Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.276
Filtrar
2.
BMC Cancer ; 24(1): 668, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824512

RESUMO

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.


Assuntos
Neoplasias Gastrointestinais , Humanos , Espanha/epidemiologia , Pessoa de Meia-Idade , Masculino , Feminino , Idoso , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/diagnóstico , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Adulto , Idade de Início , Estilo de Vida , Adenocarcinoma/epidemiologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Microambiente Tumoral , Qualidade de Vida , Incidência , Biomarcadores Tumorais , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia
3.
Am J Gastroenterol ; 119(6): 1056-1065, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38832708

RESUMO

INTRODUCTION: Ultra-processed food (UPF) intake has been associated with a higher risk of obesity, hypertension, type 2 diabetes, and cardiovascular diseases. The initial data on the relationship between UPF consumption and cancer risk were derived from retrospective observational studies with conflicting results. This systematic review and meta-analysis of prospective cohort studies aimed to investigate the association between UPF consumption and gastrointestinal cancer risk. METHODS: PubMed, Embase, and Cochrane databases were searched for prospective cohort studies that compared the highest vs the lowest level of UPF consumption according to NOVA food classification and reported the risk of gastrointestinal cancers by subsite. The association with cancer was quantified as hazard ratios (HR) using a random-effects model. RESULTS: Five prospective cohort studies were included in this review comprising 1,128,243 participants (241,201 participants in the highest and 223,366 in the lowest levels of UPF consumption). The mean follow-up ranged from 5.4 to 28 years. The highest UPF consumption was significantly associated with an increased risk of colorectal cancer (HR 1.11; 95% confidence interval [CI] 1.03-1.21; P = 0.01; I2 = 31%), colon cancer (HR 1.12; 95% CI 1.02-1.23; P = 0.02; I2 = 0%), and non-cardia gastric cancer (HR 1.43; 95% CI 1.02-2.00; P = 0.04; I2 = 0%) compared with the lowest UPF intake. However, no association was found between high UPF consumption and hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer. DISCUSSION: The highest level of UPF consumption was significantly associated with colorectal and non-cardia gastric cancer.


Assuntos
Fast Foods , Neoplasias Gastrointestinais , Humanos , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/etiologia , Fast Foods/efeitos adversos , Fatores de Risco , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/etiologia , Alimento Processado
4.
J Bodyw Mov Ther ; 39: 654-665, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38876699

RESUMO

OBJECTIVE: To investigate the effects of combined exercise on fatigue, anxiety, depression, quality of life and physical functioning in gastroinstestinal neoplasm in people under chemotherapy with oxaliplatin treatment. METHODS: We searched pubmed/MEDLINE, Cochrane Central Register of Controlled Trials, PEDro data base, and SciELO (until Nov 2023) for randomized controlled trials that investigated the effects of combined exercise in gastroinstestinal neoplasm people under chemotherapy with oxaliplatin treatment. Two comparisons were made: combined exercise versus usual care, combined aerobic and versus usual care (follow up). The main outcomes were muscle strength, aerobic capacity, fatigue, anxiety, depression and quality of life. Mean differences (MD) with 95% confidence interval (CI) were calculated. RESULTS: Seven randomized controlled trials met the eligibility criteria, which included 464 people. Compared to usual care, combined aerobic and resistance resulted in decrease of general fatigue (-2.82; IC: 4.92 to -0.69, N = 48), physical fatigue (-5.08; IC: 8.41 to -1.74, N = 48) and improvement of domain physical functioning of quality of life (9.40; IC: 2.74 to 16.06, N = 48). Compared to usual care, combined aerobic and resistance - Follow up resulted in decrease of general fatigue (-2.32; IC: 4.41 to - 0.28, N = 48), physical fatigue (-0.92; IC: 3.31 to -1.47, N = 48) and improvement ofdomain physical functioning of (9.83; IC: 0.66 to 19.01, N = 48). CONCLUSIONS: Our results demonstrate that combined exercises improves fatigue (general; physical), domain physical functioning of quality of life in gastrointestinal neoplasm people under chemotherapy treatment when compared to usual care.


