gold standard. RESULTS: Of 191 patients, 99.5% successfully swallowed the device. Overall sample adequacy was 91% (171/188), with 84% (158/188) high quality. The detachment rate was 2/190 (1%). Overall sensitivity, specificity, and accuracy of the assay with TFF3 staining were 76%, 77%, and 76%. Sensitivity, specificity, and accuracy for ≥ 3 cm BE were 86%, 77%, and 82%. Asked if willing to repeat the procedure, 93% would, and 65% indicated a preference for the device over EGD. CONCLUSIONS: This study demonstrated a high rate of sample adequacy and promising acceptability of this non-endoscopic sampling device in a US population. Diagnostic characteristics suggest that non-endoscopic assessment of BE deserves further development as an alternative to endoscopy.

Cost-Effectiveness of a Serum Biomarker Test for Risk-Stratified Liver Ultrasound Screening for Hepatocellular Carcinoma.

OBJECTIVES: Risk-stratified ultrasound screening for hepatocellular carcinoma (HCC), informed by a serum biomarker test, enables resources to be targeted to patients at the highest risk of developing cancer. We aimed to investigate the cost-effectiveness of risk-stratified screening for HCC in the Australian healthcare system. METHODS: A Markov cohort model was constructed to test 3 scenarios for patients with compensated cirrhosis: (1) risk-stratified screening for high-risk patients, (2) all-inclusive screening, and (3) no formal screening. Probabilistic sensitivity analyses were undertaken to determine the impact of uncertainty. Scenario analyses were used to assess cost-effectiveness in Australia's Aboriginal and Torres Strait Islander peoples and to determine the impact of including productivity-related costs of mortality. RESULTS: Both risk-stratified screening and all-inclusive screening programs were cost-effective compared with no formal screening, with incremental cost-effectiveness ratios of A$39 045 and A$23 090 per quality-adjusted life-year (QALY), respectively. All-inclusive screening had an incremental cost-effectiveness ratio of A$4453 compared with risk-stratified screening and had the highest probability of being cost-effective at a willingness-to-pay (WTP) threshold of A$50 000 per QALY. Risk-stratified screening had the highest likelihood of cost-effectiveness when the WTP was between A$25 000 and A$35 000 per QALY. Cost-effectiveness results were further strengthened when applied to an Aboriginal and Torres Strait Islander cohort and when productivity costs were included. CONCLUSIONS: Cirrhosis population-wide screening for HCC is likely to be cost-effective in Australia. Risk-stratified screening using a serum biomarker test may be cost-effective at lower WTP thresholds.

Research Progress of Autofluorescence Imaging Technology in the Diagnosis of Early Gastrointestinal Tumors.

Early diagnosis and early treatment of gastrointestinal tumors are helpful to improve the prognosis of patients. Endoscopy is the best method for the diagnosis of early gastrointestinal tumors, but some early flat tumors may be missed under conventional white-light endoscopy. In order to improve the accuracy of endoscopic diagnosis of gastrointestinal tumors, especially early flat tumors, endoscopic autofluorescence imaging (AFI) as a new technique has been widely used in clinics in recent years. This article reviews the progress of the clinical application of AFI in the diagnosis of various gastrointestinal tumors.

Use of Silicon Nanowire Sensors for Early Cancer Diagnosis.

The review covers some research conducted in the field of medical and biomedical application of devices based on silicon sensor elements (Si-NW-sensors). The use of Si-NW-sensors is one of the key methods used in a whole range of healthcare fields. Their biomedical use is among the most important ones as they offer opportunities for early diagnosis of oncological pathologies, for monitoring the prescribed therapy and for improving the people's quality of life.

A Fully Automated and Integrated Microfluidic System for Efficient CTC Detection and Its Application in Hepatocellular Carcinoma Screening and Prognosis.

