Detection Of Gastrointestinal Cancers Research Articles

Optical-resolution functional gastrointestinal photoacoustic endoscopy based on optical heterodyne detection of ultrasound

Photoacoustic endoscopy shows promise in the detection of gastrointestinal cancer, inflammation, and other lesions. High-resolution endoscopic imaging of the hemodynamic response necessitates a small-sized, high-sensitivity ultrasound sensor. Here, we utilize a laser ultrasound sensor to develop a miniaturized, optical-resolution photoacoustic endoscope. The sensor can boost the acoustic response by a gain factor of ωo/Ω (the frequency ratio of the signal light and measured ultrasound) by measuring the acoustically induced optical phase change. As a result, we achieve a noise-equivalent pressure density (NEPD) below 1.5 mPa·Hz-1/2 over the measured range of 5 to 25 MHz. The heterodyne phase detection using dual-frequency laser beams of the sensor can offer resistance to thermal drift and vibrational perturbations. The endoscope is used to in vivo image a rat rectum and visualize the oxygen saturation changes during acute inflammation, which can hardly be observed with other imaging modalities.

Robotic large‐area optical biopsy imaging for automated detection of gastrointestinal cancers tested in tissue phantoms and ex vivo porcine bowel

AbstractGastrointestinal endoscopy is a subjective procedure that frequently requires tissue samples for diagnosis. Contact optical biopsy (OB) techniques have the aim of providing direct diagnosis of endoscopic areas without excising tissue samples but lack the wide‐area coverage required for locating and resecting lesions. This article presents a large‐area robotically deployed OB imaging platform for endoscopic detection of colorectal cancer as an add‐on for conventional endoscopes. In vitro, in silicon colon phantoms, the platform achieves an optical resolution of 0.5 line pairs per millimeter, while resolving simulated cancer lesions down to 0.75 mm diameter across large‐area images (55‐103 cm2). Large‐area OB images were generated in an ex vivo porcine colon. The platform allows centimeter‐sized large‐area OB imaging in vitro and ex vivo with submillimeter resolution, including automatic data segmentation of simulated cancer areas. The ability for robotic actuation and spectrum collection is also shown for ex vivo animal colon. If successful, this technology could widen access to user‐independent high‐quality endoscopy and early detection of gastrointestinal cancers.

Риск-ориентированные подходы к эндоскопической диагностике рака ЖКТ в медицинских организациях первичного звена (на примере ГАУЗ СО ГБ № 1 г. Нижний Тагил)

Early detection of gastrointestinal cancer is an actual public health problem. The implementation of the modern endoscopic diagnostic methods based on the progressive digital technologies significantly reduce the risks of diagnostic errors and contributes to the effective solution of that problem. P u r p o s e : to clarify the possibilities of the early detection of gastrointestinal cancer by equipping the endoscopy unit of the city district hospital with the modern digital endoscopes, including devices with zoom functions – ZOOM. M a t e r i a l s a n d m e t h o d s . The article analyzes the statistical data of the work of the endoscopy unit of Nizniy Tagil State city hospital № 1 from 2013 to 2022 (except 2020–21, when the hospital was completely redesigned as a COVID-hospital). R e s u l t s . A clear relationship between the increase in the number of detected oncopathologies of the gastrointestinal tract and the modern technical equipment of the endoscopic units under the modernization of primary health care program in the Sverdlovsk region in 2021 is presented. Based on risk-based approaches and evidence-based medicine data, the importance expert-class equipment in the routine endoscopic practice in the primary healthcare district hospital for diagnosing gastrointestinal cancer at an early stage is shown. Modern approaches to optical endoscopic diagnostics are analyzed, as well as the potential risks of diagnostic errors associated with technical equipment and possible measures to reduce these risks for further improvement of primary endoscopic diagnostics aimed at detecting gastrointestinal cancer in the early stages are determined, the expediency of equipping endoscopic units of primary care medical organizations with endoscopes inreached magnification functions – ZOOM, as well as photo and video recording of digital images with the possibility of archiving, color printing and further expert analysis of endoscopic images. C o n s e q u e n c e . From the presented statistical data, it is clearly seen how with the improvement of the equipment quality, the detection of gastrointestinal cancer of various localizations is growing.

