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1.
J Transl Med ; 22(1): 429, 2024 May 06.
Article En | MEDLINE | ID: mdl-38711123

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.


Gastritis, Atrophic , Gastrointestinal Neoplasms , Humans , Gastritis, Atrophic/complications , Gastritis, Atrophic/epidemiology , Risk Factors , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/pathology , Chronic Disease , Incidence , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/pathology , Stomach Neoplasms/epidemiology , Stomach Neoplasms/pathology , Male , Odds Ratio , Female , Publication Bias
2.
Acta Oncol ; 63: 288-293, 2024 May 07.
Article En | MEDLINE | ID: mdl-38712513

INTRODUCTION: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.


Antineoplastic Agents , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Quality of Life , Humans , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/therapy , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/surgery , Imatinib Mesylate/therapeutic use , Male , Female , Middle Aged , Aged , Prospective Studies , Antineoplastic Agents/therapeutic use , Adult , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/therapy , Withholding Treatment , Remission Induction , Progression-Free Survival , Neoplasm Metastasis , Aged, 80 and over , Protein Kinase Inhibitors/therapeutic use
3.
PLoS One ; 19(5): e0302880, 2024.
Article En | MEDLINE | ID: mdl-38718092

Gastrointestinal (GI) cancer is leading general tumour in the Gastrointestinal tract, which is fourth significant reason of tumour death in men and women. The common cure for GI cancer is radiation treatment, which contains directing a high-energy X-ray beam onto the tumor while avoiding healthy organs. To provide high dosages of X-rays, a system needs for accurately segmenting the GI tract organs. The study presents a UMobileNetV2 model for semantic segmentation of small and large intestine and stomach in MRI images of the GI tract. The model uses MobileNetV2 as an encoder in the contraction path and UNet layers as a decoder in the expansion path. The UW-Madison database, which contains MRI scans from 85 patients and 38,496 images, is used for evaluation. This automated technology has the capability to enhance the pace of cancer therapy by aiding the radio oncologist in the process of segmenting the organs of the GI tract. The UMobileNetV2 model is compared to three transfer learning models: Xception, ResNet 101, and NASNet mobile, which are used as encoders in UNet architecture. The model is analyzed using three distinct optimizers, i.e., Adam, RMS, and SGD. The UMobileNetV2 model with the combination of Adam optimizer outperforms all other transfer learning models. It obtains a dice coefficient of 0.8984, an IoU of 0.8697, and a validation loss of 0.1310, proving its ability to reliably segment the stomach and intestines in MRI images of gastrointestinal cancer patients.


Gastrointestinal Neoplasms , Gastrointestinal Tract , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging/methods , Gastrointestinal Neoplasms/diagnostic imaging , Gastrointestinal Neoplasms/pathology , Gastrointestinal Tract/diagnostic imaging , Semantics , Image Processing, Computer-Assisted/methods , Female , Male , Stomach/diagnostic imaging , Stomach/pathology
4.
Methods Cell Biol ; 186: 25-49, 2024.
Article En | MEDLINE | ID: mdl-38705603

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.


Flow Cytometry , Gastrointestinal Neoplasms , Genomic Instability , Humans , Flow Cytometry/methods , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Genomic Instability/genetics , Precancerous Conditions/genetics , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Tissue Fixation/methods , Paraffin Embedding/methods , DNA/genetics , DNA/analysis , Gastrointestinal Tract/pathology , Gastrointestinal Tract/metabolism , Barrett Esophagus/genetics , Barrett Esophagus/pathology , Barrett Esophagus/diagnosis
5.
Clin Adv Hematol Oncol ; 22(4): 162-173, 2024 May.
Article En | MEDLINE | ID: mdl-38739719

Locally advanced gastrointestinal (GI) malignancies have conventionally been treated in a multimodal fashion that combines (neo)adjuvant chemotherapy with or without radiation and definitive surgical resection. Clinical data have demonstrated the reduced responsiveness of GI malignancies with microsatellite instability (MSI) to both adjuvant and neoadjuvant systemic chemotherapy when compared with microsatellite stable (MSS) disease. The elevated tumor mutational burden associated with MSI tumors of all types sensitizes these tumors to the effects of immune checkpoint blockade in the metastatic setting, which led to tumor-agnostic approval of immune checkpoint inhibitors in this context. The recent demonstration of greater sensitivity and high pathologic complete response rates to neoadjuvant immunotherapy in locally advanced GI malignancies may ultimately establish a novel treatment paradigm and herald potential nonoperative management of this distinct subgroup of GI malignancies. This article provides an overview of immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies. It also covers the clinical significance of MSI status across the GI cancer spectrum, the available data demonstrating differential responses of MSI and MSS disease to conventional chemotherapy, and the biological rationale for novel strategies utilizing immunotherapy in the neoadjuvant, adjuvant, and nonoperative settings.