Assuntos
Antineoplásicos , Terapia por Exercício , Fadiga , Oxaliplatina , Qualidade de Vida , Humanos , Fadiga/terapia , Oxaliplatina/administração & dosagem , Antineoplásicos/efeitos adversos , Terapia por Exercício/métodos , Força Muscular/fisiologia , Depressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Ansiedade , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/psicologia
5.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 598-604, 2024 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-38825906

RESUMO

Objective: To investigate the clinicopathological, immunophenotypic and molecular genetic characteristics, and differential diagnosis of NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) in the gastrointestinal tract. Methods: Two NTRK-RSCNs diagnosed at the Department of Pathology of the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China and one case diagnosed at Zhengzhou Central Hospital, Zhengzhou, China from 2019 to 2022 were collected. The clinical data, histopathology, immunophenotypes and prognosis were analyzed. Fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS) were used to detect NTRK gene rearrangements, while relevant literature was also reviewed and discussed. Results: Two patients were male and one was female, with the age of 17, 47 and 62 years, respectively. The tumors were located in the duodenum, ascending colon and descending colon, respectively. The tumors were protuberant masses with gray and rubbery sections. Their maximum diameter was 2.5, 5.0 and 10.0 cm, respectively. Histologically, the tumors invaded mucosa, intrinsic muscle and serosal adipose tissue. Tumor cells consisted of spindle or oval shaped cells with monotonous morphology and arranged in bundles or stripes pattern. Spindle cells were mildly to moderately atypical, with slightly eosinophilic cytoplasm and inconspicuous nucleoli. Necrosis and mitotic figures were observed in one high-grade tumor. All tumors expressed CD34, S-100 and pan-TRK in varying degrees. FISH analysis showed that NTRK1 gene was break-apart in 1 case and NTRK2 gene break-apart in 2 cases. NGS technologies showed LMNA::NTRK1 fusion in one case, STRN::NTRK2 fusion in another case. All patients recovered well after the surgery without recurrence at the end of the follow-up. Conclusions: NTRK-RSCN is rarely diagnosed in the gastrointestinal tract and has significant variations in morphology. It overlaps with various other mesenchymal tumors which should be considered as differential diagnoses. Be familiar with the features of histological morphology in combination with immunophenotype and molecular genetic characteristics can not only help diagnose NTRK-RSCNs, but provide therapeutic targets for clinical treatment.


Assuntos
Neoplasias Gastrointestinais , Hibridização in Situ Fluorescente , Receptor trkA , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Receptor trkA/genética , Receptor trkA/metabolismo , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Adolescente , Rearranjo Gênico , Diagnóstico Diferencial , Sequenciamento de Nucleotídeos em Larga Escala , Receptor trkB/genética , Receptor trkB/metabolismo
6.
Rev Prat ; 74(5): 537-541, 2024 May.
Artigo em Francês | MEDLINE | ID: mdl-38833239

RESUMO

MANAGEMENT OF GASTROINTESTINAL STROMAL TUMORS. Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma subtype. More than 80% of GIST are characterized by activating mutations in KIT or PDGFRA genes, but rare molecular subtypes exist. Localized GIST can be cured by surgery. Adjuvant treatment with imatinib is the gold standard in high-risk GIST presenting mutations sensitive to this tyrosine kinase inhibitor. The development of tyrosine kinase inhibitors targeting KIT and PDGFRA has revolutionized the prognosis of metastatic GIST, by increasing the median overall survival: from less than 18 months to more than 70 months within 20 years. Similary to other histological subtypes, the diagnostic and therapeutic management of GIST must be referred to sarcoma reference centers.


PRISE EN CHARGE DES TUMEURS STROMALES GASTRO-INTESTINALES. Les tumeurs stromales gastro-intestinales (GIST) représentent le sous-type de sarcomes le plus fréquent. Plus de 80 % des GIST sont caractérisées par des mutations activatrices des gènes KIT ou PDGFRA, mais des soustypes moléculaires plus rares existent. Au stade localisé, les GIST sont des maladies curables par exérèse chirurgicale. Le traitement adjuvant par imatinib est un standard thérapeutique dans les GIST associées à un haut risque de récidive et présentant des mutations sensibles au traitement. Au stade métastatique, le développement des inhibiteurs de tyrosine kinase ciblant KIT et PDGFRA a bouleversé la prise en charge et le pronostic des patients, en augmentant la survie globale : de moins de dix-huit mois il y a une vingtaine d'années à plus de soixante-dix mois aujourd'hui. Comme pour les autres sous-types histologiques, la prise en charge diagnostique et thérapeutique des GIST doit être réalisée dans des centres experts pour la prise en charge des sarcomes.


