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1.
Zhonghua Bing Li Xue Za Zhi ; 53(6): 598-604, 2024 Jun 08.
Article in Chinese | MEDLINE | ID: mdl-38825906

ABSTRACT

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.


Subject(s)
Gastrointestinal Neoplasms , In Situ Hybridization, Fluorescence , Receptor, trkA , Humans , Male , Female , Middle Aged , Receptor, trkA/genetics , Receptor, trkA/metabolism , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Adolescent , Gene Rearrangement , Diagnosis, Differential , High-Throughput Nucleotide Sequencing , Receptor, trkB/genetics , Receptor, trkB/metabolism
2.
BMC Cancer ; 24(1): 668, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824512

ABSTRACT

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.


Subject(s)
Gastrointestinal Neoplasms , Humans , Spain/epidemiology , Middle Aged , Male , Female , Aged , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/pathology , Gastrointestinal Neoplasms/therapy , Adult , Age of Onset , Life Style , Adenocarcinoma/epidemiology , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Tumor Microenvironment , Quality of Life , Incidence , Biomarkers, Tumor , Esophageal Neoplasms/epidemiology , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/pathology , Esophageal Neoplasms/therapy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology
3.
Am J Gastroenterol ; 119(6): 1056-1065, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38832708

ABSTRACT

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.


Subject(s)
Fast Foods , Gastrointestinal Neoplasms , Humans , Gastrointestinal Neoplasms/epidemiology , Gastrointestinal Neoplasms/etiology , Fast Foods/adverse effects , Risk Factors , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/etiology , Stomach Neoplasms/epidemiology , Stomach Neoplasms/etiology , Food, Processed
4.
Rev Prat ; 74(5): 537-541, 2024 May.
Article in French | MEDLINE | ID: mdl-38833239

ABSTRACT

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.


Subject(s)
Gastrointestinal Stromal Tumors , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/therapy , Humans , Gastrointestinal Neoplasms/therapy , Gastrointestinal Neoplasms/diagnosis , Imatinib Mesylate/therapeutic use , Antineoplastic Agents/therapeutic use
5.
PLoS One ; 19(5): e0302880, 2024.
Article in English | MEDLINE | ID: mdl-38718092

ABSTRACT

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.


Subject(s)
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
6.
Support Care Cancer ; 32(6): 329, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709308

ABSTRACT

BACKGROUND: Psychological distress is a prevalent unpleasant experience faced by many cancer patients. However, the psychological distress among gastrointestinal (GI) cancer patients is scarcely explored. Moreover, the association between psychological distress and quality of life in different genders has yet to be explored. AIMS: To explore the psychological distress among GI cancer patients and examine its association with quality of life among different genders. METHODS: This study was a cross-sectional study. A total of 237 gastrointestinal cancer patients completed the distress thermometer and the Functional Assessment of Chronic Illness Therapy-General. RESULTS: The mean score of psychological distress of the participants was 3.04 (SD = 2.90). A greater proportion of female gastrointestinal cancer patients (52.8%) had clinically relevant psychological distress compared to males (35.9%). The quality of life was negatively associated with their psychological distress (B = - 1.502, 95%CI: - 2.759 to - 0.245, p = 0.019) among gastrointestinal cancer patients. Such association was stronger among males compared to females in gastrointestinal cancer patients (Interaction term, B = - 1.713, 95%CI: - 3.123 to - 0.303, p = 0.017). CONCLUSIONS: These findings suggest that healthcare providers should attach their attention to gastrointestinal cancer patients' psychological distress, especially females. Longitudinal studies could adopted to track the changes in psychological distress and its association with quality of life over time among different genders. In future intervention studies, the focus of psychological interventions needs to be gender-specific.


Subject(s)
Gastrointestinal Neoplasms , Psychological Distress , Quality of Life , Humans , Male , Gastrointestinal Neoplasms/psychology , Female , Cross-Sectional Studies , Middle Aged , Sex Factors , Aged , Adult , Stress, Psychological/epidemiology , Stress, Psychological/etiology , Stress, Psychological/psychology , Surveys and Questionnaires
7.
Methods Cell Biol ; 186: 25-49, 2024.
Article in English | MEDLINE | ID: mdl-38705603

ABSTRACT

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.


Subject(s)
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
8.
Acta Oncol ; 63: 288-293, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712513

ABSTRACT

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.


Subject(s)
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
9.
Clin Adv Hematol Oncol ; 22(4): 162-173, 2024 May.
Article in English | MEDLINE | ID: mdl-38739719

ABSTRACT

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.


Subject(s)
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
10.
Front Immunol ; 15: 1381061, 2024.
Article in English | MEDLINE | ID: mdl-38774877

ABSTRACT

Background: Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs. Methods: We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model. Results: A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence. Conclusions: Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.