Gastrointestinal Neoplasms , Immune Checkpoint Inhibitors , Microsatellite Instability , Humans , Immune Checkpoint Inhibitors/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Neoadjuvant Therapy , Immunotherapy/methods
6.
Appl Immunohistochem Mol Morphol ; 32(5): 229-232, 2024.
Article En | MEDLINE | ID: mdl-38584487

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms with variable behavior characterized by differentiation toward the interstitial cells of Cajal occurring anywhere in the gastrointestinal stromal tract. Frequently, GISTs have fibrous stroma within tumor cell proliferation areas, which is unlike other types of malignant tumors. If this desmoplasia is active, there is a possibility that some sort of transmitter exists between GIST cells and cells related to fibrosis in the tumor cell proliferation areas. Transforming growth factor (TGF)-ß isoforms, particularly TGF-ß1, are critical for fibrosis pathogenesis. TGF-ß1 regulation of myofibroblasts and fibroblasts during fibrosis is well described. The induced fibroblast activation resulting in myofibroblast differentiation has been reported as an important source of collagen, glycoproteins, proteoglycans, and matrix metallopeptidases in wound healing and fibrosis. However, there are a few reports on the relationship between TGF-ß1 and GISTs. This study aims to clarify TGF-ß1 expression in 30 gastric GISTs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we also enrolled 30 samples of gastric tubular adenocarcinoma (GTAC). We confirmed TGF-ß1 expression (H-score ≥50 points) in 57% of GIST and 13% of GTAC samples, a significant difference between the 2 tumor types ( P =0.001). We examined the TGF-ß1 mRNA expression of 3 representative GIST samples, each having their respective immunostained areas detected by RT-PCR. Finding TGF-ß1 expression may indicate that this cytokine plays a part in the formation of desmoplasia within GIST cell proliferative areas.


Gastrointestinal Stromal Tumors , Transforming Growth Factor beta1 , Gastrointestinal Stromal Tumors/metabolism , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/genetics , Humans , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/genetics , Female , Male , Middle Aged , Aged , Immunohistochemistry , Gene Expression Regulation, Neoplastic , Adult , Fibrosis , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Aged, 80 and over
7.
Eur J Pharmacol ; 973: 176563, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38593929

Abnormalities in epigenetic modifications can cause malignant transformations in cells, leading to cancers of the gastrointestinal (GI) tract, which accounts for 20% of all cancers worldwide. Among the epigenetic alterations, DNA hypomethylation is associated with genomic instability. In addition, CpG methylation and promoter hypermethylation have been recognized as biomarkers for different malignancies. In GI cancers, epigenetic alterations affect genes responsible for cell cycle control, DNA repair, apoptosis, and tumorigenic-specific signaling pathways. Understanding the pattern of alterations in DNA methylation in GI cancers could help scientists discover new molecular-based pharmaceutical treatments. This study highlights alterations in DNA methylation in GI cancers. Understanding epigenetic differences among GI cancers may improve targeted therapies and lead to the discovery of new diagnostic biomarkers.


DNA Methylation , Epigenesis, Genetic , Gastrointestinal Neoplasms , DNA Methylation/genetics , Humans , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Animals , Gene Expression Regulation, Neoplastic , Biomarkers, Tumor/genetics
8.
Cancer Med ; 13(8): e7131, 2024 Apr.
Article En | MEDLINE | ID: mdl-38629255

BACKGROUND: More than half of neuroendocrine tumor (NET) patients will experience liver metastasis, and interventional therapy represented by transarterial embolization (TAE) is the main local treatment method. Surufatinib is recommended as a standard systemic treatment for advanced NETs. The efficacy and safety of surufatinib combined with TAE in the treatment of liver metastasis are undetermined. This study was conducted to compare the clinical outcome of surufatinib combined with TAE versus surufatinib monotherapy in liver metastatic NETs. METHODS: This is a prospective, multicenter, open-label, and randomized controlled trial. Patients diagnosed with liver metastatic NETs will be enrolled. Participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group. Patients will be treated with surufatinib plus TAE in the experimental group, while patients in the control group will receive surufatinib monotherapy. The primary endpoint is progression-free survival (PFS) assessed by a blinded independent image review committee (BIIRC). The secondary endpoints are investigator-assessed PFS, liver-specific objective response rate (ORR), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and incidence of adverse events. DISCUSSION: This is the first prospective study to investigate the efficacy of surufatinib combined with TAE. We expect this trial to propose a new and effective treatment strategy for liver metastatic NETs.