Assuntos
Tumores do Estroma Gastrointestinal , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Humanos , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/diagnóstico , Mesilato de Imatinib/uso terapêutico , Antineoplásicos/uso terapêutico
8.
Support Care Cancer ; 32(7): 432, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874678

RESUMO

PURPOSE: Upper gastrointestinal (GI) cancers contribute to 16.7% of UK cancer deaths. These patients make high use of acute hospital services, but detail about palliative care use is lacking. We aimed to determine the patterns of use of acute hospital and hospital specialist palliative care services in patients with advanced non-curative upper GI cancer. METHODS: We conducted a service evaluation of hospital use and palliative care for all patients with non-curative upper GI cancer seen in one large hospital, using routinely collected data (2019-2022). We report and characterise hospital admissions and palliative care within the study time period, using descriptive statistics, and multivariable Poisson regression to estimate the unadjusted and adjusted incidence rate ratio of hospital admissions. RESULTS: The total with non-curative upper GI cancer was 960. 86.7% had at least one hospital admission, with 1239 admissions in total. Patients had a higher risk of admission to hospital if: aged ≤ 65 (IRR for 66-75 years 0.71, IRR 76-85 years 0.68; IRR > 85 years 0.53; p < 0.05), or lived in an area of lower socioeconomic status (IMD Deciles 1-5) (IRR 0.90; p < 0.05). Over the 4-year period, the rate of re-admission was higher in patients not referred to palliative care (rate 0.52 readmissions/patient versus rate 1.47 readmissions/patient). CONCLUSION: People with advanced non-curative gastrointestinal cancer have frequent hospital admissions, especially if younger or from areas of lower socioeconomic status. There is clear association between specialist palliative care referral and reduced risk of hospitalisation. This evidence supports referral to specialist palliative care.


Assuntos
Neoplasias Gastrointestinais , Hospitalização , Cuidados Paliativos , Humanos , Cuidados Paliativos/estatística & dados numéricos , Cuidados Paliativos/métodos , Idoso , Masculino , Feminino , Idoso de 80 Anos ou mais , Neoplasias Gastrointestinais/terapia , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Reino Unido , Adulto
9.
Mol Biol Rep ; 51(1): 741, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874869

RESUMO

Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/ß-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.


Assuntos
Neoplasias Gastrointestinais , Ficocianina , Humanos , Ficocianina/farmacologia , Ficocianina/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/metabolismo
10.
BMC Gastroenterol ; 24(1): 197, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877387

RESUMO

BACKGROUND: Innate/adaptive immunity is the key to anti-tumor therapy. However, its causal relationship to Gastrointestinal (GI) cancer remains unclear. METHODS: Immunity genes were extracted from the MSigDB database. The Genome-wide association studies (GWAS) summary data of GI cancer were integrated with expression quantitative trait loci (eQTL) and DNA methylation quantitative trait loci (mQTL) associated with genes. Summary-data-based Mendelian randomization (SMR) and co-localization analysis were used to reveal causal relationships between genes and GI cancer. Two-sample MR analysis was used for sensitivity analysis. Single cell analysis clarified the enrichment of genes. RESULTS: Three-step SMR analysis showed that a putative mechanism, cg17294865 CpG site regulating HLA-DRA expression was negatively associated with gastric cancer risk. HLA-DRA was significantly differentially expressed in monocyte/macrophage and myeloid cells in gastric cancer. CONCLUSION: This study provides evidence that upregulating the expression level of HLA-DRA can reduce the risk of gastric cancer.


Assuntos
Imunidade Adaptativa , Metilação de DNA , Neoplasias Gastrointestinais , Estudo de Associação Genômica Ampla , Imunidade Inata , Análise da Randomização Mendeliana , Locos de Características Quantitativas , Humanos , Imunidade Inata/genética , Imunidade Adaptativa/genética , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/imunologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/imunologia , Cadeias alfa de HLA-DR/genética , Ilhas de CpG/genética , Multiômica
11.
Curr Opin Oncol ; 36(4): 282-290, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38726808

