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1.
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
2.
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
3.
Support Care Cancer ; 32(6): 329, 2024 May 06.
Article En | MEDLINE | ID: mdl-38709308

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.


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
4.
J Cancer Res Clin Oncol ; 150(5): 283, 2024 May 28.
Article En | MEDLINE | ID: mdl-38806870

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.


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
5.
Braz J Med Biol Res ; 57: e13344, 2024.
Article En | MEDLINE | ID: mdl-38808887

Reminiscence therapy (RT) attenuates psychological disorders in cancer patients. This study aimed to evaluate the effect of RT on anxiety, depression, spiritual well-being, and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer. A total of 222 elderly patients with unresectable, metastatic gastrointestinal cancer were randomized into RT group (RT plus usual care, n=112) or control group (usual care, n=110) with a 6-month intervention. Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), and Quality of Life Questionnaire-Core 30 (QLQ-C30) were evaluated at month (M)0, M1, M3, and M6. Concerning the primary outcome, HADS-A score at M6 decreased in the RT group compared to the control group (P=0.005). As to secondary outcomes, the RT group showed decreased HADS-A scores at M3, anxiety rate at M3, HADS-D scores at M3 and M6, depression rate at M6, as well as greater FACIT-Sp scores at M1, M3, and M6 vs the control group (all P<0.050). Additionally, QLQ-C30 global health score was elevated at M1 (P=0.046) and M6 (P=0.005), functions score was greater at M6 (P=0.038), and symptoms score was lower at M3 (P=0.019) in the RT group than in the control group. Subgroup analysis revealed that the addition of RT was more effective for patients with anxiety or depression at baseline. In summary, RT alleviated anxiety and depression, and improved the spiritual well-being and quality of life within 6 months in elderly patients with unresectable, metastatic gastrointestinal cancer.


Anxiety , Depression , Gastrointestinal Neoplasms , Mental Health , Quality of Life , Humans , Male , Female , Gastrointestinal Neoplasms/psychology , Gastrointestinal Neoplasms/therapy , Aged , Anxiety/therapy , Depression/therapy , Treatment Outcome , Surveys and Questionnaires , Middle Aged , Aged, 80 and over , Psychiatric Status Rating Scales , Psychotherapy/methods
6.
Front Immunol ; 15: 1381061, 2024.
Article En | MEDLINE | ID: mdl-38774877

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.


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
8.
PLoS One ; 19(5): e0302964, 2024.
Article En | MEDLINE | ID: mdl-38776289

BACKGROUND: Iron deficiency anemia (IDA) is a prevalent hematological complication associated with gastrointestinal (GI) cancers due to an increased loss of iron and decreased iron absorption. The purpose of this systematic review is to evaluate the use of parenteral iron to treat IDA in patients with GI cancer. METHODS: PubMed, Cochrane, EMBASE, CINHAL and Scopus were searched from January 1, 2010 to September 29, 2023 with no language restrictions. We excluded editorials, case reports, abstracts, conference papers, and poster presentations. Studies were included if they discussed IDA, GI neoplasms, use of iron supplementation (with or without erythropoietin-stimulating agents [ESAs]), defined anemia and had an adult patient population. We assessed the efficacy of parenteral iron in comparison to other iron supplementation methods when treating IDA in patients with GI cancer. The Cochrane Risk of Bias Tool 2 (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) assessment tools were used to assess the quality of the included studies. Moreover, the Cochrane Effective Practice and Organization data collection form was used to collect pertinent study information. RESULTS: Our search yielded 3,969 studies across all databases. Twenty-one studies were included (6 randomized control trials; 15 non-randomized studies). Of the 15 studies evaluating hemoglobin (Hb) response, seven studies found an increase in Hb levels when patients were treated with IV iron. The 14 studies evaluating red blood cell (RBC) transfusion rates found conflicting differences in RBC transfusion needs when treated with IV iron. Studies analyzing health related outcomes typically found an increase in quality of life and decreased post-operative complications. DISCUSSION: This review demonstrates improved outcomes of IDA in patients with GI cancer treated with IV iron instead of other iron supplementation methods. Timely diagnosis and appropriate IDA management can greatly improve quality of life in this patient population, especially if myelosuppressive chemotherapy is required.


