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We propose a novel framework that addresses the deficiencies of Randomized clinical trial data subgroup analysis while it transforms ObservAtional Data to be used as if they were randomized, thus paving the road for precision medicine. Our approach counters the effects of unobserved confounding in observational data through a two-step process that adjusts predicted outcomes under treatment. These adjusted predictions train decision trees, optimizing treatment assignments for patient subgroups based on their characteristics, enabling intuitive treatment recommendations. Implementing this framework on gastrointestinal stromal tumors (GIST) data, including genetic sub-cohorts, showed that our tree recommendations outperformed current guidelines in an external cohort. Furthermore, we extended the application of this framework to RCT data from patients with extremity sarcomas. Despite initial trial indications of universal treatment necessity, our framework identified a subset of patients who may not require treatment. Once again, we successfully validated our recommendations in an external cohort. [ABSTRACT FROM AUTHOR]

Intratumoral microbiota and host genes interact to promote gastrointestinal disorders, but how the two interact to influence host tumorigenesis remains unclear. Here, we utilized a machine learning-based framework to jointly dissect the paired intratumoral microbiome and host transcriptome profiles in patients with colon adenocarcinoma, hepatocellular carcinoma, and gastric cancer. We identified associations between intratumoral microbes and host genes that depict shared as well as cancer type-specific patterns. We found that a common set of host genes and pathways implicated in cell proliferation and energy metabolism are associated with cancer type-specific intratumoral microbes. In addition, we also found that intratumoral microbes that have been implicated in three gastrointestinal tumors, such as Lachnoclostridium, are correlated with different host pathways in each tumor, indicating that similar microbes can influence host tumorigenesis in a cancer type-specific manner by regulation of different host genes. Our study reveals patterns of association between intratumoral microbiota and host genes in gastrointestinal tumors, providing new insights into the biology of gastrointestinal tumors. NEW & NOTEWORTHY: Our study constitutes a pivotal advancement in elucidating the intricate relationship between the intratumoral microbiome and host gene regulation, thereby gaining insights into the pivotal role that the intratumoral microbiome plays in the etiology of gastrointestinal tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: This study involved 2745 participants from a southern Italian cohort. The objective was to investigate the link between the consumption of extra virgin olive oil and the risk of mortality from all causes and, in particular, from gastrointestinal cancers and other cancers. The study found that individuals who consumed more than 50 g of extra virgin olive oil per day had a 60 percent lower risk of death from gastrointestinal cancers than those who consumed less than 30 g per day. Furthermore, daily consumption of 50 g of extra virgin olive oil was associated with a 50 percent lower risk of death from other cancers compared to the lowest consumption category. This study concluded that higher olive oil consumption in this cohort of Italian Mediterranean adults was linked to a reduced risk of cancer and all-cause mortality, probably due to the health benefits of the Mediterranean diet. Background/Objectives: This study investigates the association between extra virgin olive oil (EVOO) consumption and mortality risk in a cohort of Italian adults adhering to the Mediterranean diet. Methods: In a 17-year follow-up study involving participants from Castellana Grotte, Italy (2005–2023), we analyzed dietary intake and mortality data. Participants were categorized into three EVOO consumption groups: <30 g/day, 30–50 g/day, and >50 g/day. Mortality Hazard Ratios (HR) and Subdistribution Hazard Ratios (SHR) were calculated to assess the relationship between EVOO intake and all-cause and cancer mortality. Results: Higher EVOO consumption was associated with significantly reduced cancer and all-cause mortality. Specifically, the daily intake of 30–50 g of EVOO was linked to a 24% lower risk of all-cause mortality (HR 0.77; 95% CI 0.63–0.93), while the consumption of more than 50 g/day was associated with a 20% reduction (HR 0.80; 95% CI 0.65–0.98). The most pronounced benefit was observed for gastrointestinal cancers, with a 60% lower mortality risk for those consuming over 50 g/day (SHR 0.39; 95% CI 0.21–0.73). A 50% reduction in mortality risk from other cancers was also noted for the highest consumption category (SHR 0.50; 95% CI 0.31–0.81). Conclusions: The findings support the beneficial role of EVOO in reducing cancer mortality, particularly with higher consumption levels. The results underscore EVOO's potential as a dietary intervention for cancer prevention, aligning with the Mediterranean diet's overall health benefits. Further research is needed to confirm these findings and explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated comparable outcomes between laparoscopic and open resection of gastrointestinal stromal tumor (GIST). We sought to compare outcomes among robotic, laparoscopic, and open resection of gastric GIST in the era of expanding minimally invasive surgery. Methods: A retrospective analysis was performed of adult patients with gastric GIST undergoing definitive surgery using the National Cancer Database from 2010 to 2020, excluding cases converted to open. Patients were stratified into minimally invasive surgery (MIS), (combined robotic (R) and laparoscopic (L)), and open (O). Hospital length of stay (LOS), 30-day mortality, 90-day mortality, and margin status were assessed. Subgroup analysis was performed to evaluate outcomes between R and L cohorts. Entropy balancing was used to adjust for intergroup differences. Kaplan–Meier survival estimates were used to compare unadjusted 5-year survival. Results: Of the 15,022 patients (R = 10.4%, L = 44.3%, O = 45.3%), 63.2% were stage I and 70.6% underwent partial gastrectomy. MIS approach was associated with shorter hospital LOS (β: − 2.58; 95% CI: − 2.82 to − 2.33) and lower odds of 30-day (OR 0.45; 95% CI: 0.30–0.68) and 90-day mortality (OR 0.54; 95% CI: 0.39–0.74) compared to O. Likelihood of R0 resection similar between groups (OR 1.00; 95% CI: 0.88–1.14). Hospital LOS (β: + 0.25; 95% CI: − 0.14–0.64), odds of 30-day (OR 0.99; 95% CI: 0.40–2.46) and 90-day mortality (OR 0.89; 95% CI: 0.47–1.70), and rate of R0 resection (OR 1.02; 95% CI: 0.82–1.27) were comparable between R and L cohorts. Compared to O, MIS approach was associated with improved 5-year OS (log rank p < 0.001). Overall survival was not significantly different between R and L (log rank p = 0.44). Conclusion: These findings suggest that MIS approach may be considered for resection of gastric GIST in select patients. Among patients receiving an MIS approach, the robotic technique can be considered an oncologically safe alternative to laparoscopic surgery. [ABSTRACT FROM AUTHOR]