RESUMO

PURPOSE OF REVIEW: This review explores the role of circulating tumor (ct)DNA as a biomarker for clinical decision-making and monitoring purposes in metastatic gastrointestinal stromal tumor (GIST) patients. We discuss key insights from recent clinical trials and anticipate the future perspectives of ctDNA profiling within the clinical landscape of GIST. RECENT FINDINGS: The identification and molecular characterization of KIT/platelet-derived growth factor receptor alpha (PDGFRA) mutations from ctDNA in metastatic GIST is feasible and reliable. Such identification through ctDNA serves as a predictor of clinical outcomes to tyrosine-kinase inhibitors (TKIs) in metastatic patients. Additionally, conjoined ctDNA analysis from clinical trials reveal the evolving mutational landscapes and increase in intratumoral heterogeneity across treatment lines. Together, this data positions ctDNA determination as a valuable tool for monitoring disease progression and guiding therapy in metastatic patients. These collective efforts culminated in the initiation of a ctDNA-based randomized clinical trial in GIST, marking a significant milestone in integrating ctDNA testing into the clinical care of GIST patients. SUMMARY: The dynamic field of ctDNA technologies is rapidly evolving and holds significant promise for research. Several trials have successfully validated the clinical utility of ctDNA in metastatic GIST, laying the foundations for its prospective integration into the routine clinical management of GIST patients.


Assuntos
DNA Tumoral Circulante , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/sangue , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Inibidores de Proteínas Quinases/uso terapêutico , Mutação , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
Curr Opin Oncol ; 36(4): 308-312, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38726797

RESUMO

PURPOSE OF REVIEW: Claudins, components of tight cell junctions in epithelial and endothelial cells, have emerged as a therapeutic target in gastrointestinal (GI) malignancies, particularly claudin 18.2 (CLDN18.2). RECENT FINDINGS: Zolbetuximab, a chimeric anti-CLDN18.2 monoclonal antibody (mAb), is currently under FDA review and may emerge as the first claudin targeted therapy approved. Phase 3 trials show that zolbetuximab in combination with front-line fluoropyrimidine plus oxaliplatin improves survival in advanced CLDN18.2 positive (≥75% of tumor cells) gastric adenocarcinoma (GAC) patients. Many other therapies (mAbs; CART; bispecific; ADCs) are under investigation. SUMMARY: CLDN18.2 will be an important target in GAC. Early understanding of how to target CLDN18.2 based on the level of expression (high, moderate, low) will be the key to success in this area. Studying these as separate entities should be considered. Resistance patterns, loss of CLDN18.2 expression, role in the refractory setting, and if any role in localized disease are questions that remain. Other targets for claudin that target claudin six and four are under investigation. Their role in GI malignancies will soon be further clarified.


Assuntos
Claudinas , Neoplasias Gastrointestinais , Humanos , Claudinas/antagonistas & inibidores , Claudinas/metabolismo , Ensaios Clínicos Fase III como Assunto , Neoplasias Gastrointestinais/tratamento farmacológico , Terapia de Alvo Molecular
13.
Curr Opin Oncol ; 36(4): 313-319, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38726828

RESUMO

PURPOSE OF REVIEW: Overall, the review underscores the evolving landscape of KRAS-targeted therapy and the potential for these approaches to improve outcomes for patients with gastrointestinal malignancies. It highlights the importance of ongoing research and clinical trials in advancing precision medicine strategies for KRAS-driven cancers. This review provides a comprehensive overview of the RAS signaling pathway and its significance in gastrointestinal malignancies. RECENT FINDINGS: The introduction of KRAS inhibitor represents a significant advancement in the treatment landscape for KRAS-mutant cancers. In this review, we discuss upcoming trends in KRAS-targeted therapy, including the development of mutant-specific direct KRAS inhibitors like MRTX1133 and pan-RAS inhibitors such as RMC-6236. It also explores indirect RAS inhibitors targeting upstream and downstream components of the RAS pathway. Additionally, the review examines other upcoming strategies like combination therapies, such as CDK4/6 and ERK MAPK inhibitors, as well as adoptive cell therapy and cancer vaccines targeting KRAS-mutant cancers. SUMMARY: Targeting RAS has become an important strategy in treating gastrointestinal cancer. These findings in this review underscore the importance of a multidisciplinary approach, integrating advances in molecular profiling, targeted therapy, immunotherapy, and clinical research to optimize treatment strategies for patients with KRAS-mutant gastrointestinal malignancies.