Anemia, Iron-Deficiency , Gastrointestinal Neoplasms , Iron , Humans , Anemia, Iron-Deficiency/drug therapy , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/drug therapy , Iron/administration & dosage , Iron/therapeutic use , Administration, Intravenous
9.
J Med Internet Res ; 26: e51059, 2024 May 17.
Article En | MEDLINE | ID: mdl-38758583

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.


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
10.
PLoS One ; 19(5): e0303290, 2024.
Article En | MEDLINE | ID: mdl-38743680

Genike, the imatinib (IM)-alpha form is widely used in the treatment of gastrointestinal stromal tumor (GIST) patients in China. We wanted to investigate whether there are differences in IM plasma concentrations, adverse events, health-related quality of life (QOL) and outcomes between patients treated with Genike and Glivec. Thirty included GIST patients receiving IM treatment were matched to either Genike or Glivec according to gastrectomy, body weight, body surface area and sex. There was no statistically significant difference in IM trough plasma levels between the two groups. There were no significant differences in very common adverse events of IM between the Genike and Glivec groups. IM was well tolerated, although it was associated with a significant change in cognitive function (P < 0.001), fatigue (P = 0.015), pain (P = 0.015), nausea/vomiting (P = 0.029), insomnia (P = 0.019), diarrhea (P = 0.003) and financial difficulties (P < 0.001). Physical functioning, financial burden and insomnia were significantly different between the two groups (P = 0.026). Until Aug. 2022, there was no significant difference in time to imatinib treatment failure (TTF) between the two groups. In conclusion, there was no difference in IM plasma concentration and adverse events between Genike and Glivec. Both Genike and Glivec could partially decrease the QOL of GIST patients. Physical functioning was worse in Genike group than in Glivec group, while the economic burden and symptoms of insomnia in Glivec patients were worse. There was no significant difference in TTF between the two groups.


Antineoplastic Agents , Gastrointestinal Stromal Tumors , Imatinib Mesylate , Quality of Life , Humans , Gastrointestinal Stromal Tumors/drug therapy , Gastrointestinal Stromal Tumors/blood , Imatinib Mesylate/therapeutic use , Imatinib Mesylate/adverse effects , Female , Male , Middle Aged , Aged , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Adult , Treatment Outcome , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/blood , Case-Control Studies
11.
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
12.
Abdom Radiol (NY) ; 49(5): 1716-1733, 2024 May.
Article En | MEDLINE | ID: mdl-38691132

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.


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
13.
J Immunother Cancer ; 12(5)2024 May 23.
Article En | MEDLINE | ID: mdl-38782539

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.


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
14.
Curr Oncol ; 31(5): 2620-2635, 2024 05 05.
Article En | MEDLINE | ID: mdl-38785478

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.


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
15.
Int J Mol Sci ; 25(10)2024 May 13.
Article En | MEDLINE | ID: mdl-38791353

Acetylcholine-activated receptors are divided broadly into two major structurally distinct classes: ligand-gated ion channel nicotinic and G-protein-coupled muscarinic receptors. Each class encompasses several structurally related receptor subtypes with distinct patterns of tissue expression and post-receptor signal transduction mechanisms. The activation of both nicotinic and muscarinic cholinergic receptors has been associated with the induction and progression of gastrointestinal neoplasia. Herein, after briefly reviewing the classification of acetylcholine-activated receptors and the role that nicotinic and muscarinic cholinergic signaling plays in normal digestive function, we consider the mechanics of acetylcholine synthesis and release by neuronal and non-neuronal cells in the gastrointestinal microenvironment, and current methodology and challenges in measuring serum and tissue acetylcholine levels accurately. Then, we critically evaluate the evidence that constitutive and ligand-induced activation of acetylcholine-activated receptors plays a role in promoting gastrointestinal neoplasia. We focus primarily on adenocarcinomas of the stomach, pancreas, and colon, because these cancers are particularly common worldwide and, when diagnosed at an advanced stage, are associated with very high rates of morbidity and mortality. Throughout this comprehensive review, we concentrate on identifying novel ways to leverage these observations for prognostic and therapeutic purposes.