Clinical performance of a liquid biopsy test based on the detection of multiple DNA methylation biomarkers for early detection of gastrointestinal cancers.

e16096 Background: Gastrointestinal cancers (colorectal cancer, gastric cancer and esophageal cancer) are the most prevalent malignant tumors in China, resulting in 975,537 new cases and 958,675 deaths in 2020. Currently, the gold standard for the early detection of these cancers remains to be gastrointestinal endoscopy. However, the invasiveness, low throughput and high cost of these procedures have prevented its wide acceptance by Chinese population. The objective of this study was to develop a liquid biopsy test based on the detection of multiple DNA methylation biomarkers (SpecGastro test) and evaluate its clinical performance for early detection of gastrointestinal cancers. Methods: Two hundred and eighty-two gastrointestinal cancer patients (98 colorectal cancers, 136 gastric cancers and 48 esophageal cancers) and 195 control subjects were included. Ten milliliters of peripheral blood was drawn and 3.5 mL plasma was separated for cell-free DNA extraction and bisulfite conversion. The converted DNA was subsequently examined by SpecGastro test, a multiplex qPCR assay that detected six methylation biomarkers and one internal control. Results: Overall sensitivity for SpecGastro test was 76.6% (95% CI: 71.1-81.3%) with a specificity of 89.2% (95% CI: 83.8-93.1%). Sensitivities for colorectal cancer, gastric cancer and esophageal cancer were 87.8% (95% CI: 79.2-93.2%), 69.9% (95% CI: 61.3-77.3%) and 72.9% (95% CI: 57.9-84.3%), respectively. A high AUC of 0.903 (95% CI: 0.873-0.928) indicated that SpecGastro test distinguished gastrointestinal cancer patients from control subjects with high accuracy. Conclusions: Our analysis demonstrated the utility of SpecGastro test to detect three types of gastrointestinal cancers with high sensitivity and specificity. These results supported the feasibility of this blood-based SpecGastro test as a complementary tool to the existing single-cancer early detection tests.

Cell-free DNA liquid biopsy for early detection of gastrointestinal cancers: A systematic review.

BACKGROUNDGastrointestinal tumors are among the most common cancer types, and early detection is paramount to improve their management. Cell-free DNA (cfDNA) liquid biopsy raises significant hopes for non-invasive early detection.AIMTo describe current applications of this technology for gastrointestinal cancer detection and screening.METHODSA systematic review of the literature was performed across the PubMed database. Articles reporting the use of cfDNA liquid biopsy in the screening or diagnosis of gastrointestinal cancers were included in the analysis.RESULTSA total of 263 articles were screened for eligibility, of which 13 articles were included. Studies investigated colorectal cancer (5 studies), pancreatic cancer (2 studies), hepatocellular carcinoma (3 studies), and multi-cancer detection (3 studies), including gastric, oesophageal, or bile duct cancer, representing a total of 4824 patients. Test sensitivities ranged from 71% to 100%, and specificities ranged from 67.4% to 100%. Pre-cancerous lesions detection was less performant with a sensitivity of 16.9% and a 100% specificity in one study. Another study using a large biobank demonstrated a 94.9% sensitivity in detecting cancer up to 4 years before clinical symptoms, with a 61% accuracy in tissue-of-origin identification. CONCLUSIONcfDNA liquid biopsy seems capable of detecting gastrointestinal cancers at an early stage of development in a non-invasive and repeatable manner and screening simultaneously for multiple cancer types in a single blood sample. Further trials in clinically relevant settings are required to determine the exact place of this technology in gastrointestinal cancer screening and diagnosis strategies.

EpiPanGI Dx: A Cell-free DNA Methylation Fingerprint for the Early Detection of Gastrointestinal Cancers.

