ABSTRACT
Cancer is one of the foremost health problems worldwide and is among the leading causes of death in the United States. Gastrointestinal tract cancers account for almost one third of the cancer-related mortality globally, making it one of the deadliest groups of cancers. Early diagnosis and prompt management are key to preventing cancer-related morbidity and mortality. With advancements in technology and endoscopic techniques, endoscopy has become the core in diagnosis and management of gastrointestinal tract cancers. In this extensive review, the authors discuss the role endoscopy plays in early detection, diagnosis, and management of esophageal, gastric, colorectal, pancreatic, ampullary, biliary tract, and small intestinal cancers.
Subject(s)
Gastroenterology , Gastrointestinal Neoplasms , Humans , United States/epidemiology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Endoscopy/methods , PancreasABSTRACT
Gastrointestinal (GI) cancers, including colorectal, gastric, esophageal, pancreatic, and liver, are associated with high mortality and morbidity rates worldwide. One of the underlying reasons for the poor survival outcomes in patients with these malignancies is late disease detection, typically when the tumor has already advanced and potentially spread to distant organs. Increasing evidence indicates that earlier detection of these cancers is associated with improved survival outcomes and, in some cases, allows curative treatments. Consequently, there is a growing interest in the development of molecular biomarkers that offer promise for screening, diagnosis, treatment selection, response assessment, and predicting the prognosis of these cancers. Extracellular vesicles (EVs) are membranous vesicles released from cells containing a repertoire of biological molecules, including nucleic acids, proteins, lipids, and carbohydrates. MicroRNAs (miRNAs) are the most extensively studied non-coding RNAs, and the deregulation of miRNA levels is a feature of cancer cells. EVs miRNAs can serve as messengers for facilitating interactions between tumor cells and the cellular milieu, including immune cells, endothelial cells, and other tumor cells. Furthermore, recent years have witnessed considerable technological advances that have permitted in-depth sequence profiling of these small non-coding RNAs within EVs for their development as promising cancer biomarkers -particularly non-invasive, liquid biopsy markers in various cancers, including GI cancers. Herein, we summarize and discuss the roles of EV-associated miRNAs as they play a seminal role in GI cancer progression, as well as their promising translational and clinical potential as cancer biomarkers as we usher into the area of precision oncology.
Subject(s)
Extracellular Vesicles , Gastrointestinal Neoplasms , MicroRNAs , Humans , MicroRNAs/genetics , Clinical Relevance , Endothelial Cells/metabolism , Precision Medicine , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/metabolism , Extracellular Vesicles/metabolism , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Biology , Biomarkers/metabolismABSTRACT
Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor and has a significant impact on mortality rates. Nevertheless, the swift advancement of contemporary technology has not seamlessly aligned with the evolution of detection methodologies, resulting in a deficit of innovative and efficient clinical assays for GIC. Given that exosomes are preferentially released by a myriad of cellular entities, predominantly originating from neoplastic cells, this confers exosomes with a composition enriched in cancer-specific constituents. Furthermore, exosomes exhibit ubiquitous presence across diverse biological fluids, endowing them with the inherent advantages of non-invasiveness, real-time monitoring, and tumor specificity. The unparalleled advantages inherent in exosomes render them as an ideal liquid biopsy biomarker for early diagnosis, prognosticating the potential development of GIC metastasis.In this review, we summarized the latest research progress and possible potential targets on cancer-derived exosomes (CDEs) in GIC with an emphasis on the mechanisms of exosome promoting cancer metastasis, highlighting the potential roles of CDEs as the biomarker and treatment in metastatic GIC.
Subject(s)
Exosomes , Gastrointestinal Neoplasms , Humans , Exosomes/pathology , Biomarkers, Tumor , Biomarkers , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Liquid Biopsy/methodsABSTRACT
Primary gastrointestinal follicular lymphoma (PGI-FL) is a rare extra-nodal lymphoma. Its epidemiology and prognosis remain unclear. We performed a retrospective analysis of eligible patients with 1648 PGI-FL and 34 892 nodal FL (N-FL) in the Surveillance, Epidemiology and End Results (SEER) database. The age-adjusted average annual incidence of PGI-FL was 0.111/100000. The median overall survival (OS) for PGI-FL and N-FL patients was 207 and 165 months respectively. The 5-year diffuse large B-cell lymphoma (DLBCL) transformation rates were 2.1% and 2.6% respectively. Age, sex, grade, Ann Arbor stage, primary site and radiation were independent prognostic factors (p < 0.05). Nomograms were constructed to predict 1-, 5- and 10-year OS and disease-specific survival (DSS). The receiver operating characteristic curves and calibration plots showed the established nomograms had robust and accurate performance. Patients were classified into three risk groups according to nomogram score. In conclusion, the incidence of PGI-FL has increased over the past 40 years, and PGI-FL has a better prognosis and a lower DLBCL transformation rate than N-FL. The nomograms were developed and validated as an individualized tool to predict survival. Patients were divided into three risk groups to assist clinicians in identifying high-risk patients and choosing the optimal individualized treatments.