Analysis of circulating tumor cells (CTCs) is regarded as a useful diagnostic index to monitor tumor development and guide precision medicine. Although the immunoassay is a common strategy for CTC identification and heterogeneity characterization, it is challenged by poor reaction efficiency and laborious manipulations in microdevices, which hinder the sensitivity, throughput, simplification, and applicability. To meet the need for rapid, sensitive, and simple CTC analysis, we developed an efficient CTC detection system by integrating a 3D printed off-chip multisource reagent platform, a bubble retainer, and a single CTC capture microchip, which can achieve CTC capture and identification within 90 min. Compared with traditional CTC identification methods, this system decreases immunostaining time and antibody consumption by 90% and performs the on-chip immunoassay in a fully automated manner. Using this system, CTCs from the peripheral blood of 19 patients with various cancers were captured, detected, and compared with clinical data. The system shows great potential for early screening, real-time monitoring, and precision medicine for hepatocellular carcinoma (HCC). With the advantages of automation, stability, economy, and user-friendly operation, the proposed system is promising for clinical scenarios.

The concordance in lesion detection and characteristics between the Anatomical Intelligence and conventional breast ultrasound Scan method.

BACKGROUND: The aim of this study was to investigate the concordance in lesion detection, between conventional Handhold Ultrasound (HHUS) and The Anatomical Intelligence for Breast ultrasound scan method. RESULT: The AI-breast showed the absolute agreement between the resident and an experienced breast radiologist. The ICC for the scan time, number, clockface location, distance to the nipple, largest diameter and mean diameter of the lesion obtained by a resident and an experienced breast radiologist were 0.7642, 0.7692, 0.8651, 0.8436, 0.7502, 0.8885, respectively. The ICC of the both practitioners of AI-breast were 0.7971, 0.7843, 0.9283, 0.8748, 0.7248, 0.8163, respectively. The k value of Anatomical Intelligence breast between experienced breast radiologist and resident in these image characteristics of boundary, morphology, aspect ratio, internal echo, and BI-RADS assessment were 0.7424, 0.7217, 0.6741, 0.6419, 0.6241, respectively. The k value of the two readers of AI-breast were 0.6531, 0.6762, 0.6439, 0.6137, 0.5981, respectively. CONCLUSION: The anatomical intelligent breast US scanning method has excellent reproducibility in recording the lesion location and the distance from the nipple, which may be utilized in the lesions surveillance in the future.

Single-molecule amplification-free multiplexed detection of circulating microRNA cancer biomarkers from serum.

MicroRNAs (miRNAs) play essential roles in post-transcriptional gene expression and are also found freely circulating in bodily fluids such as blood. Dysregulated miRNA signatures have been associated with many diseases including cancer, and miRNA profiling from liquid biopsies offers a promising strategy for cancer diagnosis, prognosis and monitoring. Here, we develop size-encoded molecular probes that can be used for simultaneous electro-optical nanopore sensing of miRNAs, allowing for ultrasensitive, sequence-specific and multiplexed detection directly in unprocessed human serum, in sample volumes as small as 0.1 µl. We show that this approach allows for femtomolar sensitivity and single-base mismatch selectivity. We demonstrate the ability to simultaneously monitor miRNAs (miR-141-3p and miR-375-3p) from prostate cancer patients with active disease and in remission. This technology can pave the way for next generation of minimally invasive diagnostic and companion diagnostic tests for cancer.

A point-of-care chemiluminescence immunoassay for pepsinogen I enables large-scale community health screening.

Pepsinogen I (PGI) can reflect the morphology and function of the gastric mucosa. Accordingly, the large-scale community health screening of PGI can dramatically increase the early diagnosis rate of gastric cancer. However, PGI testing can only be carried out in comprehensive hospitals and health examination centers. To ameliorate this issue, a point-of-care chemiluminescent immunoassay for PGI was developed in a fully automated miniaturized instrument. This instrument was especially developed for health check-ups in the grassroots communities; its volume of which is only 0.18 m3. Critically, the entire detection process for a single sample only requires 20 min, and the samples can be loaded continuously, making the method suitable for high-throughput analysis. The assay displayed an excellent detection limit of 0.048 ng/mL with a broad detection range of 0-200 ng/mL. Furthermore, this assay exhibited high sensitivity and specificity, had low intra- and inter-assay coefficients of variation (<10%), and was not affected after storage at 37 °C for 7 days. The assay was used to detect PGI in 95 clinical serum samples, and the results were highly correlated with those that were clinically tested (correlation coefficient, R2 = 0.998). Hence, the method established in this work has great application value and can be broadly applied for the large-scale screening of gastric cancer in resource-limited areas.