Gastrointestinal Neoplasms , Indoles , Liver Neoplasms , Neuroendocrine Tumors , Pyrimidines , Sulfonamides , Humans , Prospective Studies , Neuroendocrine Tumors/drug therapy , Neuroendocrine Tumors/pathology , Gastrointestinal Neoplasms/pathology , Liver Neoplasms/drug therapy , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
9.
Medicine (Baltimore) ; 103(16): e37877, 2024 Apr 19.
Article En | MEDLINE | ID: mdl-38640263

RATIONALE: Inflammatory fibroid polyp (IFP), also known as Vanek tumor, is a rare, benign gastrointestinal lesion characterized by its inflammatory and fibroid histological features. IFP is often discovered incidentally during endoscopic examinations. It is exceedingly rare for an IFP to prolapse into the duodenum and results in incomplete obstruction of the pylorus. PATIENT CONCERNS: A 64-year-old male patient was admitted to the hospital with recurrent episodes of melena over a 6-month period, along with complaints of dizziness and fatigue in the past 10 days. DIAGNOSES: Gastroscopy showed a giant polypoid mass on the posterior wall of the gastric antrum, prolapsing into the duodenum. Abdominal computer tomography (CT) confirmed the tumor protruding into the duodenum. Pathologic examination of the resected specimen confirmed the IFP diagnosis. INTERVENTIONS: The giant tumor was completely and successfully excised using endoscopic submucosal dissection (ESD). After the surgery, the patient underwent acid suppression and fluid replenishment therapy. OUTCOMES: The patient responded well to ESD and was discharged in stable condition. As of the submission of the case report, there has been no recurrence of the tumor after a 5-month follow-up, and the patient is still under follow-up. LESSONS: While IFPs have traditionally been managed surgically, ESD demonstrates promising treatment outcomes, avoiding the need for surgical distal gastrectomy, and emerges as a safe and effective treatment option.


Endoscopic Mucosal Resection , Gastrointestinal Neoplasms , Leiomyoma , Polyps , Stomach Neoplasms , Male , Humans , Middle Aged , Pyloric Antrum/surgery , Pyloric Antrum/pathology , Stomach Neoplasms/complications , Stomach Neoplasms/surgery , Stomach Neoplasms/diagnosis , Polyps/complications , Polyps/surgery , Gastroscopy , Gastrointestinal Neoplasms/pathology , Duodenum/pathology , Leiomyoma/complications , Leiomyoma/surgery , Leiomyoma/pathology
10.
Support Care Cancer ; 32(5): 279, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38594390

PURPOSE: This study aims to (1) explore the prevalence of patient-reported financial difficulties among GIST patients, differentiating between those currently undergoing tyrosine kinase inhibitor (TKI) treatment and those who are not; (2) investigate associations between financial difficulties and sociodemographic and clinical characteristics, work, cancer-related concerns, anxiety and depression and (3) study the impact of financial difficulties on health-related quality of life. METHODS: A cross-sectional study was conducted among Dutch GIST patients diagnosed between 2008 and 2018, who were invited to complete a one-time survey between September 2020 and June 2021. Patients completed nine items of the EORTC item bank regarding financial difficulties, seven work-related questions, the Hospital Anxiety and Depression Scale, Cancer Worry Scale and EORTC QLQ-C30. RESULTS: In total, 328 GIST patients participated (response rate 63.0%), of which 110 (33.8%) were on TKI treatment. Patients currently treated with TKIs reported significantly more financial difficulties compared to patients not on TKIs (17.3% vs 8.7%, p = 0.03). The odds of experiencing financial difficulties was 18.9 (95% CI 1.7-214.7, p = 0.02) times higher in patients who were less able to work due to their GIST diagnosis. Patients who experienced financial difficulties had significantly lower global quality of life and functioning, and more frequently reported psychological symptoms as compared to patients who did not report financial difficulties. CONCLUSION: Even in a country where the costs of TKIs and follow-up care are covered by health insurance, financial difficulties can be present in GIST patients, especially in patients on TKI treatment, and may negatively influence the quality of life.