Subject(s)
Gastrointestinal Neoplasms , Lymphoma, Follicular , SEER Program , Humans , Lymphoma, Follicular/mortality , Lymphoma, Follicular/epidemiology , Lymphoma, Follicular/therapy , Lymphoma, Follicular/diagnosis , Female , Male , Middle Aged , Aged , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Adult , Retrospective Studies , Prognosis , Aged, 80 and over , Nomograms , Incidence , Lymphoma, Large B-Cell, Diffuse/epidemiology , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Adolescent , Young AdultABSTRACT
BACKGROUND: There is accumulating evidence supporting the clinical use of circulating tumor DNA (ctDNA) in solid tumors, especially in different types of gastrointestinal cancer. As such, appraisal of the current and potential clinical utility of ctDNA is needed to guide clinicians in decision-making to facilitate its general applicability. CONTENT: In this review, we firstly discuss considerations surrounding specimen collection, processing, storage, and analysis, which affect reporting and interpretation of results. Secondly, we evaluate a selection of studies on colorectal, esophago-gastric, and pancreatic cancer to determine the level of evidence for the use of ctDNA in disease screening, detection of molecular residual disease (MRD) and disease recurrence during surveillance, assessment of therapy response, and guiding targeted therapy. Lastly, we highlight current limitations in the clinical utility of ctDNA and future directions. SUMMARY: Current evidence of ctDNA in gastrointestinal cancer is promising but varies depending on its specific clinical role and cancer type. Larger prospective trials are needed to validate different aspects of ctDNA clinical utility, and standardization of collection protocols, analytical assays, and reporting guidelines should be considered to facilitate its wider applicability.
Subject(s)
Circulating Tumor DNA , Gastrointestinal Neoplasms , Pancreatic Neoplasms , Humans , Circulating Tumor DNA/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/genetics , Prospective StudiesABSTRACT
BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.
Subject(s)
Gastrointestinal Neoplasms , Humans , Spain/epidemiology , Middle Aged , Male , Female , Aged , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Adult , Age of Onset , Life Style , Adenocarcinoma/epidemiology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Tumor Microenvironment , Quality of Life , Incidence , Biomarkers, Tumor , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathologyABSTRACT
BACKGROUND AND AIMS: Obtaining adequate tissue samples in subepithelial lesions (SELs) remains challenging. Several biopsy techniques are available, but a systematic review including all available techniques to obtain a histologic diagnosis of SEL is lacking. The aim of this study was to evaluate the diagnostic yield and adverse event rates of endoscopic biopsies, EUS-guided FNA (EUS-FNA), EUS-guided fine-needle biopsy (FNB) (EUS-FNB), and mucosal incision-assisted biopsy (MIAB) for SELs in the upper GI tract. METHODS: A search strategy in multiple databases was performed. The primary outcome was diagnostic yield, defined as the percentage of procedures in which histology was obtained and resulted in a definitive histopathologic diagnosis. Secondary outcome measures included reported procedure-related adverse events, which were graded according to the AGREE (Adverse Events in Gastrointestinal Endoscopy) classification. RESULTS: A total of 94 original articles were included. Studies were classified per endoscopic technique to obtain histopathology. This resulted in 8 included studies for endoscopic biopsy methods, 55 studies for EUS-FNA, 33 studies for EUS-FNB, and 26 studies for MIAB. Pooled rates for diagnostic yield were 40.6% (95% confidence interval [CI], 30.8-51.2) for endoscopic biopsy, 74.6% (95% CI, 69.9-78.7) for EUS-FNA, 84.2% (95% CI, 80.7-87.2) for EUS-FNB, and 88.2% (95% CI, 84.7-91.1) for MIAB. Reported procedure-related adverse events graded AGREE II or higher were 2.8% to 3.9% for endoscopic biopsies, 1.0% to 4.5% for EUS-FNA, .9% to 7.7% for EUS-FNB, and 1.9% to 7.9% for MIAB. CONCLUSIONS: Based on the available evidence, MIAB and EUS-FNB seem to be most effective in terms of achieving a high diagnostic yield, with similar rates of adverse events.