Women's attitudes to the use of AI image readers: a case study from a national breast screening programme.

BACKGROUND: Researchers and developers are evaluating the use of mammogram readers that use artificial intelligence (AI) in clinical settings. OBJECTIVES: This study examines the attitudes of women, both current and future users of breast screening, towards the use of AI in mammogram reading. METHODS: We used a cross-sectional, mixed methods study design with data from the survey responses and focus groups. We researched in four National Health Service hospitals in England. There we approached female workers over the age of 18 years and their immediate friends and family. We collected 4096 responses. RESULTS: Through descriptive statistical analysis, we learnt that women of screening age (≥50 years) were less likely than women under screening age to use technology apps for healthcare advice (likelihood ratio=0.85, 95% CI 0.82 to 0.89, p<0.001). They were also less likely than women under screening age to agree that AI can have a positive effect on society (likelihood ratio=0.89, 95% CI 0.84 to 0.95, p<0.001). However, they were more likely to feel positive about AI used to read mammograms (likelihood ratio=1.09, 95% CI 1.02 to 1.17, p=0.009). DISCUSSION AND CONCLUSIONS: Women of screening age are ready to accept the use of AI in breast screening but are less likely to use other AI-based health applications. A large number of women are undecided, or had mixed views, about the use of AI generally and they remain to be convinced that it can be trusted.

Seizing the Means of Reproduction? Canada, Cancer Screening, and the Colonial History of the Cytopipette.

In recent years, self-sampling has emerged as a compelling way of increasing cervical cancer screening rates within First Nations, Inuit and Métis communities. By allowing women to take their own samples in private, when and where they are most comfortable, home testing kits have been framed as a new, unequivocally feminist technology, and a panacea in Indigenous health. But are these techniques really as ethical and empowering as they have been made out to be? To answer this question, this article traces the history of the uptake and use of cervical cancer screening technologies in Canada. By tracing the mechanics and motivations of two state-sponsored cervical cancer screening studies carried out by Canada's Department of Indian Health Services during the mid to late twentieth century, this piece explores the settler-colonial roots of cancer surveillance, and shows how the implementation of both Pap-testing and DIY forms of screening within Indigenous communities has, at least historically, been more about enacting biopolitical regimes than promoting feminist ideals or improving health outcomes.

Electrochemical biosensors for measurement of colorectal cancer biomarkers.

Colorectal cancer (CRC) is associated with one of the highest rates of mortality among cancers worldwide. The early detection and management of CRC is imperative. Biomarkers play an important role in CRC screening tests, CRC treatment, and prognosis and clinical management; thus rapid and sensitive detection of biomarkers is helpful for early detection of CRC. In recent years, electrochemical biosensors for detecting CRC biomarkers have been widely investigated. In this review, different electrochemical detection methods for CRC biomarkers including immunosensors, aptasensors, and genosensors are summarized. Further, representative examples are provided that demonstrate the advantages of electrochemical sensors modified by various nanomaterials. Finally, the limitations and prospects of biomarkers and electrochemical sensors in detection are also discussed. Graphical abstract.

Use of bioimpedance spectroscopy for prospective surveillance and early diagnosis of breast cancer-related lymphedema.

BACKGROUND: Bioimpedance spectroscopy has been suggested as a useful tool for early diagnosis of breast cancer-related lymphedema (BCRL). We aimed to describe the outcomes of published studies that evaluated bioimpedance analysis as a method for prospective surveillance and early diagnosis of BCRL. METHODS: We queried the PubMed, Ovid Medline, and EMBASE databases to identify studies that evaluated use of bioimpedance spectroscopy as a diagnostic tool. We used the keywords "bioimpedance" AND ("lymphedema" OR "lymphoedema") in the search. Only English-language studies that reported quantitative outcomes for patients with BCRL were included. RESULTS: Of 152, 235 and 116 identified articles in PubMed, Ovid Medline and EMBASE databases, only 22 were included. Use of bioimpedance analysis for prospective surveillance has been shown to prevent chronic BCRL. All the cross-sectional and retrospective studies that evaluated bioimpedance for diagnosis of BCRL reported significantly different L-Dex scores between lymphedema patients and healthy participants; in addition, bioimpedance scores were positively correlated with volume of lymphedema. CONCLUSION: Bioimpedance analysis is a potential tool with demonstrated benefits for prevention of chronic BCRL and may be an economic and great alternative for early diagnosis of BCRL.