Recent advances in tumor immunology and molecular drug development have ushered in a new era of cancer immunotherapy. Immunotherapy has shown promising results for several types of tumors, such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin's lymphoma. Similarly, efforts have been made to develop immunotherapies such as adoptive T-cell transplantation, peptide vaccines, and dendritic cell vaccines, specifically for gastrointestinal tumors. However, before the advent of immune checkpoint inhibitors, immunotherapy did not work as well as expected. In this article, we review immunotherapy, focusing on cancer vaccines for gastrointestinal tumors, which generally target eliciting tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). We also review various vaccine therapies and describe the relationship between vaccines and adjuvants. Finally, we discuss prospects for the combination of immunotherapy with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Background: Pimitespib (TAS‐116), a first‐in‐class, oral, selective heat‐shock protein 90 inhibitor, is approved as fourth‐line treatment for gastrointestinal stromal tumors in Japan. This phase 1 study evaluated the cardiac safety of pimitespib. Methods: In this open‐label, nonrandomized, multicenter study, Japanese patients (aged ≥20 years) with refractory, advanced solid tumors received placebo on day −1, then pimitespib 160 mg daily on days 1–5 of the cardiac safety evaluation period. Electrocardiograms were conducted at baseline, and on days −2, −1, 1, and 5; and blood samples were collected on days 1 and 5. Patients then received once‐daily pimitespib for 5 days every 3 weeks. The primary end point was the time‐matched difference in QT interval corrected for heart rate using the Fridericia correction (QTcF) between pimitespib and placebo. Pharmacokinetics, safety, and preliminary efficacy were also assessed. Results: Of the 22 patients in the cardiac safety‐evaluable population, no clinically relevant QTc prolongation was observed; the upper bound of the one‐sided 95% confidence interval for the time‐matched difference in change from baseline in QTcF was <20 msec at all time points on days 1 and 5. Pimitespib pharmacokinetic parameters were consistent with previous data, and the time‐matched difference in change from baseline in QTcF showed no marked increase as plasma concentrations increased. The safety profile was acceptable; 40% of patients experienced grade 3 or greater adverse drug reactions, mostly diarrhea (20%). The median progression‐free survival was 3.1 months. Conclusions: In Japanese patients with refractory, advanced solid tumors, pimitespib was not associated with clinically relevant QTc prolongation, and there were no cardiovascular safety concerns. Plain Language Summary: Pimitespib is a new anticancer drug that is being used to treat cancer in the stomach or intestines (gastrointestinal stromal tumors).This study demonstrated that pimitespib had no marked effect on heart rhythm or negative effects on the heart or blood vessels and had promising anticancer effects in Japanese patients with advanced solid tumors who were unable to tolerate or benefit from standard treatment. [ABSTRACT FROM AUTHOR]