Subject(s)
Gastrointestinal Neoplasms , Immune Checkpoint Inhibitors , Neoplasm Staging , Humans , Female , Male , Gastrointestinal Neoplasms/immunology , Gastrointestinal Neoplasms/drug therapy , Middle Aged , Aged , Retrospective Studies , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Adult , Thyroid Gland/pathology , Thyroid Gland/immunology , Thyroid Gland/metabolism , Prognosis , Biomarkers, Tumor
12.
J Immunother Cancer ; 12(5)2024 May 23.
Article in English | MEDLINE | ID: mdl-38782539

ABSTRACT

Immune checkpoint inhibitors (ICIs) revolutionized the management of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers. Based on notable results observed in the metastatic setting, several clinical trials investigated ICIs as neoadjuvant treatment (NAT) for localized dMMR/MSI-H GI cancers, achieving striking results in terms of clinical and pathological responses and creating the opportunity to spare patients from neoadjuvant chemotherapy and/or radiotherapy and even surgical resection. Nevertheless, these impressive findings are mainly derived from small proof of concept phase II studies and there are still several open questions to address. Moreover, dMMR/MSI-H represents a limited subgroup accounting for less than 10% of GI cancers. Consequently, many efforts have been produced to investigate neoadjuvant ICIs also in mismatch repair-proficient/microsatellite stable (MSS) cancers, considering the potential synergistic effect in combining immune-targeted agents with standard therapies such as chemo and/or radiotherapy. However, results for combining ICIs to the standard of care in the unselected population are still unsatisfactory, without improvements in event-free survival in esophago-gastric adenocarcinoma for the addition of pembrolizumab to chemotherapy, and sometimes limited benefit in patients with locally advanced rectal cancer. Therefore, a major challenge will be to identify among the heterogenous spectrum of this disease, those patients that could take advantage of neoadjuvant immunotherapy and deliver the most effective treatment. In this review we discuss the rationale of NAT in GI malignancies, summarize the available evidence regarding the completed trials that evaluated this treatment strategy in both MSI-H and MSS tumors. Finally, we discuss ongoing studies and future perspectives to render neoadjuvant immunotherapy another arrow in the quiver for the treatment of locally advanced GI tumors.


Subject(s)
Gastrointestinal Neoplasms , Immunotherapy , Neoadjuvant Therapy , Humans , Neoadjuvant Therapy/methods , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/therapy , Immunotherapy/methods , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/pharmacology , Microsatellite Instability
13.
Curr Oncol ; 31(5): 2620-2635, 2024 05 05.
Article in English | MEDLINE | ID: mdl-38785478

ABSTRACT

Chinese patients face higher risks of gastrointestinal (GI) cancers and greater cancer-related deaths than Canadian-born patients. The older population encounters barriers to quality healthcare, impacting their well-being and survival. Previous studies highlighted Chinese immigrant perceptions of not requiring healthcare support. During the COVID-19 pandemic, their underutilization of healthcare services garnered attention. The present study explores the experiences of older Chinese cancer patients to improve culturally sensitive cancer care. A total of twenty interviews carried out in Cantonese and Mandarin were conducted with Chinese immigrants, aged 60 or above, diagnosed with Stage 3 or 4 GI cancer. These interviews were transcribed verbatim, translated, and subjected to qualitative descriptive analysis. Among older Chinese immigrant patients, a phenomenon termed "Premature Acceptance: Normalizing Death and Dying" was observed. This involved four key themes: 1. acceptance and letting go, 2. family first, 3. self-sufficiency, and 4. barriers to supportive care. Participants displayed an early acceptance of their own mortality, prioritizing family prosperity over their own quality of life. Older Chinese patients normalize the reality of facing death amidst cancer. They adopt a pragmatic outlook, acknowledging life-saving treatments while willingly sacrificing their own support needs to ease family burdens. Efforts to enhance health literacy require culturally sensitive programs tailored to address language barriers and differing values among this population. A strengths-based approach emphasizing family support and practical aspects of care may help build resilience and improve symptom management, thereby enhancing their engagement with healthcare services.


Subject(s)
COVID-19 , Humans , Aged , Female , Male , Middle Aged , COVID-19/psychology , Aged, 80 and over , China , Emigrants and Immigrants/psychology , Gastrointestinal Neoplasms/psychology , Canada , Asian People/psychology , Attitude to Death , Neoplasms/psychology , Neoplasms/mortality , Qualitative Research , SARS-CoV-2 , East Asian People
14.
PLoS One ; 19(5): e0304574, 2024.
Article in English | MEDLINE | ID: mdl-38814898

ABSTRACT

BACKGROUND: The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer). METHODS: We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions. RESULTS: We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors. CONCLUSIONS: The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.


Subject(s)
Gastrointestinal Neoplasms , Genome-Wide Association Study , Mendelian Randomization Analysis , Metabolome , Humans , Gastrointestinal Neoplasms/blood , Gastrointestinal Neoplasms/genetics , Male , Female , Finland/epidemiology , Carnitine/blood , Carnitine/analogs & derivatives , Middle Aged , Risk Factors , Liver Neoplasms/blood , Liver Neoplasms/genetics
15.
J Transl Med ; 22(1): 429, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711123

ABSTRACT

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.


Subject(s)
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
16.
J Med Internet Res ; 26: e51059, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758583

ABSTRACT

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.