DNA methylation alterations have emerged as front-runners in cell-free DNA (cfDNA) biomarker development. However, much effort to date has focused on single cancers. In this context, gastrointestinal (GI) cancers constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers. Herein, we performed a genome-wide DNA methylation analysis of multiple GI cancers to develop a pan-GI diagnostic assay. By analyzing DNA methylation data from 1,781 tumor and adjacent normal tissues, we first identified differentially methylated regions (DMR) between individual GI cancers and adjacent normal, as well as across GI cancers. We next prioritized a list of 67,832 tissue DMRs by incorporating all significant DMRs across various GI cancers to design a custom, targeted bisulfite sequencing platform. We subsequently validated these tissue-specific DMRs in 300 cfDNA specimens and applied machine learning algorithms to develop three distinct categories of DMR panels RESULTS: We identified three distinct DMR panels: (i) cancer-specific biomarker panels with AUC values of 0.98 (colorectal cancer), 0.98 (hepatocellular carcinoma), 0.94 (esophageal squamous cell carcinoma), 0.90 (gastric cancer), 0.90 (esophageal adenocarcinoma), and 0.85 (pancreatic ductal adenocarcinoma); (ii) a pan-GI panel that detected all GI cancers with an AUC of 0.88; and (iii) a multi-cancer (tissue of origin) prediction panel, EpiPanGI Dx, with a prediction accuracy of 0.85-0.95 for most GI cancers. Using a novel biomarker discovery approach, we provide the first evidence for a cfDNA methylation assay that offers robust diagnostic accuracy for GI cancers.

Advances of Tumorigenesis, Diagnosis at Early Stage, and Cellular Immunotherapy in Gastrointestinal Malignancies.

Globally, in 2018, 4.8 million new patients have a diagnosis of gastrointestinal (GI) cancers, while 3.4 million people died of such disorders. GI malignancies are tightly relevant to 26% of the world-wide cancer incidence and occupies 35% of all cancer-associated deaths. In this article, we principally investigated molecular and cellular mechanisms of tumorigenesis in five major GI cancers occurring at esophagus, stomach, liver, pancreas, and colorectal region that illustrate high morbidity in Eastern and Western countries. Moreover, through this investigation, we not only emphasize importance of the tumor microenvironment in development and treatment of malignant tumors but also identify significance of M2PK, miRNAs, ctDNAs, circRNAs, and CTCs in early detection of GI cancers, as well as systematically evaluate contribution of personalized precision medicine including cellular immunotherapy, new antigen and vaccine therapy, and oncolytic virotherapy in treatment of GI cancers.

Microsatellite Instability in Gastrointestinal Cancer Using Deep Learning: A Review

Currently, the health management is a foremost concern all over the world. Particularly in India, due to lack of physical activity, overweight, stress and unhealthy eating habits, various diseases like heart disease, diabetes and cancer disease are increasing at a very rapid rate. The common problem which is affecting all age generation is a gastrointestinal disorder which includes various conditions like colitis, colon polyps, perianal infection and cancer. Microsatellite Instability (MSI) in gastrointestinal (GI) cancer is the second leading cause of death worldwide. However, this cancer can frequently be asymptomatic during the early stages and stay undetected until the later stages of tumor advancement. Deep Learning has the capacity to detect MSI in gastrointestinal cancer at an early stage, which is very helpful for the patients. There are number of research papers, focusing on different techniques used for detection of MSI in gastrointestinal caner. In this paper, we focus on the recent trends of deep learning methods in this field. The main goal of this review paper is to provide a detailed discussion from technological perspective. This article discusses various challenges, molecular subtypes, pathologist approach and computer aided approach for gastrointestinal cancer detection. Also, this article brings into light the existing literature and state of art with their contribution in different aspects of detection of microsatellite instability in gastrointestinal tract with the help of deep learning techniques.

Carbohydrate Antigen 50: Values for Diagnosis and Prognostic Prediction of Intrahepatic Cholangiocarcinoma.

Background and objectives: Cancer-associated carbohydrate antigen 50 (CA50) is a marker for detection of gastrointestinal cancers, especially of pancreatic and colon cancer. In this study, the power of CA50 as a diagnostic and prognostic marker was evaluated in intrahepatic cholangiocarcinoma (iCCA). Materials and Methods: Serum CA50 levels of iCCA patients and non-cholangiocarcinoma controls (non-CCA, including healthy persons and patients with benign biliary diseases and other gastrointestinal cancers) were measured using MAGLUMI®800 CLIA analyzer. Diagnostic and prognostic values of serum CA50 levels were evaluated. Results: CA50 levels in the sera of iCCA patients were significantly higher than those of non-CCA controls (p < 0.001, Mann–Whitney U test). Using cut-off value of 25 U/mL, CA50 provided 65.9% sensitivity, 87.3% specificity, and 80.1% accuracy for diagnosis of iCCA. Serum CA50 levels were increased and associated with the severity of bile duct pathology. In addition, a higher level of CA50 was associated with poor clinical outcome and shorter survival in iCCA patients. Multivariate survival analysis by Cox regression model revealed the potential of CA50 as an independent poor prognostic indicator for iCCA, regardless of the age, sex, histological types, or tumor stages. Conclusions: CA50 can be a diagnostic and poor prognostic marker candidate for iCCA.