Gastrointestinal Neoplasms , Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/epidemiology , Cross-Sectional Studies , Quality of Life , Netherlands/epidemiology , Protein Kinase Inhibitors/therapeutic use , Gastrointestinal Neoplasms/pathology
11.
Int J Oncol ; 64(6)2024 06.
Article En | MEDLINE | ID: mdl-38666531

Digestive tract cancer is one of the most common types of cancers globally, with ~4.8 million new cases and 3.4 million cancer­associated deaths in 2018, accounting for 26% of cancer incidence and 35% of cancer­related deaths worldwide. S100 protein family is involved in regulating cancer cell proliferation, angiogenesis, epithelial­mesenchymal transition (EMT), metastasis, metabolism and immune microenvironment homeostasis. The critical role of S100 protein family in digestive tract cancer involves complicated mechanisms, such as cancer stemness remodeling, anaerobic glycolysis regulation, tumor­associated macrophage differentiation and EMT. The present study systematically reviewed published studies on the compositions, function and the underlying molecular mechanisms of the S100 family, as well as guidance for diagnosis, treatment and prognosis of digestive tract cancer. Systematic review of the roles and underlying molecular mechanisms of S100 protein family may provide new insight into exploring potential cancer biomarkers and the optimized therapeutic strategies for digestive tract cancer.


Biomarkers, Tumor , Epithelial-Mesenchymal Transition , S100 Proteins , Humans , Biomarkers, Tumor/metabolism , Cell Proliferation , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Neovascularization, Pathologic/metabolism , Prognosis , S100 Proteins/metabolism , Tumor Microenvironment/immunology
12.
Int Rev Cell Mol Biol ; 385: 41-99, 2024.
Article En | MEDLINE | ID: mdl-38663962

Gastrointestinal carcinomas are a group of cancers associated with the digestive system and its accessory organs. The most prevalent cancers related to the gastrointestinal tract are colorectal, gall bladder, gastric, hepatocellular, and esophageal cancers, respectively. Molecular aberrations in different signaling pathways, such as signal transduction systems or developmental pathways are the chief triggering mechanisms in different cancers Though a massive advancement in diagnostic and therapeutic interventions results in improved survival of patients with gastrointestinal cancer; the lower malignancy stages of these carcinomas are comparatively asymptomatic. Various gastrointestinal-related cancers are detected at advanced stages, leading to deplorable prognoses and increased rates of recurrence. Recent molecular studies have elucidated the imperative roles of several signaling pathways, namely Wnt, Hedgehog, and Notch signaling pathways, play in the progression, therapeutic responsiveness, and metastasis of gastrointestinal-related cancers. This book chapter gives an interesting update on recent findings on the involvement of developmental signaling pathways their mechanistic insight in gastrointestinalcancer. Subsequently, evidences supporting the exploration of gastrointestinal cancer related molecular mechanisms have also been discussed for developing novel therapeutic strategies against these debilitating carcinomas.


Disease Progression , Gastrointestinal Neoplasms , Humans , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/metabolism , Animals , Carcinogenesis/pathology , Carcinogenesis/metabolism , Signal Transduction
13.
Front Immunol ; 15: 1359914, 2024.
Article En | MEDLINE | ID: mdl-38646539

Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy's evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer's immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.


Gastrointestinal Neoplasms , Signal Transduction , Humans , Gastrointestinal Neoplasms/immunology , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/metabolism , Animals , Neoplasm Metastasis , Immune Tolerance , Tumor Escape
14.
Int J Surg ; 110(4): 2151-2161, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38619177

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.


Antineoplastic Agents , Gastrointestinal Stromal Tumors , Hepatectomy , Imatinib Mesylate , Liver Neoplasms , Humans , Gastrointestinal Stromal Tumors/therapy , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/secondary , Imatinib Mesylate/therapeutic use , Imatinib Mesylate/administration & dosage , Male , Female , Middle Aged , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Retrospective Studies , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Adult , Aged , Combined Modality Therapy , Radiofrequency Ablation , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Gastrointestinal Neoplasms/drug therapy , Chemoembolization, Therapeutic/methods , Treatment Outcome
15.
Pathologie (Heidelb) ; 45(3): 223-232, 2024 May.
Article De | MEDLINE | ID: mdl-38587549

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.


Gastrointestinal Stromal Tumors , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/therapy , Humans , Protein Kinase Inhibitors/therapeutic use , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/drug therapy , Antineoplastic Agents/therapeutic use , Proto-Oncogene Proteins c-kit/genetics
16.
Mol Cancer ; 23(1): 67, 2024 04 01.
Article En | MEDLINE | ID: mdl-38561768

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.