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration/adverse effects , Endosonography/methods , Endoscopy, Gastrointestinal/methods , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/diagnosis , Stomach Neoplasms/pathology , Stomach Neoplasms/diagnosis , Upper Gastrointestinal Tract/pathology , Image-Guided Biopsy/methods , Image-Guided Biopsy/adverse effects , Esophageal Neoplasms/pathology , Esophageal Neoplasms/diagnosisABSTRACT
INTRODUCTION: Well-calibrated models for personalized prognostication of patients with gastrointestinal neuroendocrine neoplasms (GINENs) are limited. This study aimed to develop and validate a machine-learning model to predict the survival of patients with GINENs. METHODS: Oblique random survival forest (ORSF) model, Cox proportional hazard risk model, Cox model with least absolute shrinkage and selection operator penalization, CoxBoost, Survival Gradient Boosting Machine, Extreme Gradient Boosting survival regression, DeepHit, DeepSurv, DNNSurv, logistic-hazard model, and PC-hazard model were compared. We further tuned hyperparameters and selected variables for the best-performing ORSF. Then, the final ORSF model was validated. RESULTS: A total of 43,444 patients with GINENs were included. The median (interquartile range) survival time was 53 (19-102) months. The ORSF model performed best, in which age, histology, M stage, tumor size, primary tumor site, sex, tumor number, surgery, lymph nodes removed, N stage, race, and grade were ranked as important variables. However, chemotherapy and radiotherapy were not necessary for the ORSF model. The ORSF model had an overall C index of 0.86 (95% confidence interval, 0.85-0.87). The area under the receiver operation curves at 1, 3, 5, and 10 years were 0.91, 0.89, 0.87, and 0.80, respectively. The decision curve analysis showed superior clinical usefulness of the ORSF model than the American Joint Committee on Cancer Stage. A nomogram and an online tool were given. CONCLUSION: The machine learning ORSF model could precisely predict the survival of patients with GINENs, with the ability to identify patients at high risk for death and probably guide clinical practice.
Subject(s)
Gastrointestinal Neoplasms , Machine Learning , Neuroendocrine Tumors , Humans , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/therapy , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/pathology , Male , Female , Middle Aged , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/therapy , Aged , Prognosis , Adult , Proportional Hazards Models , NomogramsABSTRACT
BACKGROUND: Despite numerous reports on the alterations of microRNA-1246 (miR-1246) expression level in digestive system cancers, its role in gastrointestinal cancers (GICs) remains unclear. This meta-analysis aimed to assess the diagnostic potential of circulating miR-1246 in GICs. METHODS: Meta-disc version 1.4 and Comprehensive Meta-Analysis (CMA) version 3.7 software were used to calculate pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), area under the curve (AUC), Q*index and summary receiver-operating characteristic (SROC). Subgroup analyses were conducted for cancer type, sample type and geographical region. Publication bias was assessed using Begg's and Egger's tests. RESULTS: A total of 14 articles involving 18 studies and 1526 participants (972 cases and 554 controls) were included. The diagnostic accuracy of miRNA-1246 in GICs was as follows: pooled sensitivity: 0.81 (95% CI: 0.79 - 0.83), specificity: 0.74 (95% CI: 0.71 - 0.77), PLR: 3.315 (95% CI: 2.33 - 4.72), NLR: 0.221 (95% CI: 0.153 - 0.319), DOR: 16.87 (95% CI: 9.45 - 30.09), AUC: 0.891, and Q*-index: 0.807. No publication bias was found based on Begg's (p = 0.172) and Egger's (p = 0.113) tests. CONCLUSION: Circulating miR-1246 shows promise as a non-invasive biomarker for early detection of GICs.