Advances in optical gastrointestinal endoscopy: a technical review.

Optical endoscopy is the primary diagnostic and therapeutic tool for management of gastrointestinal (GI) malignancies. Most GI neoplasms arise from precancerous lesions; thus, technical innovations to improve detection and diagnosis of precancerous lesions and early cancers play a pivotal role in improving outcomes. Over the last few decades, the field of GI endoscopy has witnessed enormous and focused efforts to develop and translate accurate, user‐friendly, and minimally invasive optical imaging modalities. From a technical point of view, a wide range of novel optical techniques is now available to probe different aspects of light–tissue interaction at macroscopic and microscopic scales, complementing white light endoscopy. Most of these new modalities have been successfully validated and translated to routine clinical practice. Herein, we provide a technical review of the current status of existing and promising new optical endoscopic imaging technologies for GI cancer screening and surveillance. We summarize the underlying principles of light–tissue interaction, the imaging performance at different scales, and highlight what is known about clinical applicability and effectiveness. Furthermore, we discuss recent discovery and translation of novel molecular probes that have shown promise to augment endoscopists' ability to diagnose GI lesions with high specificity. We also review and discuss the role and potential clinical integration of artificial intelligence‐based algorithms to provide decision support in real time. Finally, we provide perspectives on future technology development and its potential to transform endoscopic GI cancer detection and diagnosis.

Abstract 1084: EpiPanGI-Dx: A cell-free DNA methylation fingerprint for the early detection of gastrointestinal cancers

Abstract Purpose: In view of high cancer-specificity, DNA methylation alterations have emerged as front-runners in biomarker development, especially as cell-free DNA (cf-DNA) biomarkers for early detection of cancer. However, much effort to date has focused on developing cancer type-specific biomarkers, but have not explored the possibility of developing a pan-cancer diagnostic assay. In this context, gastrointestinal (GI) cancers, including colorectal (CRC), esophageal squamous cell and adenocarcinoma (ESCC and EAC), gastric (GC), liver (HCC) and pancreatic ductal adenocarcinoma (PDAC) constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers. Here we undertook a genomewide DNA methylation analysis for multiple GI cancers, followed by development of a novel cf-DNA methylation biomarker panels for the early detection of GI cancers (EpiPanGI Dx). Experimental design: By analyzing the DNA methylation data from 1940 tumor and adjacent normal tissues from TCGA and GSE72872 datasets, we first identified the differentially methylated regions (DMRs) between individual GI cancers and adjacent normal tissues, as well as across all GI cancers. We next prioritized a list of DMRs encompassing a 25.6 Mb genomic region by incorporating all identified DMRs across various GI cancers to design a custom SeqCap Epi, targeted bisulfite sequencing platform, optimized for analysis of low-abundance cf-DNA derived from plasma specimens. Using this approach, we sequenced 300 plasma specimens from all GI cancers, as well as age-matched healthy controls, with a 40X coverage. Finally, using machine learning algorithms, we identified unique DMR panels for the detection of various GI cancers. Results: Methylation profiling data from various GI tissues led to the identification of 67,832 DMRs with an adjusted p&amp;lt;0.001 and a delta beta value of 0.2, in all the comparisons across all GI cancers. Subsequent investigation of these tissue-specific DMRs in 300 cf-DNA specimens using our custom SeqCap panel led to the development of three distinct categories of DMR panels: 1) Cancer-specific biomarker panels with an AUC values of 0.98 (CRC), 0.94 (ESCC), 0.90 (EAC), 0.90 (GC), 0.98 (HCC), and 0.85 (PDAC); 2) A pan-GI biomarker panel that detected all GI cancers with an AUC of 0.90; and 3) A multi-cancer prediction panel, EpiPanGI Dx, with a prediction accuracy around 0.85 for most GI cancers. All three groups of DMR panels when trained and tested in the cf-DNA cohorts achieved excellent diagnostic accuracy with AUC values ranging from 0.74-0.98, even for each of the early-stage GI cancers. Conclusions: Utilizing a novel biomarker discovery approach, we provide first evidence for cell-free DNA methylation biomarkers that offer a robust diagnostic accuracy for the identification of specific cancer types, and demonstrate their potential clinical application as a Pan-cancer panel for the early detection of all gastrointestinal cancers. Citation Format: Raju Kandimalla, Jianfeng Xu, Alexander Link, Takatoshi Matsuyama, Kensuke Yamamura, Iqbal Parker, Hiroyuki Uetake, Eva Hernandez-Illan, Juanjo Lozano, Erkut Borazanci, Susan Tsai, Douglas Evans, Stephen J. Meltzer, Hideo Baba, Randall Brand, Daniel Von Hoff, Francesc Balaguer, Wei Li, Ajay Goel. EpiPanGI-Dx: A cell-free DNA methylation fingerprint for the early detection of gastrointestinal cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1084.