Assuntos
Neoplasias Gastrointestinais , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/terapia , Neoplasias Gastrointestinais/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Terapia de Alvo Molecular , Mutação
14.
Curr Opin Oncol ; 36(4): 320-325, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38726837

RESUMO

PURPOSE OF REVIEW: This review is timely and relevant due to the increasing recognition of the significance of the fibroblast growth factor receptor (FGFR) family in cancer biology. Understanding the role of FGFRs and their dysregulation in various cancers is crucial for developing targeted therapies and improving patient outcomes. RECENT FINDINGS: The review highlights the importance of the FGFR family in cellular processes such as growth, proliferation, and survival. It discusses how abnormalities in FGFR2, including overexpression, gene amplification, and other genetic alterations, contribute to cancer progression, particularly in gastro-intestinal cancers. The paper also emphasizes the promising results of FGFR-targeted therapies, especially tyrosine kinase inhibitors, in certain cancers such as cholangiocarcinoma and oesophagogastric cancers. SUMMARY: The findings underscore the potential of FGFR-targeted therapies in treating cancers with FGFR dysregulation. However, the review also addresses the challenges associated with these therapies, including toxicities and mechanisms of resistance. Understanding these complexities is essential for optimizing the efficacy of FGFR-targeted treatments and improving patient outcomes in clinical practice and research efforts.


Assuntos
Neoplasias Gastrointestinais , Receptores de Fatores de Crescimento de Fibroblastos , Humanos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Receptores de Fatores de Crescimento de Fibroblastos/antagonistas & inibidores , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Terapia de Alvo Molecular , Inibidores de Proteínas Quinases/uso terapêutico , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/antagonistas & inibidores , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia
15.
Sci Rep ; 14(1): 12415, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816560

RESUMO

Gastrointestinal stromal tumors (GISTs) are a rare type of tumor that can develop liver metastasis (LIM), significantly impacting the patient's prognosis. This study aimed to predict LIM in GIST patients by constructing machine learning (ML) algorithms to assist clinicians in the decision-making process for treatment. Retrospective analysis was performed using the Surveillance, Epidemiology, and End Results (SEER) database, and cases from 2010 to 2015 were assigned to the developing sets, while cases from 2016 to 2017 were assigned to the testing set. Missing values were addressed using the multiple imputation technique. Four algorithms were utilized to construct the models, comprising traditional logistic regression (LR) and automated machine learning (AutoML) analysis such as gradient boost machine (GBM), deep neural net (DL), and generalized linear model (GLM). We evaluated the models' performance using LR-based metrics, including the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA), as well as AutoML-based metrics, such as feature importance, SHapley Additive exPlanation (SHAP) Plots, and Local Interpretable Model Agnostic Explanation (LIME). A total of 6207 patients were included in this study, with 2683, 1780, and 1744 patients allocated to the training, validation, and test sets, respectively. Among the different models evaluated, the GBM model demonstrated the highest performance in the training, validation, and test cohorts, with respective AUC values of 0.805, 0.780, and 0.795. Furthermore, the GBM model outperformed other AutoML models in terms of accuracy, achieving 0.747, 0.700, and 0.706 in the training, validation, and test cohorts, respectively. Additionally, the study revealed that tumor size and tumor location were the most significant predictors influencing the AutoML model's ability to accurately predict LIM. The AutoML model utilizing the GBM algorithm for GIST patients can effectively predict the risk of LIM and provide clinicians with a reference for developing individualized treatment plans.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Hepáticas , Aprendizado de Máquina , Programa de SEER , Humanos , Tumores do Estroma Gastrointestinal/patologia , Neoplasias Hepáticas/secundário , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Prognóstico , Adulto , Algoritmos , Curva ROC , Neoplasias Gastrointestinais/patologia
16.
J Transl Med ; 22(1): 429, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711123

RESUMO

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.


Assuntos
Gastrite Atrófica , Neoplasias Gastrointestinais , Humanos , Gastrite Atrófica/complicações , Gastrite Atrófica/epidemiologia , Fatores de Risco , Neoplasias Gastrointestinais/epidemiologia , Neoplasias Gastrointestinais/patologia , Doença Crônica , Incidência , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Masculino , Razão de Chances , Feminino , Viés de Publicação
17.
J Med Internet Res ; 26: e51059, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758583