Subject(s)
Biomarkers, Tumor , Gastrointestinal Neoplasms , MicroRNAs , Humans , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/blood , Gastrointestinal Neoplasms/genetics , MicroRNAs/blood , MicroRNAs/genetics , ROC Curve , Sensitivity and Specificity , Circulating MicroRNA/blood , Circulating MicroRNA/geneticsABSTRACT
INTRODUCTION: Methylated circulating tumour DNA (ctDNA) blood tests for BCAT1/IKZF1 (COLVERA) and SEPT9 (Epi proColon) are used to detect colorectal cancer (CRC). However, there are no ctDNA assays approved for other gastrointestinal adenocarcinomas. We aimed to characterize BCAT1, IKZF1 and SEPT9 methylation in different gastrointestinal adenocarcinoma and non-gastrointestinal tumours to determine if these validated CRC biomarkers might be useful for pan-gastrointestinal adenocarcinoma detection. METHODS: Tissue DNA methylation data from colorectal (COAD, READ), gastroesophageal (ESCA, STAD), pancreatic (PAAD) and cholangiocarcinoma (CHOL) adenocarcinoma cohorts within The Cancer Genome Atlas were used for differential methylation analyses. Clinicodemographic predictors of BCAT1, IKZF1 and SEPT9 methylation, and the selectivity of hypermethylated BCAT1, IKZF1 and SEPT9 for colorectal adenocarcinomas in comparison to other cancers were each explored with beta regression. RESULTS: Hypermethylated BCAT1, IKZF1 and SEPT9 were each differentially methylated in colorectal and gastroesophageal adenocarcinomas. IKZF1 was differentially methylated in pancreatic adenocarcinoma. Hypermethylated DNA biomarkers BCAT1, IKZF1 and SEPT9 were largely stable across different stages of disease and were highly selective for gastrointestinal adenocarcinomas relative to other cancer types. DISCUSSION: Existing CRC methylated ctDNA blood tests for BCAT1/IKZF1 and SEPT9 might be usefully repurposed for use in other gastrointestinal adenocarcinomas and warrant further prospective ctDNA studies.
Subject(s)
Adenocarcinoma , Biomarkers, Tumor , DNA Methylation , Gastrointestinal Neoplasms , Ikaros Transcription Factor , Septins , Humans , Septins/genetics , Septins/blood , Ikaros Transcription Factor/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Adenocarcinoma/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/blood , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/blood , Male , Circulating Tumor DNA/genetics , Circulating Tumor DNA/blood , Female , Colorectal Neoplasms/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/blood , Cholangiocarcinoma/genetics , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/blood , Middle Aged , Pancreatic Neoplasms/genetics , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/bloodABSTRACT
OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.
Subject(s)
Deep Learning , Diagnosis, Computer-Assisted , Endosonography , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , ROC Curve , Humans , Diagnosis, Differential , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Neoplasms/diagnostic imaging , Gastrointestinal Neoplasms/diagnosis , Female , Middle Aged , Male , Aged , Adult , Risk Assessment , Sensitivity and Specificity , Aged, 80 and overABSTRACT
PURPOSEOF REVIEW: This review examines the challenges of treating gastrointestinal cancer in the aging population, focusing on the importance of frailty assessment. Emphasized are the rise in gastrointestinal cancer incidence in older adults, advances in frailty assessments for patients with gastrointestinal cancer, the development of novel frailty markers, and a summary of recent trials. RECENT FINDINGS: Increasing evidence suggests that the use of a Comprehensive Geriatric Assessment (CGA) to identify frail older adults and individualize cancer care leads to lower toxicity and improved quality of life outcomes. However, the adoption of a full CGA prior to chemotherapy initiation in older cancer patients remains low. Recently, new frailty screening tools have emerged, including assessments designed to specifically predict chemotherapy-related adverse events. Additionally, frailty biomarkers have been developed, such as blood tests like IL-6 and performance tracking through physical activity monitors. The relevance of nutrition and muscle mass is discussed. Highlights from recent trials suggest the feasibility of successfully identifying patients most at risk of serious adverse events. There have been promising developments in identifying novel frailty markers and methods to screen for frailty in the older adult population. Further prospective trials that focus on and address the needs of the geriatric population for early identification of frailty in cancer care, facilitating a more tailored treatment approach. Practicing oncologists should select a frailty assessment to implement into their routine practice and adjust treatment accordingly.
