Interaction of Vitamin D Supplements and Marine n-3 Fatty Acids on Digestive Tract Cancer Prognosis.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

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

Gastrointestinal cancer (GIC) is the most prevalent and highly metastatic malignant tumor and has a significant impact on mortality rates. Nevertheless, the swift advancement of contemporary technology has not seamlessly aligned with the evolution of detection methodologies, resulting in a deficit of innovative and efficient clinical assays for GIC. Given that exosomes are preferentially released by a myriad of cellular entities, predominantly originating from neoplastic cells, this confers exosomes with a composition enriched in cancer-specific constituents. Furthermore, exosomes exhibit ubiquitous presence across diverse biological fluids, endowing them with the inherent advantages of non-invasiveness, real-time monitoring, and tumor specificity. The unparalleled advantages inherent in exosomes render them as an ideal liquid biopsy biomarker for early diagnosis, prognosticating the potential development of GIC metastasis.In this review, we summarized the latest research progress and possible potential targets on cancer-derived exosomes (CDEs) in GIC with an emphasis on the mechanisms of exosome promoting cancer metastasis, highlighting the potential roles of CDEs as the biomarker and treatment in metastatic GIC.

SALL4 in gastrointestinal tract cancers: upstream and downstream regulatory mechanisms.

Effective therapeutic targets and early diagnosis are major challenges in the treatment of gastrointestinal tract (GIT) cancers. SALL4 is a well-known transcription factor that is involved in organogenesis during embryonic development. Previous studies have revealed that SALL4 regulates cell proliferation, survival, and migration and maintains stem cell function in mature cells. Additionally, SALL4 overexpression is associated with tumorigenesis. Despite its characterization as a biomarker in various cancers, the role of SALL4 in GIT cancers and the underlying mechanisms are unclear. We describe the functions of SALL4 in GIT cancers and discuss its upstream/downstream genes and pathways associated with each cancer. We also consider the possibility of targeting these genes or pathways as potential therapeutic options for GIT cancers.

Financial difficulties experienced by patients with gastrointestinal stromal tumours (GIST) in the Netherlands: data from a cross-sectional multicentre study.

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

Endoscopic submucosal dissection for the treatment of a large inflammatory fibroid polyp in the gastric antrum prolapsing into the duodenum: A case report.

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

Surufatinib combined with transarterial embolization versus surufatinib monotherapy in patients with liver metastatic neuroendocrine tumors: Study protocol for a prospective, randomized, controlled trial.

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.

Application of the convolution neural network in determining the depth of invasion of gastrointestinal cancer: a systematic review and meta-analysis.

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

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

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

[Palliative Care in patients with gastrointestinal cancer]. / Palliativmedizin in der gastrointestinalen Onkologie.

Comprehensive Cancer Care stands for a concept of broad care providing substantial benefits to cancer patients. Beside prevention of cancer as first pillar and curative therapy as second pillar, comprehensive care also encompasses palliative care representing a third pillar providing service for incurable cancer patients burdened with physical symptoms and psychological, social and spiritual needs. This article describes the integration of palliative medicine into comprehensive cancer care for patients with gastrointestinal cancer.

[Immunotherapy for gastrointestinal cancer]. / Immuntherapie bei gastrointestinalen Tumoren.

Cancers of gastrointestinal tract make up the largest group of solid tumour diseases in Germany. The prognosis at diagnosis is often critical. Drug therapies reduce the risk of relapse after resection and can halt the progression of metastatic disease. Immunotherapies contribute increasingly to the treatment of gastrointestinal tumours. Monoclonal antibodies (mAB) against surface receptors from the epidermal growth factor receptor family (EGFR, Her2) are well established. The effect is partly based on the interruption of the oncogenic downstream signalling cascades and partly on immune effector mechanisms such as antibody-dependent cellular cytotoxicity. In clinical practice mAB directed against programmed cell death protein 1 (PD-1), its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) - so-called immune checkpoint inhibitors - play an increasing role and change the natural history of some subgroups of gastrointestinal cancers, especially those with deficient DNA mismatch repair which leads to genomic microsatellite instability.

A population-based cohort study of longitudinal change of high-density lipoprotein cholesterol impact on gastrointestinal cancer risk.

High-density Lipoprotein Cholesterol (HDL-C) levels have been associated with cancer. In this observational population-based cohort study using data from the Korean National Health Insurance Service system, we investigate the impact of longitudinal changes in HDL-C levels on gastrointestinal cancer risk. Individuals who underwent health examinations in 2010 and 2014 were followed-up through 2021. Among 3.131 million, 40696 gastric, 35707 colorectal, 21309 liver, 11532 pancreatic, 4225 gallbladder, and 7051 biliary cancers are newly detected. The persistent low HDL-C group increases the risk of gastric, liver, and biliary cancer comparing to persistent normal HDL-C group. HDL-C change from normal to low level increases the risk for gastric, colorectal, liver, pancreatic, gallbladder, and biliary cancers. Effects of HDL-C change on the gastrointestinal cancer risk are also modified by sex and smoking status. HDL-C changes affect the gastric and gallbladder cancer risk in age ≥60 years and the pancreatic and biliary cancer risk in age <60 years. Here, we show persistently low HDL-C and normal-to-low HDL-C change increase gastrointestinal cancer risk with discrepancies by sex, smoking status, and age.