Due to the major improvements in the hardware and image reconstruction algorithms, positron emission tomography/magnetic resonance imaging (PET/MR) is now a reliable state-of-the-art hybrid modality in medical practice. Currently, it can provide a broad range of advantages in preclinical and clinical imaging compared to single-modality imaging. In the second part of this review, we discussed the further clinical applications of PET/MR. In the chest, PET/MR has particular potential in the oncology setting, especially when utilizing ultrashort/zero echo time MR sequences. Furthermore, cardiac PET/MR can provide reliable information in evaluating myocardial inflammation, cardiac amyloidosis, myocardial perfusion, myocardial viability, atherosclerotic plaque, and cardiac masses. In gastrointestinal and hepato-pancreato-biliary malignancies, PET/MR is able to precisely detect metastases to the liver, being superior over the other imaging modalities. In genitourinary and gynaecology applications, PET/MR is a comprehensive diagnostic method, especially in prostate, endometrial, and cervical cancers. Its simultaneous acquisition has been shown to outperform other imaging techniques for the detection of pelvic nodal metastases and is also a reliable modality in radiation planning. Lastly, in haematologic malignancies, PET/MR can significantly enhance lymphoma diagnosis, particularly in detecting extra-nodal involvement. It can also comprehensively assess treatment-induced changes. Furthermore, PET/MR may soon become a routine in multiple myeloma management, being a one-stop shop for evaluating bone, bone marrow, and soft tissues. [ABSTRACT FROM AUTHOR]

Over the next few years, the analysis of circulating tumor DNA (ctDNA) through liquid biopsy is expected to enter clinical practice and revolutionize the approach to biomarker testing and treatment selection in GI cancers. In fact, growing evidence support the use of ctDNA testing as a noninvasive, effective, and highly specific tool for molecular profiling in GI cancers. Analysis of blood ctDNA has been investigated in multiple settings including early tumor detection, minimal residual disease evaluation, tumor diagnosis and evaluation of prognostic/predictive biomarkers for targeted treatment selection, longitudinal monitoring of treatment response, and identification of resistance mechanisms. Here, we review the clinical applications, advantages, and limitations of ctDNA profiling for precision oncology in GI cancers. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a prevalent malignant tumor of the gastrointestinal system, with the third and second highest incidence and mortality rates globally in 2020, respectively. Immunotherapy has developed rapidly in recent years. Natural killer (NK) cells have received increasing attention in the field of tumor immunotherapy due to their recognition and killing tumor cells without the limitations of major histocompatibility complexes. However, constraints within the tumor microenvironment that impede the infiltration and proliferation of NK cells result in poor efficacy of NK cell therapy for solid tumors. Oncolytic viral therapy is an immunogenic treatment with the potential to enhance anti-tumour immune responses and promote immune cell infiltration. In this study, we synergistically combine NK cells with an oncolytic adenovirus carrying Decorin (rAd.DCN) for the treatment of colorectal cancer (CRC) in a xenograft mouse model. By using Flow cytometry, real-time quantitative PCR and Calcein-AM release assay, we found that rAd.DCN could effectively promote proliferation, activation and degranulation of NK cells, up-regulate expression and secretion of NK cell killing activity-related factors, and enhance their killing activity. The efficacy is better than that of the blank control oncolytic virus rAd.Null. Combined treatment significantly inhibited tumor growth, increased the number of NK cells in peripheral blood, promoted the killing function of NK cells, and increased the expression levels of perforin and IFN-γ. At the same time, more NK cells were recruited to infiltrate tumor tissue. Our study established the feasibility of combination NK cells and oncolytic adenovirus application, thus expanding the scope of potentially curative treatments for NK cells in CRC. [ABSTRACT FROM AUTHOR]

Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer is a common malignant tumor with a high incidence worldwide. Despite continuous improvements in diagnosis and treatment strategies, the overall prognosis of gastrointestinal tumors remains poor. Carcinoembryonic antigen (CEA) is highly expressed in various types of cancers, especially in gastrointestinal cancers, making it a potential target for therapeutic intervention. Therefore, the expression of CEA can be used as an indication of the existence of tumors, chosen as a target for molecular imaging diagnosis, and effectively utilized in the targeted therapy of gastrointestinal cancers. In this study, we report the selection and characterization of affibody molecules (ZCEA539, ZCEA546, and ZCEA919) specific to the CEA protein. Their ability to bind to recombinant and native CEA protein has been confirmed by surface plasmon resonance (SPR), immunofluorescence, and immunohistochemistry assays. Furthermore, Dylight755-labeled ZCEA affibody showed accumulation within the tumor site 1 h post injection and was continuously enhanced for 4 h. The Dylight755-labeled ZCEA affibody exhibited high tumortargeting specificity in CEA+ xenograft-bearing mice and possesses promising characteristics for tumor-targeting imaging. Overall, our results suggest the potential use of ZCEA affibodies as fluorescent molecular imaging probes for detecting CEA expression in gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Many patients diagnosed with gastroenteropancreatic neuroendocrine tumors present with metastatic disease at the time of diagnosis. As many as 20% of patients with this diagnosis will present with metastasis to the peritoneal cavity which portends a significantly worse prognosis than solid organ metastasis alone. There is little to no evidence to guide treatment algorithms given the rarity of this disease. Surgical cytoreduction has been found to improve symptoms related to disease burden, though an understanding of the optimal cytoreductive strategies to offer the greatest benefit to most patients is lacking. While the current body of literature pertaining to the systemic treatment of the solid organ metastasis of this disease is more robust, it largely excludes patients with peritoneal metastasis. We provide a review of the current literature which is used to guide these management strategies and offer insight into the knowledge gaps that exist. Peritoneal metastasis in gastroenteropancreatic neuroendocrine tumors poses a significant clinical challenge, with limited data guiding management strategies. We review the existing literature on surgical and systemic treatment modalities for peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors. Surgical interventions, including cytoreductive surgery, have shown promise in improving symptom control and overall survival—particularly in cases in which 70% cytoreduction can be achieved. Hyperthermic intraperitoneal chemotherapy remains controversial due to a paucity of high-level evidence and a lack of consensus for routine use. The use of systemic therapy in the setting of peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors is extrapolated from high-quality evidence for its use in the setting of the solid organ metastasis of this disease. The use of somatostatin analogs for symptom control and some antiproliferative effects is supported by large clinical trials. Additional strong evidence exists for the use of interferon-alpha, everolimus, and sunitinib, particularly in pancreatic neuroendocrine tumors. Cytotoxic chemotherapy and peptide receptor radionuclide therapy may be used in select cases, though as an emerging treatment modality, the optimal sequence of peptide receptor radionuclide therapy within the existing algorithms is unknown. Significant gaps in understanding and standardized management exist, particularly for those patients presenting with peritoneal metastasis, and targeted research to optimize outcomes in this population is needed. [ABSTRACT FROM AUTHOR]