Subject(s)
Frailty , Gastrointestinal Neoplasms , Humans , Aged , Frailty/diagnosis , Quality of Life , Frail Elderly , Gastrointestinal Neoplasms/diagnosis , Risk Assessment , Geriatric Assessment/methodsABSTRACT
To assess the diagnostic efficacy of SEPT9 along with PAX5 gene methylation detection in gastrointestinal cancer and precancerous lesions, the peripheral blood of 62 patients with gastric cancer (GC) and 60 patients with no evidence of disease (as the control group) were retrospectively collected. The methylation rates of PAX5 and SEPT9 gene promoters in blood samples of GC group were detected by PCR. At the same time, the differences in methylation rates of genes in the two groups were compared, and the predictive value of plasma methylation PAX5 and SEPT9 in GC was evaluated by receiver operating characteristic (ROC) curve. We found that there were 41 cases of methylated PAX5 gene promoter region and 39 cases of methylated SEPT9 gene promoter region in GC group. The control group contained 14 cases of PAX5 gene promoter methylation and 12 cases of RNF¹80 gene promoter methylation. The occurrence of PAX5 promoter methylation was correlated with age of GC patients. There were statistically significant differences in mSEPT9 gene in patients with different TNM stages. Kaplan-Meier survival curve analysis revealed that the three-year overall survival rate of GC patients with PAX5 methylation was lower than that of GC patients without PAX5 methylation. No significant difference was discovered in 3-year overall survival rate between GC patients with SEPT9 methylation and those without SEPT9 methylation. Combined detection could not improve the diagnostic value of GC, but could promote diagnosis sensitivity. In summary, the risk of PAX5 and SEPT9 gene methylation in GC patients presents higher when compared with healthy people. PAX5 gene methylation is closely related to age, while SEPT9 is closely related to tumor TNM stage, and PAX5 gene methylation can decrease the survival rate of GC patients. Detection of PAX5 gene methylation level can assist in evaluating the prognosis of GC patients.
Subject(s)
DNA Methylation , PAX5 Transcription Factor , Precancerous Conditions , Promoter Regions, Genetic , Septins , Humans , Septins/genetics , DNA Methylation/genetics , PAX5 Transcription Factor/genetics , PAX5 Transcription Factor/metabolism , Female , Male , Middle Aged , Promoter Regions, Genetic/genetics , Aged , Precancerous Conditions/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , ROC Curve , Kaplan-Meier Estimate , Stomach Neoplasms/genetics , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Adult , Biomarkers, Tumor/genetics , Retrospective Studies , Neoplasm StagingABSTRACT
BACKGROUND: Pediatric granular cell tumors (GCT) involving the gastrointestinal tract (GIT) are rare with limited case report/series reported to date. METHODS: Multicenter retrospective study of pediatric GIT GCT. RESULTS: A total of 10 cases were included in the study with a median age of 13.5 years (range: 7-18 years) and were predominantly female patients (60%). In half of the patients no significant medical history was present with the remaining 5 having Crohn disease (10%), eosinophilic esophagitis (EoE) (10%), Crohn disease and EoE (10%), growth hormone deficiency (10%), and aplasia cutis congenita (10%). The GCT median size was 1.3 cm (range: 1-1.6 cm) and were more commonly located in the esophagus (70%) followed by the stomach (20%) and rectum (10%). Most of the cases showed round/polygonal tumor cells with abundant granular cytoplasm, and none of the cases had nuclear atypia, increased mitotic activity, or tumor cell necrosis. None of our cases received specific therapy for GCT other than clinical follow-up, and none of the patients had evidence of local recurrence or metastatic disease. CONCLUSION: We present our multicenter experience with GIT GCT, all cases had a benign course. Interestingly, 4 of the esophageal GCT cases (including 2 patients with EoE) showed an eosinophil-rich esophagitis in the underlying mucosa.