The safety and efficacy of Compound Kushen Injection with chemoradiotherapy for the outcomes of lung and gastrointestinal cancers: A PRIMSA-compliant meta-analysis.

BACKGROUND: Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Radix Sophorae and Smilax glabra Roxb. CKI, as an antitumor preparation, plays a vital role in the clinical treatment of lung and gastrointestinal cancers. METHODS: Electronic databases such as the China National Knowledge Infrastructure, Wanfang data, PubMed, EMBASE, and Web of Science were searched for studies. The included studies were evaluated according to the Cochrane Handbook for Systematic Reviews, and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-four randomized controlled trials were selected for meta-analysis. The outcomes showed that CKI adjuvant therapy significantly improved complete remission (CR) and partial response (PR) compared to patients without CKI treatment in gastrointestinal cancers (CR: odds ratio [OR] = 1.76, 95% confidence interval [CI]: [1.29, 2.41], P = .0004; PR: OR = 1.64, 95% CI: [1.29, 2.07], P =.0001), and lung cancer (CR: OR = 2.18, 95% CI: [1.36, 3.51], P = .001); PR: OR = 1.81, 95% CI: [1.31, 2.50], P = .0003). CKI adjuvant therapy had a statistically significant advantage in optimizing life and health status (quality of life [QOL] for gastrointestinal cancers: MD = 1.76, 95% CI: [6.41, 13.80], P = .001, and Karnofsky performance status [KPS] for gastrointestinal cancers: MD = 4.64, 95% CI: [2.72, 6.57], P = .001; KPS for lung cancer: MD = 6.24, 95% CI [1.78, 10.71], P = .006). CKI reduced the pain in lung cancer patients (MD = -1.76, 95% CI: [-1.94, -1.58], P < .00001), increased immunity level (MD = 2.51, 95% CI: [2.17, 2.85], P < .00001), and alleviated the adverse reactions for lung and gastrointestinal cancers (MD = 0.38, 95% CI: (0.32, 0.46); P < .00001). CONCLUSION: The combination of CKI and chemoradiotherapy for treating lung and gastrointestinal cancer has positive effects on short-term and long-term outcomes and has advantages over chemoradiotherapy alone regarding safety and efficacy.

Cold EMR vs. Hot EMR for the removal of sessile serrated polyps larger than 10 mm: a systematic review and meta-analysis.

BACKGROUND: Endoscopic mucosal resection (EMR) appears to be a promising technique for the removal of sessile serrated polyps (SSPs) ≥ 10 mm. To assess the effectiveness and safety of EMR for removing SSPs ≥ 10 mm, we conducted this systematic review and meta-analysis. METHODS: We conducted a thorough search of Embase, PubMed, Cochrane, and Web of Science databases for relevant studies reporting on EMR of SSPs ≥ 10 mm, up until December 2023. Our primary endpoints of interest were rates of technical success, residual SSPs, and adverse events (AE). RESULTS: Our search identified 426 articles, of which 14 studies with 2262 SSPs were included for analysis. The rates of technical success, AEs, and residual SSPs were 100%, 2.0%, and 3.1%, respectively. Subgroup analysis showed that the technical success rates were the same for polyps 10-19 and 20 mm, and en-bloc and piecemeal resection. Residual SSPs rates were similar in en-bloc and piecemeal resection, but much lower in cold EMR (1.0% vs. 4.2%, P = 0.034). AEs rates were reduced in cold EMR compared to hot EMR (0% vs. 2.9%, P = 0.168), in polyps 10-19 mm compared to 20 mm (0% vs. 4.1%, P = 0.255), and in piecemeal resection compared to en-bloc (0% vs. 0.7%, P = 0.169). CONCLUSIONS: EMR is an effective and safe technique for removing SSPs ≥ 10 mm. The therapeutic effect of cold EMR is superior to that of hot EMR, with a lower incidence of adverse effects. PROSPERO REGISTRATION NUMBER: CRD42023388959.

Investigating the mortality trend of gastrointestinal cancers in Babol, North Iran (2013-2021).