AI-based smartphone apps for risk assessment of skin cancer need more evaluation and better regulation.

Smartphone applications ("apps") with artificial intelligence (AI) algorithms are increasingly used in healthcare. Widespread adoption of these apps must be supported by a robust evidence-base and app manufacturers' claims appropriately regulated. Current CE marking assessment processes inadequately protect the public against the risks created by using smartphone diagnostic apps.

An origami paper-based nanoformulated immunosensor detects picograms of VEGF-C per milliliter of blood.

Detecting vascular endothelial growth factor C (VEGF-C), a kind of tumor biomarker, is of significant clinical importance in evaluating the prognosis of patients with cancer. However, laboratory analyses are usually not suitable for point-of-care testing because they are expensive and time consuming. In response to these challenges, we fabricated an origami paper-based microfluidic electrochemical device. To improve the specificity of VEGF-C detection, nanocomposites, synthesized by new methylene blue (NMB), amino-functional single-walled carbon nanotubes (NH2-SWCNTs), and gold nanoparticles (AuNPs), were used to modify the surface of working electrodes. Results of electrochemical detection showed that the immunosensor had excellent linearity, ranging from 0.01 to 100 ng mL-1 (R2 = 0.988), and the limit of detection was 10 pg mL-1. To confirm the high specificity of the device under real-world conditions, we evaluated the device using clinical serum samples from our hospital. The results demonstrated that the device had an excellent performance and could provide a platform for real-time detection of cancers.

Diagnostic accuracy of tomosynthesis-guided vacuum assisted breast biopsy of ultrasound occult lesions.

This study aims to evaluate the diagnostic accuracy of digital breast tomosynthesis-guided vacuum assisted breast biopsy (DBT-VABB) of screening detected suspicious mammographic abnormalities comprising of calcifications, asymmetric densities, architectural distortions and spiculated masses. In this institutionally approved study, a total of 170 (n = 170) DBT-VABB were performed, 153 (90%) were for calcifications, 8 (4.7%) for spiculated mass, 5 (2.9%) for asymmetric density and 4 (2.4%) for architectural distortion. All these lesions were not detected on the corresponding ultrasound. Histopathology results revealed 140 (82.4%) benign, 9 (5.3%) borderline and 21 (12.4%) malignant lesions. The total upgrade rate at surgery was 40% for atypical ductal hyperplasia and 5.9% for ductal carcinoma in-situ. 3.6% discordant benign lesions showed no upgrade. DBT-VABB showed 100% specificity, 91.3% sensitivity and 100% positive predictive value (PPV) for detecting malignant lesions. The negative predictive value (NPV) was 80%. 2 (1.2%) patients had mild complications and 1 (0.6%) had severe pain. Our study showed that DBT-VABB was a safe and reliable method, with high sensitivity, specificity, PPV and NPV in the diagnosis of non-palpable benign and malignant breast lesions. Our data also confirmed the accuracy of DBT-VABB in detecting malignant lesions and we suggest further surgical excision in borderline lesions for a more accurate diagnostic evaluation.

Improving Utilization of Lung Cancer Screening Through Incorporating a Video-Based Educational Tool Into Smoking Cessation Counseling.