Subject(s)
Gastrointestinal Neoplasms , Granular Cell Tumor , Humans , Granular Cell Tumor/pathology , Granular Cell Tumor/diagnosis , Adolescent , Female , Child , Male , Retrospective Studies , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/diagnosisABSTRACT
BACKGROUND: The cutoff value for stereomicroscopic on-site evaluation (SOSE) in endoscopic ultrasound-guided tissue acquisition (EUS-TA) has high diagnostic sensitivity when a Franseen needle is employed for upper gastrointestinal subepithelial lesions (SELs) (stereomicroscopically visible white core [SVWC] ≥ 4 mm). AIM: We aimed to determine whether high diagnostic sensitivity could be obtained when EUS-TA was performed using a Fork-tip needle. METHODS: Twenty-one patients were prospectively registered. Patients underwent EUS-TA using a Fork-tip needle for upper gastrointestinal SELs at Kitasato University Hospital between January and November 2022. Punctures were made twice using the needle, and SOSE was conducted for each specimen. Blood and physical examination were performed to assess adverse events. Pathological diagnosis was made using hematoxylin and eosin-stained sections and immunohistochemical staining. Statistical comparisons were completed using Fisher's exact tests. RESULTS: The diagnostic rate of EUS-TA was 100% (21/21 cases). The final diagnosis was gastrointestinal stromal tumor in 17 (81.0%) and leiomyoma in 4 (19.0%) patients. SOSE was conducted on all 42 punctures, and the tissue sampling rate was 100% (42/42 punctures). Specimens with SVWC ≥ 4 mm were collected in 97.6% punctures (41/42 punctures) and the diagnostic sensitivity for these specimens was 100% (41/41 punctures), which is significantly higher (p < 0.0238) compared to the absence of cutoff value (diagnostic sensitivity of 0%). No EUS-TA-related adverse events occurred. CONCLUSIONS: EUS-TA combined with SOSE for upper gastrointestinal SEL using a fork-tip needle had a high diagnostic rate, and the cutoff value of SVWC ≥ 4 mm had high diagnostic sensitivity.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration , Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Needles , Humans , Female , Male , Middle Aged , Aged , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/diagnosis , Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Adult , Prospective Studies , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/diagnostic imaging , Leiomyoma/pathology , Leiomyoma/diagnostic imaging , Aged, 80 and overABSTRACT
INTRODUCTION: Blue rubber bleb nevus syndrome (BRBNS) is an uncommon vascular anomaly characterized by multifocal cutaneous, visceral, and other soft tissue or solid organ venous malformations. We observed that BRBNS lesions express immunohistochemical markers of lymphatic differentiation. METHODS: BRBNS histopathologic specimens assessed at our institution during the past 27 years were reviewed. Slides from 19 BRBNS lesions were selected from 14 patients (9 cutaneous, 9 gastrointestinal, and 1 hepatic). We recorded the involved anatomical compartments and presence/absence of thrombi or vascular smooth muscle. Immunohistochemical endothelial expression of PROX1 (nuclear) and D2-40 (membranous/cytoplasmic) was evaluated semi-quantitatively. RESULTS: Endothelial PROX1 immunopositivity was noted in all specimens; the majority (89.5%) demonstrated staining in more than 10% of cells. D2-40 immunopositivity was present in one-third (33%) of cutaneous lesions and only 1 gastrointestinal lesion. CONCLUSION: Endothelial cells in BRBNS almost always express 1 or more immunohistochemical markers of lymphatic differentiation.
Subject(s)
Biomarkers, Tumor , Gastrointestinal Neoplasms , Immunohistochemistry , Nevus, Blue , Skin Neoplasms , Humans , Nevus, Blue/metabolism , Nevus, Blue/pathology , Nevus, Blue/diagnosis , Skin Neoplasms/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/diagnosis , Male , Child , Female , Child, Preschool , Adolescent , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/diagnosis , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/analysis , Infant , Tumor Suppressor Proteins/metabolism , Tumor Suppressor Proteins/analysis , Homeodomain Proteins/metabolism , Endothelium, Lymphatic/metabolism , Endothelium, Lymphatic/pathology , Antibodies, Monoclonal, Murine-Derived/metabolismABSTRACT
Liquid biopsy is a test that allows for the diagnosis and analysis of cancer by sampling cancer cells or byproducts present in biological fluids such as blood or urine. It has the potential to create a new paradigm in oncologic care, being a less invasive approach than conventional tissue biopsy. Liquid biopsy has multifaceted applications for longitudinal disease monitoring in terms of surveillance, treatment response, and identification of emerging resistance mechanisms. Multiple assays currently exist or are in development for detecting circulating tumor cells, DNA, RNA, exosomes, proteins, fragmentomic markers, and metabolomes. Here, we review the applications of liquid biopsy in gastrointestinal cancers, emphasizing its use in both perioperative and advanced settings. We also examine its role in screening, diagnostics, and other cancer-related scenarios.