BACKGROUND AND AIM: This study aims to examine the mortality rate and trend of gastrointestinal cancers, particularly gastric cancer, as the leading cause of death among cancers in northern Iran over a 9-year period. In light of the changing incidence and mortality rates of cancer in Iran and around the world, the importance of these diseases in people's lives, and the necessity of updating and monitoring the trend of cancer mortality, we have decided to report on the mortality trend of gastrointestinal cancers, based on crude and age-standardized rates. METHOD: This study is a cross-sectional examination of deaths caused by gastrointestinal cancers in Babol city, Iran, between 2013 and 2021. Data was collected from the cause of death registration and classification system of Babol University of Medical Sciences. Population estimation was obtained from the latest census reports. The crude and age-standardized mortality rates and trends of the cancers were calculated. RESULTS: Overall, there were 1345 deaths from gastrointestinal cancers with an average age of 69.11 ± 14.25 years. The crude and age-standardized rates of these cancers rose from 24.1 to 20.1 per hundred thousand people in 2012 to 29.5 and 25.5 per hundred thousand people, respectively. This trend became more prevalent significantly with the increase of each decade of age for both men (P-value Trend = 0.002) and women (P-value Trend = 0.012). An analysis of gastrointestinal cancers revealed a decreasing trend for cancers of the small intestine, an increasing trend for cancers of the colon, pancreas, and gallbladder, and a stable trend for the remaining cancers over the study period. CONCLUSION: The age-standardized rate and the number of gastrointestinal cancers is rising, highlighting the importance of preventative measures such as screening, increasing public awareness, and appropriate diagnostic methods.

A multicenter phase Ia study of AbGn-107, a novel antibody-drug conjugate, in patients with advanced gastrointestinal cancer.

AbGn-107 is an antibody-drug conjugate directed against AG-7 antigen, a Lewis A-like glycol-epitope expressed in a variety of gastrointestinal (GI) malignancies. Based on promising antitumor activity of AbGn-107 in both in vitro and in vivo preclinical studies, we performed a GI cancer-specific Phase I trial. Standard 3 + 3 dose escalation was used evaluating intravenous doses ranging from 0.1 mg/kg every 4 weeks to 1.0 mg/kg every 2 weeks. Key eligibility included chemo-refractory locally advanced, recurrent, or metastatic gastric, colorectal, pancreatic, or biliary cancer, with ECOG PS 0-1; positive AG-7 expression was not required during dose escalation phase. Patients were treated until disease progression or unacceptable toxicity, with tumor assessments every 8 weeks. Primary objectives included safety and determination of maximum tolerated dose; secondary objectives included efficacy defined by objective response rate. Thirty-nine patients were enrolled across seven dose levels during dose escalation phase. Based on safety profile and pharmacokinetic data, 1.0 mg/kg Q2W was selected as the dose schedule for cohort expansion phase, in which an additional seven patients were enrolled. Median number of lines of prior therapy was 3 (range 1-7). AbGn-107 was generally well-tolerated, with infections, cytopenias, hyponatremia, fatigue, abdominal pain, and diarrhea representing the most common grade 3 or higher treatment-emergent adverse events. One subject achieved a partial response, while 18 (46.2%) achieved a best response of stable disease. Disease control lasting > 6 months was observed in 6 subjects (13.0%), including 4 of 15 (26.7%) treated at the highest dose level. AbGn-107 showed a reasonable safety profile and modest clinical activity in this highly pretreated patient population. Further evaluation is required to assess the clinical validity of AG-7 as a suitable antigen for therapeutic targeting. Clinical Trial information: NCT02908451.

Impact of Perioperative Immunonutrition on Postoperative Outcomes in Patients with Upper Gastrointestinal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is no consensus on the efficacy of perioperative immunonutrition in patients with upper gastrointestinal (GI) cancer surgery. We clarified the impact of perioperative immunonutrition on postoperative outcomes in patients with upper GI cancers. We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981-2022 using search terms related to immunonutrition and upper GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy, including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. After screening, 23 studies were included in the qualitative synthesis and in the quantitative synthesis. The meta-analysis showed that immunonutrition reduced infectious complications (relative risk ratio: 0.72; 95% confidence interval: 0.57-0.92; certainty of evidence: Moderate) compared with standard nutritional therapy. In conclusion, nutritional intervention with perioperative immunonutrition in patients with upper GI cancers significantly reduced infectious complications. The effect of immunonutrition for upper GI cancers in reducing the risk of infectious complications was about 30%.

Low Adherence to Mediterranean Diet Characterizes Metabolic Patients with Gastrointestinal Cancer.

Background. Gastrointestinal (GI) cancers are one of the most relevant causes of death globally, frequently associated with poor dietary patterns. The Mediterranean Diet (MedDiet) contributes to cancer prevention. To assess adherence to MedDiet, our research group validated a new score, the Chrono Med Diet Score (CMDS), that captures increased visceral adiposity. Methods. We enrolled 401 subjects who underwent an evaluation for metabolic diseases and specific screening procedures according to current guidelines and were asked to answer CMDS. A total of 71 new cancer cases were recorded, including 40 GI and 31 non-gastrointestinal (NON-GI) cancers. Results. We found that CMDS was reduced in subjects who were diagnosed with cancers. Patients who reported a CMDS score of 12 or less had an over three times increased risk of being diagnosed with GI cancers and presented increased waist circumference and triglycerides and reduced HDL cholesterol compared to adherent subjects. Conclusions. Low CMDS values capture the risk for cancer diagnosis, especially for GI cancers. Thus, CMDS, along with waist circumference, can be considered as a bona fide marker for increased risk of cancer, requiring anticipated screening procedures for the detection of premalignant and early stage GI cancers in patients with low adherence to MedDiet.