P-141 The contribution of white blood cell gene expression in the prediction of gastrointestinal cancer

Gastrointestinal (GI) cancer remains one of the most deadly and common types of cancer worldwide. The early detection of GI cancer contributes to designing more efficient treatment algorithms and therefore reduction in mortality rates. The present study aimed to introduce and evaluate a non-invasive and sensitive technique, able to distinguish between normal and GI cancer samples. The recommended assay is based on the synergy of molecular biology with artificial neural networks.

Circulating ensembles of tumor-associated cells in gastrointestinal cancers.

808 Background: CEA and CA19-9 are non-specific markers for Gastrointestinal (GI) cancers. Molecular analysis of fecal blood is of limited utility in colorectal cancers. A non-invasive pan-GI-cancer blood-based test with high specificity and sensitivity is an unmet medical need. Considering that unprovoked thromboembolism is a significant risk in multiple cancers, we hypothesized that circulating thrombotic emboli in peripheral blood could comprise cancer cells and would serve as a reliable biomarker for detection of GI cancers. Methods: We obtained 15ml of blood from 7481 individuals, including 181 cases of Esophageal cancer, 125 cases of Gastric cancer, 448 cases of colorectal cancer and from 6727 asymptomatic individuals with age related elevated risk who underwent evaluation of serum CA19-9 and AFP. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation and further processes for negative enrichment and harvesting of circulating tumor cell clusters which were characterized by immunostaining. Circulating Ensembles of Tumor Associated Cells (C-ETACs) were defined as clusters of 3 or more cells which were positive for EpCAM and CK, irrespective of CD45 status. Results: C-ETACs were detected in 86.7% of esophageal cancers, 94.4% of gastric cancers and 91.3% of colorectal cancers respectively irrespective of extent (stage / metastatic status) of disease and prior treatments. Overall sensitivity among 754 cancer patients was 90.7%. Among the asymptomatic individuals, C-ETACs were detected in 31 / 366 (8.5%) individuals with elevated CEA and 10 / 152 (6.2%) individuals with elevated CA19-9. C-ETACs were detected in 160 / 5333 (2.9%) of the asymptomatic individuals who had no abnormal findings in any of the said markers. Conclusions: C-ETACs were ubiquitously detected in cancers of Oesophagus, Stomach and Colorectum regardless of stage and treatment status, and pose significant latent risk of thromboembolism and metastasis/recurrence. The relative undetectability of C-ETACs in the asymptomatic cohort indicates causative connection with malignancies and are suitable for screening for these cancers.

Efficiency of Gastrointestinal Cancer Detection by Nematode-NOSE (N-NOSE)

Early detection of gastrointestinal cancer may reduce mortality. Recently, Caenorhabditis elegans has been reported to be capable of differentiating patients with cancers from healthy persons by the smell of urine. This novel technique using C. elegans olfaction has been named as Nematode-NOSE (N-NOSE). We collected 180 urine samples from patients with gastrointestinal cancer and 76 samples from healthy subjects. N-NOSE test was performed using these samples and N-NOSE index was obtained. Quantification of the olfactory behavior of C. elegans was performed as established in past studies. By receiver operating characteristic (ROC) analysis, we examined the diagnostic capability of N-NOSE. ROC analysis revealed that N-NOSE showed an area under the curve value of more than 0.80, even in early-stage cancers. C. elegans olfaction enabled the detection of gastrointestinal cancers from urine with high sensitivity, which can provide the basis for the development of N-NOSE as a gastrointestinal cancer screening test.