Background: The purpose of this research was to evaluate the efficacy of Narcotrend (NT) monitoring on cognitive dysfunction in patients undergoing anesthesia blockade for gastrointestinal tumors and its effect on cerebral oxygen metabolism and inflammatory response. Methods: Patients preparing to undergo resection of gastrointestinal tumor resection were included and randomly divided into a control group (depth of anesthesia assessed by physician experience) and a research group (depth of anesthesia monitored by NT). HR and MAP were monitored at the preoperatively (T0), 12 h postoperative (T1), 24 h postoperative (T2), and 48 h postoperative (T3) stages. MMSE score was recorded to assess changes in cognitive function. Intracerebral oxygenation indicators (CjvO2, CERO2, and rSO2) were assessed by a blood gas analyzer. ELISA assay was conducted to explore the serum inflammatory indexes (CRP, IL-1β, and TNF-α) and neurological function indicators (NSE and MBP). Results: MAP was higher in the research group than in the control group at T1 and T2 (P < 0.05). MMSE scores at T1, T2, and T3 stages were higher in the research group than in the control (P < 0.05). The incidence of POCD was also lower in the research group compared with the control (P < 0.05). CjvO2, CERO2, and rSO2 were significantly higher (P < 0.05) and were positively correlated with the MMSE scores. Postoperative serum inflammatory indexes were significantly elevated in both groups, but more significantly in the control group (P < 0.05). Both neurological function indicators were usually reduced after surgery, but the reduction was more significant in the research group (P < 0.05). Conclusion: NT monitoring of anesthetic depth has a less physical impact on patients with gastrointestinal tumor anesthetic block, reduces the degree of postoperative POCD, and has significant clinical value. [ABSTRACT FROM AUTHOR]

The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy. [ABSTRACT FROM AUTHOR]

Objective: Oxaliplatin is a platinum-group chemotherapeutic agent commonly used in the treatment of colorectal cancer. In addition to hematological and gastrointestinal side effects, laryngopharyngeal dysesthesia associated with cold is reported as a rare side effect. In this article, seven cases with pharyngolaryngeal dysesthesia were presented and the diagnosis and treatment planning were reviewed in the light of literature findings. Material and Methods: Patient records of cancer patients with laryngopharyngeal dysesthesia were retrospectively analyzed between 2020 and 2023. Demographic characteristics, presenting complaints, vital signs, physical examination, and laboratory tests of the patients diagnosed with laryngopharyngeal dysesthesia were recorded. Results: Seven patients who had gastrointestinal malignancy and oxaliplatin chemotherapy were diagnosed with laryngopharyngeal dysesthesia. The symptoms most commonly developed due to cold weather. The symptoms of three patients had developed while receiving treatment, while four patients were admitted to emergency service after oxaliplatin infusion. The physical examinations revealed no pathological findings of the allergic reaction at presentation or during follow-up skin. Patients were monitored and nasal oxygen therapy was administered. A 5 mg intravenous infusion was given for anxiety symptoms in three patients. Patients were discharged after 4 hours of follow-up with resolution of all symptoms Conclusion: Laryngopharyngeal dysesthesia should be kept in mind in patients treated with oxaliplatin and presenting with shortness of breath and a feeling of suffocation after cold exposure. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer affects millions worldwide, with gastrointestinal cancers being notably common. This review explores the potential of telomeres and telomerase as biomarkers for diagnosing and predicting these cancers. Telomeres are protective caps at chromosome ends that shorten with cell division, while telomerase helps extend them. Changes in these markers could indicate cancer risk and progression. Despite efforts to prevent cancer through lifestyle changes, gastrointestinal cancers such as colorectal and gastric cancer remain prevalent. Current detection methods like endoscopy are invasive, driving interest in non-invasive alternatives. By consolidating research on telomere length and telomerase activity, this review aims to highlight how these biomarkers could enhance early diagnosis and monitoring. Understanding these mechanisms better could lead to improved diagnostic tools and therapeutic strategies, potentially refining how gastrointestinal cancers are managed and improving patient outcomes. Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers. [ABSTRACT FROM AUTHOR]