Subject(s)
Gastrointestinal Neoplasms , Neoplastic Cells, Circulating , Humans , Gastrointestinal Neoplasms/diagnosis , Liquid Biopsy , Biopsy , Medical OncologyABSTRACT
The long-term impact of the coronavirus disease 2019 (COVID-19) pandemic on the disruption of gastrointestinal cancer diagnoses remains unclear. This study investigated the actual impact on esophagogastric cancer (EGC) and colorectal cancer (CRC) diagnoses up to the third year of the pandemic in Akita Prefecture, Japan, using population-based registry data. We collected data on the annual number of EGC and CRC diagnoses using a database from the collaborative Akita Prefecture hospital-based registration. The net number of cancers diagnosed in the first three years of the pandemic (2020-2022) were compared with those diagnosed in the three years before the pandemic (2017-2019). Changes in the proportion of cancer stage and initial treatment for diagnosed EGC and CRC after the pandemic were then compared. The total number of EGCs was 9.3% lower in the first three years of the pandemic than in the three years before, probably due to its long-term declining trend. The total number of CRCs in the first three years of the pandemic exceeded that in the three years before, suggesting successful recovery of the diagnostic procedure. The proportion of cancer stages and initial treatment for EGCs and CRCs remained largely unchanged after the onset of the pandemic. Based on the population-based registry data from the first three years of the pandemic, the disruption of gastrointestinal cancer diagnoses caused by the pandemic is settling down without any substantial disease progression, even in Akita Prefecture, the area with the highest incidence of cancer in all of Japan.
Subject(s)
COVID-19 , Gastrointestinal Neoplasms , Humans , COVID-19/epidemiology , Japan/epidemiology , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/diagnosis , Registries , Pandemics , SARS-CoV-2 , Male , Female , Neoplasm Staging , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/diagnosisABSTRACT
The Ki-67 proliferative index plays a pivotal role in the subclassification of neuroendocrine neoplasm (NEN) according to the WHO Classification of Digestive System Tumors (5th edition), which designates neuroendocrine tumor (NET) grades 1, 2, and 3 for Ki-67 proliferative index of <3 %, 3-20 %, and >20 %, respectively. Proliferative index calculation must be performed in the hotspot, traditionally selected by visual scanning at low-power magnification. Recently, gradient map visualization has emerged as a tool for various purposes, including hotspot selection. This study includes 97 cases of gastrointestinal neuroendocrine neoplasms, with hotspots selected by bare eye and gradient map visualization (GM). Each hotspot was analyzed using three methods: eye estimation (EE), digital image analysis (DIA), and manual counting. Of the NENs studied, 91 % were NETs (26 % for G1, 55 % for G2, and 10 % for G3). Only 9 cases were neuroendocrine carcinoma (NEC). Between two hotspot selection methods, GM resulted in a higher grade in 14.77 % of cases, primarily upgrading from NET G1 to G2. Among the counting methods, DIA demonstrated substantial agreement with manual counting, both for pathologist and resident. Grading by other methods tended to result in a higher grade than MC (26.99 % with EE and 8.52 % with DIA). Given its clinical and statistical significance, this study advocates for the application of GM in hotspot selection to identify higher-grade tumors. Furthermore, DIA provides accurate grading, offering time efficiency over MC.
Subject(s)
Image Processing, Computer-Assisted , Ki-67 Antigen , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Ki-67 Antigen/metabolism , Ki-67 Antigen/analysis , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/diagnosis , Image Processing, Computer-Assisted/methods , Neoplasm Grading/methods , Intestinal Neoplasms/pathology , Intestinal Neoplasms/diagnosis , Female , Male , Middle Aged , Aged , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/diagnosis , Adult , Mitotic Index/methods , Carcinoma, Neuroendocrine/pathology , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/metabolism , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/diagnosisABSTRACT
Esophagogastroduodenoscopy (EGD) screening is being implemented in countries with a high incidence of upper gastrointestinal (UGI) cancer. High-quality EGD screening ensures the yield of early diagnosis and prevents suffering from advanced UGI cancer and minimal operational-related discomfort. However, performance varied dramatically among endoscopists, and quality control for EGD screening remains suboptimal. Guidelines have recommended potential measures for endoscopy quality improvement and research has been conducted for evidence. Moreover, artificial intelligence offers a promising solution for computer-aided diagnosis and quality control during EGD examinations. In this review, we summarized the key points for quality assurance in EGD screening based on current guidelines and evidence. We also outline the latest evidence, limitations, and future prospects of the emerging role of artificial intelligence in EGD quality control, aiming to provide a foundation for improving the quality of EGD screening.