The Color Difference between Differentiated Early Gastric Cancer and Suspicious Mucosal Areas on Linked Color Imaging

Background: Image enhanced endoscopy (IEE) contributes to the early detection of gastrointestinal cancer. IEE enhances the color between a lesion and the background mucosa. Linked color imaging (LCI), a novel form of IEE, is a unique system for enhancing color and some studies have demonstrated the efficacy of LCI in the diagnosis of early gastric cancer (EGC) based on the color difference between cancer and the background mucosa. However, the effect may increase the area in which cancer is suspected and lead to an increase in false-positive results. Summary: We conducted a retrospective study of linked color images of differentiated EGC and suspicious mucosal areas to compare the colors between each lesion. Images of 38 EGCs and 23 suspicious areas were analyzed. The mean color values of EGC were as follows; L*(lightness), 61.7; a*(green to red), 41.2; and b*(blue to yellow), 27.1. Those of suspicious mucosal areas were as follows; L*, 56.1; a*, 44.2; and b*, 21.3. EGC had significantly higher L*, b* values and lower a* values in comparison to suspicious mucosal areas. EGC and suspicious mucosal areas had significantly higher a* values in comparison to the background mucosa. Key Messages: EGC had higher b* values in comparison to suspicious mucosal areas, and was not only reddish but also mixed with yellow, with an orange-like color.

Fast stimulated Raman and second harmonic generation imaging for intraoperative gastro-intestinal cancer detection

Conventional haematoxylin, eosin and saffron (HES) histopathology, currently the ‘gold-standard’ for pathological diagnosis of cancer, requires extensive sample preparations that are achieved within time scales that are not compatible with intra-operative situations where quick decisions must be taken. Providing to pathologists a close to real-time technology revealing tissue structures at the cellular level with HES histologic quality would provide an invaluable tool for surgery guidance with evident clinical benefit. Here, we specifically develop a stimulated Raman imaging based framework that demonstrates gastro-intestinal (GI) cancer detection of unprocessed human surgical specimens. The generated stimulated Raman histology (SRH) images combine chemical and collagen information to mimic conventional HES histopathology staining. We report excellent agreements between SRH and HES images acquire on the same patients for healthy, pre-cancerous and cancerous colon and pancreas tissue sections. We also develop a novel fast SRH imaging modality that captures at the pixel level all the information necessary to provide instantaneous SRH images. These developments pave the way for instantaneous label free GI histology in an intra-operative context.

Detection of Premalignant Gastrointestinal Lesions Using Surface-Enhanced Resonance Raman Scattering-Nanoparticle Endoscopy.

Cancers of the gastrointestinal (GI) tract are among the most frequent and most lethal cancers worldwide. An important reason for this high mortality is that early disease is typically asymptomatic, and patients often present with advanced, incurable disease. Even in high-risk patients who routinely undergo endoscopic screening, lesions can be missed due to their small size or subtle appearance. Thus, current imaging approaches lack the sensitivity and specificity to accurately detect incipient GI tract cancers. Here we report our finding that a single dose of a high-sensitivity surface-enhanced resonance Raman scattering nanoparticle (SERRS-NP) enables reliable detection of precancerous GI lesions in animal models that closely mimic disease development in humans. Some of these animal models have not been used previously to evaluate imaging probes for early cancer detection. The studies were performed using a commercial Raman imaging system, a newly developed mouse Raman endoscope, and finally a clinically applicable Raman endoscope for larger animal studies. We show that this SERRS-NP-based approach enables robust detection of small, premalignant lesions in animal models that faithfully recapitulate human esophageal, gastric, and colorectal tumorigenesis. This method holds promise for much earlier detection of GI cancers than currently possible and could lead therefore to marked reduction of morbidity and mortality of these tumor types.