Simple Summary: Neuroendocrine neoplasms, primarily found in the gastroenteropancreatic tract, are classified as neuroendocrine tumours and neuroendocrine carcinomas, depending on the grade. Liquid biopsy offers a less invasive alternative to tissue biopsy in detecting circulating tumour components in body fluids. This systematic review evaluates liquid biopsy applications in neuroendocrine neoplasms, approaching its various types in different settings, such as diagnosis and characterisation; prognostic and predictive value; monitoring treatment response and prediction of recurrence; and finally, current applications and future perspectives. Overall, liquid biopsy holds potential for managing neuroendocrine neoplasms, and its use should be standardised. Neuroendocrine neoplasms incidence has been increasing, arising the need for precise and early diagnostic tools. Liquid biopsy (LB) offers a less invasive alternative to tissue biopsy, providing real-time molecular information from circulating tumour components in body fluids. The aim of this review is to analyse the current evidence concerning LB in NENs and its role in clinical practice. We conducted a systematic review in July 2024 focusing on LB applications in NENs, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), micro RNA (miRNA), messenger RNA (mRNA) and extracellular vesicles. Sixty-five relevant articles were analysed. The LB showed potential in diagnosing and monitoring NENs. While CTCs face limitations due to low shedding, ctDNA provides valuable information on high-grade neoplasms. MiRNA and mRNA (e.g., the NETest) offer high sensitivity and specificity for diagnosis and prognosis, outperforming traditional markers like chromogranin A. The LB has significant potential for NEN diagnosis and monitoring but lacks widespread clinical integration due to limited prospective studies and guidelines, requiring further validation. Advances in sequencing technologies may enhance the clinical utility of LB in NENs. Future research should focus on refining LB methods, standardising protocols and exploring applications in high-grade NENs. [ABSTRACT FROM AUTHOR]

This document provides information on the management of incidentally found gastrointestinal neuroendocrine tumors (NENs) and specifically focuses on gastric NENs and rectal NENs. Gastric NENs can be classified into three types and are typically managed with endoscopic resection and surveillance, while type 3 gastric NENs may require surgical resection. Rectal NENs should be removed due to their metastatic potential, and the recommended technique for resection is endoscopic mucosal resection with ligation (EMR-L). Correct identification of rectal NENs is crucial to ensure complete resection, and follow-up imaging or colonoscopy may be necessary. Multidisciplinary decision-making is important for larger lesions. This information is valuable for clinicians and researchers studying the management of gastrointestinal NENs. [Extracted from the article]

SMARCA4-deficient undifferentiated tumors (SMARCA4-UT) are a newly described entity and are typically seen in the thoracic cavity. However, these tumors have been described in other body sites, including the esophagus. These tumors are rare, aggressive neoplasms, characterized by the loss of protein product of SMARCA4 (Brahma-related gene-1) and the preservation of INI1 (SMARCB1) expression. Here, we present two tumors of SMARCA4-UT of the esophagus with its microscopic appearance and immunohistochemical profile. We also include a literature review of SMARCA4-deficient tumors of the tubular gastrointestinal tract with their immunohistochemical and mismatch repair profiles for each specimen. Due to its non-specific histologic appearance and variable staining in expanded immunohistochemical panels, this tumor frequently overlaps with other tumor types, making the diagnosis of SMARCA4-UT challenging. These tumors are often associated with intestinal metaplasia of the esophagus and are thought to represent a high-grade undifferentiated transformation of a conventional esophageal adenocarcinoma. These tumors are typically associated with poor clinical outcomes and have poor response to conventional therapies. Currently, there are no standard guidelines for treatment of these tumors; however, palliative radiotherapy and systemic chemotherapy may provide benefit. More recently, immunotherapy and novel therapeutic targets have shown some promise for these patients. [ABSTRACT FROM AUTHOR]

A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications. The patient had been diagnosed with B-cell chronic lymphocytic leukemia (CLL) years prior to the MTB presentation. GIST had been diagnosed 1 month earlier. After structured clinical annotation of the molecular alterations and interdisciplinary discussion, we considered BRAF/KIT co-mutation unlikely in a treatment-naïve GIST. Discordant variant allele frequencies furthermore suggested a second malignancy. NGS of a CLL sample revealed the identical class 2 BRAF alteration, thus supporting admixture of CLL cells in the paragastric mass, leading to the detection of 2 alterations. Following the MTB recommendation, the patient received imatinib and had a radiographic response. Structured annotation and interdisciplinary discussion in specialized tumor boards facilitate the clinical management of complex molecular findings. Coexisting malignancies and clonal hematopoiesis warrant consideration in case of complex and uncommon molecular findings. [ABSTRACT FROM AUTHOR]