Subject(s)
Hospitalization , Patient Reported Outcome Measures , Humans , Middle Aged , Male , Hospitalization/statistics & numerical data , Female , Aged , Neoplasms/drug therapy , Neoplasms/mortality , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/mortality
17.
Abdom Radiol (NY) ; 49(5): 1716-1733, 2024 May.
Article in English | MEDLINE | ID: mdl-38691132

ABSTRACT

There is a diverse group of non-gastrointestinal stromal tumor (GIST), mesenchymal neoplasms of the gastrointestinal (GI) tract that demonstrate characteristic pathology and histogenesis as well as variable imaging findings and biological behavior. Recent advancements in tumor genetics have unveiled specific abnormalities associated with certain tumors, influencing their molecular pathogenesis, biology, response to treatment, and prognosis. Notably, giant fibrovascular polyps of the esophagus, identified through MDM2 gene amplifications, are now classified as liposarcomas. Some tumors exhibit distinctive patterns of disease distribution. Glomus tumors and plexiform fibromyxomas exhibit a pronounced affinity for the gastric antrum. In contrast, smooth muscle tumors within the GI tract are predominantly found in the esophagus and colorectum, surpassing the incidence of GISTs in these locations. Surgical resection suffices for symptomatic benign tumors; multimodality treatment may be necessary for frank sarcomas. This article aims to elucidate the cross-sectional imaging findings associated with a wide spectrum of these tumors, providing insights that align with their histopathological features.


Subject(s)
Gastrointestinal Neoplasms , Humans , Gastrointestinal Neoplasms/diagnostic imaging , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/genetics , Gastrointestinal Stromal Tumors/pathology , Diagnostic Imaging/methods
18.
Sci Rep ; 14(1): 12415, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38816560

ABSTRACT

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.


Subject(s)
Gastrointestinal Stromal Tumors , Liver Neoplasms , Machine Learning , SEER Program , Humans , Gastrointestinal Stromal Tumors/pathology , Liver Neoplasms/secondary , Male , Female , Middle Aged , Retrospective Studies , Aged , Prognosis , Adult , Algorithms , ROC Curve , Gastrointestinal Neoplasms/pathology
19.
Asian Pac J Cancer Prev ; 25(5): 1725-1735, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38809645

ABSTRACT

BACKGROUND: Gastrointestinal (GI) cancer burden in Asia is increasing, and Vietnam is no exception. Assessing the affordability of achieving a quality-adjusted life year (QALY) in gastrointestinal cancer patients Vietnam, as well as identifying predictors of willingness to pay (WTP) per QALY, is crucial to decision-making around medical intervention prioritization and performing medical technology assessments for these cancers. OBJECTIVES: Our study aimed to estimate WTP/QALY gained and associated factors among patients diagnosed with GI cancer at a tertiary hospital in Hue, Vietnam. METHODS: A cross-sectional descriptive study, using contingent valuation methodology was conducted among 231 patients at tertiary hospital in 2022. A double limited dichotomous choice and the EQ-5D-5L were utilised to estimate WTP and QALY, respectively. Quantile regression was applied to determine predictors of WTP/QALY. RESULTS: The mean and median maximum WTP/QALY gained among GI patients was $15,165.6 (42,239.6) and $4,365.6 (IQR: 1,586.5-14,552.0), respectively, which was equal to 3.68 times the 2022 gross domestic product (GDP) per capita in Vietnam.  Additionally, cancer severity was found to have a significant impact  on WTP per QALY gained, with a higher amount identified among patients with earlier stages of GI cancer. Furthermore, living in an urban dwelling and patients' treatment modalities were significantly associated with WTP/QALY. CONCLUSION: Evidence from our study can be used to inform how decision-makers in Vietnam to determine the cost-effectiveness of GI cancer interventions.


Subject(s)
Gastrointestinal Neoplasms , Quality-Adjusted Life Years , Tertiary Care Centers , Humans , Gastrointestinal Neoplasms/economics , Gastrointestinal Neoplasms/psychology , Gastrointestinal Neoplasms/therapy , Male , Tertiary Care Centers/economics , Female , Cross-Sectional Studies , Vietnam , Middle Aged , Aged , Cost-Benefit Analysis , Prognosis , Follow-Up Studies , Quality of Life , Adult
20.
J Cancer Res Clin Oncol ; 150(5): 283, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38806870

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Irinotecan , Nausea , Olanzapine , Oxaliplatin , Vomiting , Humans , Olanzapine/administration & dosage , Olanzapine/therapeutic use , Olanzapine/adverse effects , Female , Middle Aged , Nausea/chemically induced , Nausea/prevention & control , Vomiting/chemically induced , Vomiting/prevention & control , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Prospective Studies , Oxaliplatin/adverse effects , Oxaliplatin/administration & dosage , Irinotecan/adverse effects , Irinotecan/administration & dosage , Aged , Adult , Antiemetics/administration & dosage , Antiemetics/therapeutic use , Gastrointestinal Neoplasms/drug therapy , Palonosetron/administration & dosage , Palonosetron/therapeutic use , Quality of Life , Dexamethasone/administration & dosage , Dexamethasone/therapeutic use
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