RESUMO

BACKGROUND: Patients with advanced cancer undergoing chemotherapy experience significant symptoms and declines in functional status, which are associated with poor outcomes. Remote monitoring of patient-reported outcomes (PROs; symptoms) and step counts (functional status) may proactively identify patients at risk of hospitalization or death. OBJECTIVE: The aim of this study is to evaluate the association of (1) longitudinal PROs with step counts and (2) PROs and step counts with hospitalization or death. METHODS: The PROStep randomized trial enrolled 108 patients with advanced gastrointestinal or lung cancers undergoing cytotoxic chemotherapy at a large academic cancer center. Patients were randomized to weekly text-based monitoring of 8 PROs plus continuous step count monitoring via Fitbit (Google) versus usual care. This preplanned secondary analysis included 57 of 75 patients randomized to the intervention who had PRO and step count data. We analyzed the associations between PROs and mean daily step counts and the associations of PROs and step counts with the composite outcome of hospitalization or death using bootstrapped generalized linear models to account for longitudinal data. RESULTS: Among 57 patients, the mean age was 57 (SD 10.9) years, 24 (42%) were female, 43 (75%) had advanced gastrointestinal cancer, 14 (25%) had advanced lung cancer, and 25 (44%) were hospitalized or died during follow-up. A 1-point weekly increase (on a 32-point scale) in aggregate PRO score was associated with 247 fewer mean daily steps (95% CI -277 to -213; P<.001). PROs most strongly associated with step count decline were patient-reported activity (daily step change -892), nausea score (-677), and constipation score (524). A 1-point weekly increase in aggregate PRO score was associated with 20% greater odds of hospitalization or death (adjusted odds ratio [aOR] 1.2, 95% CI 1.1-1.4; P=.01). PROs most strongly associated with hospitalization or death were pain (aOR 3.2, 95% CI 1.6-6.5; P<.001), decreased activity (aOR 3.2, 95% CI 1.4-7.1; P=.01), dyspnea (aOR 2.6, 95% CI 1.2-5.5; P=.02), and sadness (aOR 2.1, 95% CI 1.1-4.3; P=.03). A decrease in 1000 steps was associated with 16% greater odds of hospitalization or death (aOR 1.2, 95% CI 1.0-1.3; P=.03). Compared with baseline, mean daily step count decreased 7% (n=274 steps), 9% (n=351 steps), and 16% (n=667 steps) in the 3, 2, and 1 weeks before hospitalization or death, respectively. CONCLUSIONS: In this secondary analysis of a randomized trial among patients with advanced cancer, higher symptom burden and decreased step count were independently associated with and predictably worsened close to hospitalization or death. Future interventions should leverage longitudinal PRO and step count data to target interventions toward patients at risk for poor outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616768; https://clinicaltrials.gov/study/NCT04616768. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2021-054675.


Assuntos
Hospitalização , Medidas de Resultados Relatados pelo Paciente , Humanos , Pessoa de Meia-Idade , Masculino , Hospitalização/estatística & dados numéricos , Feminino , Idoso , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/mortalidade
19.
J Cancer Res Clin Oncol ; 150(5): 283, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806870

RESUMO

OBJECTIVE: The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors. METHODS: Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions. RESULTS: 1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05). CONCLUSION: Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients. CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Irinotecano , Náusea , Olanzapina , Oxaliplatina , Vômito , Humanos , Olanzapina/administração & dosagem , Olanzapina/uso terapêutico , Olanzapina/efeitos adversos , Feminino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Prospectivos , Oxaliplatina/efeitos adversos , Oxaliplatina/administração & dosagem , Irinotecano/efeitos adversos , Irinotecano/administração & dosagem , Idoso , Adulto , Antieméticos/administração & dosagem , Antieméticos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Palonossetrom/administração & dosagem , Palonossetrom/uso terapêutico , Qualidade de Vida , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico
20.
Cancer Treat Rev ; 128: 102752, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772170

RESUMO

Surgery is a standard treatment for early-stage gastrointestinal cancers, often preceded by neoadjuvant chemo(radio)therapy or followed by adjuvant therapy. While leading to cure in a proportion of patients, it has some drawbacks such as intra/post-operative complications, mutilation and life-long functional sequelae. Further to the unprecedented efficacy data from studies of immune checkpoint inhibitors for advanced mismatch repair deficient/microsatellite instable (dMMR/MSI-H) tumours, a strong interest has recently emerged for the investigation of such agents in the neoadjuvant setting. Although limited by the exploratory design and small sample size, trials of neoadjuvant immune checkpoint inhibitors for early-stage dMMR/MSI-H gastrointestinal cancers have consistently reported complete response rates ranging from 70 % to 100 %. As a result, the question has arisen as to whether surgery is still needed or organ-preserving strategies should be offered to this especially immuno-sensitive population. In this article, we discuss the available evidence for neoadjuvant immune checkpoint inhibitors in dMMR/MSI-H gastrointestinal cancers and analyse opportunities and challenges to the implementation of non-operative management approaches in this setting.


Assuntos
Neoplasias Gastrointestinais , Inibidores de Checkpoint Imunológico , Terapia Neoadjuvante , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/terapia , Terapia Neoadjuvante/métodos , Instabilidade de Microssatélites , Reparo de Erro de Pareamento de DNA
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...