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) reduces lung cancer mortality in high-risk patients, but most of those eligible are not referred for screening, and most eligible smokers are not aware of LCS. Smoking cessation counseling may be an opportune time to educate smokers about LCS. Here we investigate the effect of LCS educational information on LDCT utilization and smoking cessation in LCS-eligible patients receiving smoking cessation counseling. PATIENTS AND METHODS: We randomized 1281 smokers aged 55-80 who underwent smoking cessation services to view a web-based educational video about LCS (n = 1026) or to receive usual care (n = 255). Outcomes included the utilization of chest computed tomographic (CT) scan during 6 months of follow-up, responses to survey questions, and patient-reported abstinence from smoking at 6 months. RESULTS: One hundred forty-six participants (14%) watched the video. Overall, 87 participants (8.5%) in the intervention group underwent any chest CT and 37 (3.6%) underwent LDCT compared to 22 (8.6%) and 11 (4.3%) in the control group during the 6-month follow-up period (P = .94 and .59, respectively). Among participants who completed watching the video, 27 (18.5%) underwent any chest CT and 13 (8.9%) underwent LDCT, compared to 22 (8.6%) and 11 (4.3%) in controls during follow-up (P = .0037 and .062, respectively). There was no difference in abstinence from smoking between groups. CONCLUSION: An LCS educational intervention may be effective in improving utilization of LDCT in eligible individuals who currently smoke at the time of smoking cessation counseling. Further research on the effect of LCS education in the context of smoking cessation counseling is needed.

A systematic review of handheld tools in lieu of colposcopy for cervical neoplasia and female genital schistosomiasis.

BACKGROUND: Visualization of the lesions in the lower genital tract is the mainstay for diagnosis of the four lesions found in female genital schistosomiasis (FGS), but colposcopes are generally not available in low-resource settings. OBJECTIVE: We sought to review handheld devices that could potentially be used for FGS diagnosis. SEARCH STRATEGY: We searched Medline and Embase 2015-2019 for handheld devices used in cervical cancer screening and FGS diagnosis. SELECTION CRITERIA: We excluded studies that did not compare the device to standard-of-care colposcopes or histopathology. MAIN RESULTS AND CONCLUSION: In 11 studies, four handheld colposcopes, two smartphones, and one compact digital camera were evaluated. Two handheld colposcopes were found to be potentially adequate for FGS diagnosis, namely Gynocular and Mobile ODT. The smartphones and digital camera did not have sufficient magnification to diagnose grainy sandy patches, one of the FGS lesion types. Customized software should be made to support the diagnosis of both FGS and cervical neoplasia. Real-time postgraduate training and quality control should be considered in future studies of handheld colposcopes. For patients from schistosomiasis endemic areas, we recommend that handheld devices are used for FGS. Studies are needed to determine which of the two devices is most adequate for FGS diagnosis in schistosomiasis endemic areas.

Lung Cancer Screening by Low-Dose Computed Tomography: Part 2 - Key Elements for Programmatic Implementation of Lung Cancer Screening.

PURPOSE: For screening with low-dose CT (LDCT) to be effective, the benefits must outweigh the potential risks. In large lung cancer screening studies, a mortality reduction of approx. 20 % has been reported, which requires several organizational elements to be achieved in practice. MATERIALS AND METHODS: The elements to be set up are an effective invitation strategy, uniform and quality-assured assessment criteria, and computer-assisted evaluation tools resulting in a nodule management algorithm to assign each nodule the needed workup intensity. For patients with confirmed lung cancer, immediate counseling and guideline-compliant treatment in tightly integrated regional expert centers with expert skills are required. First, pulmonology contacts as well as CT facilities should be available in the participant's neighborhood. IT infrastructure, linkage to clinical cancer registries, quality management as well as epidemiologic surveillance are also required. RESULTS: An effective organization of screening will result in an articulated structure of both widely distributed pulmonology offices as the participants' primary contacts and CT facilities as well as central expert facilities for supervision of screening activities, individual clarification of suspicious findings, and treatment of proven cancer. CONCLUSION: In order to ensure that the benefits of screening more than outweigh the potential harms and that it will be accepted by the public, a tightly organized structure is needed to ensure wide availability of pulmonologists as first contacts and CT facilities with expert skills and high-level equipment concentrated in central facilities. KEY POINTS: · For lung cancer screening, elements must function optimally and be tightly organized.. · Lung cancer screening requires a network of expert centers and collaborating facilities.. · IT infrastructure, QM, epidemiological surveillance, and linkage to cancer registries are essential.. CITATION FORMAT: · Delorme S, Kaaks R: Lung Cancer Screening by Low-Dose Computed Tomography: Part 2 - Key Elements for Programmatic Implementation of Lung Cancer Screening. Fortschr Röntgenstr 2021; 193: 644 - 651.