DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract.

One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.

Cancer-derived exosomes as novel biomarkers in metastatic gastrointestinal cancer.

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.

Impact of breast-, gastrointestinal-, and lung cancer on prognosis in patients with first-time pulmonary embolism: A Danish nationwide cohort study.

BACKGROUND: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status. METHODS: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method. RESULTS: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer). CONCLUSIONS: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer.

[Gastrointestinal tumour prevention strategies]. / Präventionsstrategien gastrointestinaler Tumoren.

Over the past few decades, substantial advancements have been achieved in the early detection and treatment of gastrointestinal oncological diseases. The survival rates of patients have significantly improved due to the expansion and enhancement of therapeutic and diagnostic options, leading to modifications in (neo-)adjuvant, perioperative, and palliative strategies, as well as the advent of personalized molecular therapy. Noteworthy progress has also been observed in primary, secondary, and tertiary prevention domains.Despite these advancements, gastrointestinal tumours continue to be a global health burden, with approximately 4 million new cases diagnosed annually. These constitute over a quarter of all tumour cases, with nearly one-third of all global tumour-related mortalities attributed to gastrointestinal tumours.Emerging evidence implicates aberrant differentiation of stem or progenitor cells in the pathogenesis of gastrointestinal tumour diseases. A confluence of clinically recognized risk factors, including high-fat diet, bile acid, microbiome alterations, and host factors, can instigate chronic inflammation. This disrupts stem cell homeostasis and precipitates malignant transformation. Consequently, environmental inflammation emerges as a critical risk factor warranting consideration in clinical cancer prevention and surveillance strategies.This review encapsulates the current understanding and recommendations in the prevention of selected gastrointestinal tumours, aiming to facilitate their integration into clinical practice. It underscores the need for continued research to further refine diagnostic and therapeutic strategies and improve patient outcomes.

[Gastrointestinal stromal tumors : Where do we stand?] / Gastrointestinale Stromatumoren : Wo stehen wir?

For more than 20 years gastrointestinal stromal tumors (GIST) have been a paradigm for a targeted treatment with tyrosine kinase inhibitors. A fundamental prerequisite for a neoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of a hereditary or syndromic predisposition must be considered because this results in consequences for the treatment and a different follow-up strategy.

BCAT1, IKZF1 and SEPT9: methylated DNA biomarkers for detection of pan-gastrointestinal adenocarcinomas.

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.

Epidemiological features and prognosis for primary gastrointestinal follicular lymphoma.

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.

Immunohistochemical Expression of Lymphatic Endothelial Markers in Blue Rubber Bleb Nevus Syndrome.

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.

The Role of Screening and Early Detection in Upper Gastrointestinal Cancers.

Upper gastrointestinal cancers are among the leading causes of cancer deaths worldwide with exceptionally poor prognosis, which is largely attributable to frequently delayed diagnosis. Although effective screening is critical for early detection, the highly variable incidence of upper gastrointestinal cancers presents challenges, rendering universal screening programs suboptimal in most populations globally. Optimal strategies in regions of modest incidence, such as the United States, require a targeted approach, focused on high-risk individuals based on demographic, familial, and clinicopathologic risk factors. Assessment of underlying precancerous lesions has key implications for risk stratification and informing clinical decisions to improve patient outcomes.

Upper Gastrointestinal Cancers and the Role of Genetic Testing.

Beyond the few established hereditary cancer syndromes with an upper gastrointestinal cancer component, there is increasing recognition of the contribution of novel pathogenic germline variants (gPVs) to upper gastrointestinal carcinogenesis. The detection of gPVs has potential implications for novel treatment approaches of the index cancer patient as well as long-term implications for surveillance and risk-reducing measures for cancer survivors and far-reaching implications for the patients' family. With widespread availability of multigene panel testing, new associations may be identified with germline-somatic integration being critical to determining true causality of novel gPVs. Comprehensive cancer care should incorporate both somatic and germline testing.

Tumor neuroectodérmico maligno del tracto gastrointestinal: a propósito de un caso / Malignant neuroectodermal tumor of the gastrointestinal tract: case report

El tumor neuroectodérmico maligno del tracto gastrointestinal es una neoplasia rara con pocos casos reportados en la literatura, especialmente en América Latina. Descrito por primera vez en 2003, se trata de una entidad sin tratamiento estandarizado y de pobre pronóstico. Se presenta el caso de una paciente de 22 años de edad que acude a la consulta por dolor abdominal, anemia y masa abdominal palpable. Luego de estudios pertinentes se decide la conducta resectiva y el posterior tratamiento oncológico. (AU)

Malignant gastrointestinal neuroectodermal tumor (GNET), formerly known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare tumor of mesenchymal origin, which presents great microscopic and molecular similarity to clear cell sarcoma found in other parts of the body, such as tendons and aponeurosis. It is characterized by its rapid evolution, high recurrence rate and frequent diagnosis as metastatic disease.1,2 (AU)

Knowledge and awareness of early gastrointestinal cancer screening in Sunan Yugur Autonomous County in Gansu, China.

OBJECTIVE: We aimed to assess the level of knowledge and awareness regarding the need for screening of early gastrointestinal cancer among residents of Sunan Yugur Autonomous County in China. METHODS: In this cross-sectional study, we conducted a survey among permanent residents of Sunan Yugur Autonomous County from January 2020 to January 2023 using a questionnaire to obtain data on knowledge regarding early gastrointestinal cancer screening. RESULTS: The survey included 12,000 residents. Among participants, 62.30% (7476/12,000) were aware of the need for early gastrointestinal cancer screening. Awareness about the need for early gastrointestinal cancer screening differed significantly based on participants' sex, age, level of education, area of residence, and ethnicity. CONCLUSION: The level of awareness regarding the need for early gastrointestinal cancer screening was relatively low in our study population. The government and medical institutions should provide information and promote early gastrointestinal cancer screening in the region to improve the health status and quality of life among the Yugur people.

Essentials of macroscopic evaluation of specimens from gastrointestinal tract.

An astute macroscopic examination, coupled with correlating the gross findings with clinical indication and operative notes along with judicious, yet all pertinent sectioning for pathological examination is crucial for an accurate histopathological diagnosis, eventually leading to optimal patient care. This succinct review highlights the general concepts that lay the foundation of evaluating and grossing specimens from the luminal gastrointestinal (GI) tract. We also discuss the gross evaluation and sectioning of small therapeutic resections, along with a systematic approach and rationale when grossing and submitting histological sections from larger oncological resections from the luminal GI tract. Selected site-specific considerations, for example, grossing treated rectal and oesophageal cancers or taking sections from mucinous tumours of the appendix, among others, are also discussed.

Diagnostic yield of endoscopic and EUS-guided biopsy techniques in subepithelial lesions of the upper GI tract: a systematic review.

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.

Extracellular vesicles associated microRNAs: Their biology and clinical significance as biomarkers in gastrointestinal cancers.

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.