IGFBP-1 As a Serum Protein Biomarker for Early Detection of Gastrointestinal Cancer

Background: Early detection would significantly improve cancer prognosis. We aimed to identify serum protein biomarker for early cancer detection and assess the diagnostic value in various types of cancers. Methods: We performed a three-stage study, and recruited participants of normal controls and seven different types of cancer patients (oesophageal squamous cell carcinoma (ESCC), oesophagogastric junction adenocarcinoma (EJA), stomach cancer, colorectal cancer, lung cancer, nasopharyngeal cancer and breast cancer) from two medical centres. We applied two different antibody arrays to screen candidate serum protein which were increased in 20 ESCC patients compared with 20 matched normal controls. In biomarker assessment stage, the diagnostic value of the selected protein measured by ELISA was evaluated in seven cancer types, and was validated in two independent cohorts of ESCC patients and controls (cohorts 1 and 2). Receiver operating characteristics (ROCs) with the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were used to calculate diagnostic accuracy. Findings: We recruited 1628 participants to biomarker assessment stage: 287 with ESCC, 237 with EJA, 207 with stomach cancer, 138 with colorectal cancer, 126 with lung cancer, 150 with nasopharyngeal cancer, 150 with breast cancer and 333 normal controls, and 472 and 452 participants comprised of ESCC patients and controls to the two independent validation cohorts. Serum IGFBP-1 showed elevated level for ESCC in both antibody arrays. A significant increase in the serum IGFBP-1 level on all cancer types except breast cancer was confirmed by ELISA, compared with normal controls. Serum IGFBP-1 provided a high diagnostic accuracy of gastrointestinal tumours (AUC 0·880-0·938, sensitivity 65·22-77·22%, and specificity 90·39%). Similar results were noted for early-stage gastrointestinal tumours (0·858-0·936, 60·29-83·93%, and 90·39%). In two validation cohorts, serum IGFBP-1 maintained diagnostic performance for early stage ESCC (0·849, 68·04%, and 89·09% in cohort 1, and 0·911, 72·34% and 87·37% in cohort 2). Furthermore, when compared with CEA, Cyfra21-1 and SCCA tested alone or together, serum IGFBP-1 had significantly improved diagnostic accuracy for ESCC and early stage ESCC. Interpretation: Serum IGFBP-1 is a potential biomarker with high diagnostic value for the early detection of gastrointestinal cancer. Funding Statement: This work was supported by funding from the Natural Science Foundation of China (31600632, 81772532 and 81872372), the Population-based prospective cohort study of esophageal cancer and precancerous lesions in high risk areas (2016YFC0901404), the National Cohort of Esophageal Cancer of China (2016YFC0901400), and the Guangdong Esophageal Cancer Institute Science and Technology Program (M201713), the Natural Science Foundation of Guangdong Province (2018A030307079) and the Shantou University Medical College Clinical Research Enhancement Initiative (201428). Declaration of Interests: We declare that we have no conflicts of interest. Ethics Approval Statement: The study was approved by the Institutional Review Boards for Human Research at each hospital, and informed consent was obtained from all participants.

Detection of gastrointestinal cancer: the role of cancer biomarkers

Detection of gastrointestinal cancer: the role of cancer biomarkers

Laparoscopic fluorescence image-guided photothermal therapy enhances cancer diagnosis and treatment.

Endoscopy is the gold standard investigation in the diagnosis of gastrointestinal cancers and the management of early and pre-malignant lesions either by resection or ablation. Recently gold nanoparticles have shown promise in cancer diagnosis and therapeutics (theranostics). The combination of multifunctional gold nanoparticles with near infrared fluorescence endoscopy for accurate mapping of early or pre-malignant lesions can potentially enhance diagnostic efficiency while precisely directing endoscopic near infrared photothermal therapy for established cancers. The integration of endoscopy with near infrared fluorescence imaging and photothermal therapy was aided by the accumulation of our multifunctionalized PEG-GNR-Cy5.5-anti-EGFR-antibody gold nanorods within gastrointestinal tumor xenografts in BALB/c mice. Control mice (with tumors) received either gold nanorods or photothermal therapy, while study mice received both treatment modalities. Local (tumor-centric) and systemic effects were examined for 30 days. Clear endoscopic near infrared fluorescence signals were observed emanating specifically from tumor sites and these corresponded precisely to the tumor margins. Endoscopic fluorescence-guided near infrared photothermal therapy successfully induced tumor ablations in all 20 mice studied, with complete histological clearance and minimal collateral damage. Multi-source analysis from histology, electron microscopy, mass spectrometry, blood, clinical evaluation, psychosocial and weight monitoring demonstrated the inherent safety of this technology. The combination of this innovative nanotechnology with gold standard clinical practice will be of value in enhancing the early optical detection of gastrointestinal cancers and a useful adjunct for its therapy.