Exosomes , Gastrointestinal Neoplasms , Humans , Exosomes/pathology , Biomarkers, Tumor , Biomarkers , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Liquid Biopsy/methods
17.
J Gastrointest Surg ; 28(4): 538-547, 2024 Apr.
Article En | MEDLINE | ID: mdl-38583908

BACKGROUND: With the development of endoscopic technology, endoscopic submucosal dissection (ESD) has been widely used in the treatment of gastrointestinal tumors. It is necessary to evaluate the depth of tumor invasion before the application of ESD. The convolution neural network (CNN) is a type of artificial intelligence that has the potential to assist in the classification of the depth of invasion in endoscopic images. This meta-analysis aimed to evaluate the performance of CNN in determining the depth of invasion of gastrointestinal tumors. METHODS: A search on PubMed, Web of Science, and SinoMed was performed to collect the original publications about the use of CNN in determining the depth of invasion of gastrointestinal neoplasms. Pooled sensitivity and specificity were calculated using an exact binominal rendition of the bivariate mixed-effects regression model. I2 was used for the evaluation of heterogeneity. RESULTS: A total of 17 articles were included; the pooled sensitivity was 84% (95% CI, 0.81-0.88), specificity was 91% (95% CI, 0.85-0.94), and the area under the curve (AUC) was 0.93 (95% CI, 0.90-0.95). The performance of CNN was significantly better than that of endoscopists (AUC: 0.93 vs 0.83, respectively; P = .0005). CONCLUSION: Our review revealed that CNN is one of the most effective methods of endoscopy to evaluate the depth of invasion of early gastrointestinal tumors, which has the potential to work as a remarkable tool for clinical endoscopists to make decisions on whether the lesion is feasible for endoscopic treatment.


Endoscopic Mucosal Resection , Gastrointestinal Neoplasms , Humans , Artificial Intelligence , Gastrointestinal Neoplasms/surgery , Gastrointestinal Neoplasms/pathology , Endoscopy, Gastrointestinal/methods , Neural Networks, Computer , Endoscopic Mucosal Resection/methods
18.
Biomed Pharmacother ; 174: 116574, 2024 May.
Article En | MEDLINE | ID: mdl-38593706

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies.


Cell Death , Gastrointestinal Neoplasms , Metals , Humans , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/drug therapy , Animals , Cell Death/drug effects , Ferroptosis/drug effects , Ions/metabolism , Antineoplastic Agents/pharmacology
19.
J Geriatr Oncol ; 15(4): 101747, 2024 May.
Article En | MEDLINE | ID: mdl-38513310

INTRODUCTION: Muscle and adipose tissue measures can be quantified from routinely obtained computed tomography (CT) images and are predictors of chemotherapy-related toxicities and survival among patients with gastrointestinal (GI) malignancies. Most studies to date have consisted of predominantly White patients, and the role of body composition among minoritized racial groups is unknown. We examined racial differences in body composition and survival among patients with GI malignancies. MATERIALS AND METHODS: This was a prospective cohort study of patients with GI malignancies. Single slices of axial CT images from L3 segments were analyzed using Slice-O-Matic software. The skeletal muscle area (cm2) was divided by height to obtain the skeletal muscle index (SMI, cm2/m2). Skeletal muscle radiodensity (SMD) in Hounsfield units (HU) was used for muscle composition. We compared body composition parameters between non-Hispanic (NH)-White and NH-Black participants. Cox models were used to examine the impact of body composition on survival. We proposed new race-specific cutoffs for body composition using optimal stratification. RESULTS: Five hundred forty patients were included, of which 24% were NH-Black. In Cox models stratified by race, each 5 cm2/m2 decrease in SMI was associated with increase in risk of all-cause mortality in NH-Black patients (hazard ratio [HR] 1.25; 95% confidence interval [CI] 1.04-1.49 p = 0.02). With the existing cut points, neither sarcopenia nor myosteatosis was associated with worse survival. Using a new cutoff for sarcopenia in NH-Black patients, NH-Black patients with sarcopenia (HR 2.31 95%CI 1.10-4.88 p = 0.03) and myosteatosis (HR 2.63 95% CI 1.25-5.53 p = 0.01) had worse survival. DISCUSSION: NH-Black older patients with GI cancers and sarcopenia or myosteatosis have worse overall survival.


Body Composition , Gastrointestinal Neoplasms , Tomography, X-Ray Computed , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Black or African American/statistics & numerical data , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/ethnology , Gastrointestinal Neoplasms/pathology , Muscle, Skeletal/diagnostic imaging , Proportional Hazards Models , Prospective Studies , Sarcopenia/ethnology , Sarcopenia/diagnostic imaging , White
20.
Pediatr Dev Pathol ; 27(3): 228-234, 2024.
Article En | MEDLINE | ID: mdl-38512910

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.


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/metabolism
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