Acetylcholine , Gastrointestinal Neoplasms , Humans , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Acetylcholine/metabolism , Animals , Signal Transduction , Receptors, Muscarinic/metabolism , Receptors, Nicotinic/metabolism
16.
Pathol Res Pract ; 258: 155289, 2024 Jun.
Article En | MEDLINE | ID: mdl-38703607

Radiotherapy (RT) is a frequently used treatment for cervical cancer, effectively decreasing the likelihood of the disease returning in the same area and extending the lifespan of individuals with cervical cancer. Nevertheless, the primary reason for treatment failure in cancer patients is the cancer cells' resistance to radiation therapy (RT). Long non-coding RNAs (LncRNAs) are a subset of RNA molecules that do not code for proteins and are longer than 200 nucleotides. They have a significant impact on the regulation of gastrointestinal (GI) cancers biological processes. Recent research has shown that lncRNAs have a significant impact in controlling the responsiveness of GI cancer to radiation. This review provides a concise overview of the composition and operation of lncRNAs as well as the intricate molecular process behind radiosensitivity in GI cancer. Additionally, it compiles a comprehensive list of lncRNAs that are linked to radiosensitivity in such cancers. Furthermore, it delves into the potential practical implementation of these lncRNAs in modulating radiosensitivity in GI cancer.


Gastrointestinal Neoplasms , RNA, Long Noncoding , Radiation Tolerance , Humans , RNA, Long Noncoding/genetics , Gastrointestinal Neoplasms/radiotherapy , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Radiation Tolerance/genetics , Gene Expression Regulation, Neoplastic
17.
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
18.
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
19.
Pan Afr Med J ; 47: 107, 2024.
Article En | MEDLINE | ID: mdl-38766563

Introduction: Health-related quality of life (HRQoL) examines the impact of the symptoms of dyspepsia on the daily life of sufferers. There are a few published studies related to HRQoL of persons with dyspepsia in Africa. Methods: this was a hospital-based cross-sectional study involving 324 dyspeptic patients referred for upper gastrointestinal endoscopy to the University of Benin Teaching Hospitals (UBTH) The ROME IV criteria were used to recruit patients with dyspepsia. The short form Nepean Dyspepsia Index (SF NDI) was used to assess HRQoL in all participants. Upper gastrointestinal endoscopy was performed on all 324 dyspeptic patients. Results: the mean age of patients was 47.6 ± 15.6 years. Three hundred (92.6%) patients had significantly impaired HRQoL with an SF NDI mean score of 31.3 ± 9.1. Interference with daily activities and eating and drinking subdomains were more impaired than other subdomains of HRQoL (p < 0.001). There was no statistical difference between the impaired HRQoL in patients with functional dyspepsia and organic dyspepsia (p = 0.694). Among patients with organic dyspepsia, those with upper gastrointestinal cancers had significantly worse HRQoL SF NDI mean (sd) scores (39.7 ± 5.9) compared with patients with gastritis, peptic ulcer disease and GERD with (30.3 ± 9.2, 31.5 ± 9.7 and 32.9 ± 7.1 respectively) (p = 0.01). Conclusion: health-related quality of life is significantly impaired in patients with dyspepsia and those with upper gastrointestinal cancers having overall worse scores. The physical, social and psychological well-being of a majority of patients with dyspepsia in South-South Nigeria is negatively affected by dyspepsia.


Dyspepsia , Endoscopy, Gastrointestinal , Hospitals, Teaching , Quality of Life , Humans , Cross-Sectional Studies , Nigeria , Middle Aged , Female , Male , Adult , Aged , Young Adult , Activities of Daily Living , Gastrointestinal Neoplasms
20.
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
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