Background Oxaliplatin- and fluoropyrimidine-based triplet regimens have demonstrated feasibility and efficacy in the treatment of upper gastrointestinal (UGI) cancers. Herein, we evaluate the feasibility and preliminary efficacy of biweekly nab-paclitaxel plus oxaliplatin and S-1/leucovorin (SOLAR) in chemonaïve UGI cancers. Methods A 3 + 3 phase 1 study was conducted to determine the maximal tolerated dose (MTD) of oxaliplatin in SOLAR (nab-paclitaxel [150 mg/m2 in D1], oxaliplatin [60, 75, or 85 mg/m2 in D1], and oral S-1/leucovorin [35 mg/m2 and 30 mg bid from D1 to D7]). The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results Thirteen and 6 accruals were in the dose-escalation and MTD expansion cohorts, respectively. One of 6 patients at level III experienced dose-limiting toxicity (grade 3 diarrhea), which revealed that the MTD of oxaliplatin was 85 mg/m2. After a mean of 15.9 cycles of treatment, the most common treatment-related grade 3/4 toxicities were neutropenia (57.9%) and diarrhea (21.1%). The ORR was 63.2%. The median PFS and OS were 12.5 and 24.7 months, respectively. Conclusion The current study revealed the MTD of oxaliplatin and demonstrated the preliminary efficacy of SOLAR in UGI cancers, which deserves further investigation. ClinicalTrials.gov Identifier NCT03162510 [ABSTRACT FROM AUTHOR]

Ferroptosis is a new form of cell death that differs from traditional forms of death. It is ferroptosis-dependent lipid peroxidation death. Colorectal cancer(CRC) is the most common tumor in the gastrointestinal tract with a long occultation period and a poor five-year prognosis. Exploring effective systemic treatments for CRC remains a great challenge worldwide. Numerous studies have demonstrated that ferroptosis can participate in the biological malignant process of various tumor, including CRC, so understanding the role and regulatory mechanisms of ferroptosis in CRC plays a crucial role in the treatment of CRC. In this paper, we reviews the mechanisms of ferroptosis in CRC, the associated regulatory factors and their interactions with various immune cells in the immune microenvironment. In addition, targeting ferroptosis has emerged as an encouraging strategy for CRC treatment. Finally, to inform subsequent research and clinical diagnosis and treatment, we review therapeutic approaches to CRC radiotherapy, immunotherapy, and herbal therapy targeting ferroptosis. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer. [ABSTRACT FROM AUTHOR]

Abstract Gastrointestinal tumors are the main causes of death among the patients. These tumors are mainly diagnosed in the advanced stages and their response to therapy is unfavorable. In spite of the development of conventional therapeutics including surgery, chemotherapy, radiotherapy and immunotherapy, the treatment of these tumors is still challenging. As a result, the new therapeutics based on (nano)biotechnology have been introduced. Hydrogels are polymeric 3D networks capable of absorbing water to swell with favorable biocompatibility. In spite of application of hydrogels in the treatment of different human diseases, their wide application in cancer therapy has been improved because of their potential in drug and gene delivery, boosting chemotherapy and immunotherapy as well as development of vaccines. The current review focuses on the role of hydrogels in the treatment of gastrointestinal tumors. Hydrogels provide delivery of drugs (both natural or synthetic compounds and their co-delivery) along with gene delivery. Along with delivery, hydrogels stimulate phototherapy (photothermal and photodynamic therapy) in the suppression of these tumors. Besides, the ability of hydrogels for the induction of immune-related cells such as dendritic cells can boost cancer immunotherapy. For more specific cancer therapy, the stimuli-responsive types of hydrogels including thermo- and pH-sensitive hydrogels along with their self-healing ability have improved the site specific drug delivery. Moreover, hydrogels are promising for diagnosis, circulating tumor cell isolation and detection of biomarkers in the gastrointestinal tumors, highlighting their importance in clinic. Hence, hydrogels are diagnostic and therapeutic tools for the gastrointestimal tumors.

Background: Among mesenchymal tumors arising in the gastrointestinal tract, gastrointestinal stromal tumors are the most common. GISTs that do not have metastatic spread are treated surgically. Our case report aims to describe a newer & less invasive approach for resection of GISTs & early gastrointestinal tumors. Case Presentation: An Iranian woman 41 years old with stomach stromal tumor is presented. Her complaint was minor epigastric discomfort. Tumor en-bloc resection was performed using a hybrid endoscopic-laparoscopic approach. She was doing very well & discharged the day after the operation. Conclusion: GISTs and early gastrointestinal tumors can be treated with hybrid endoscopic and laparoscopic en-bloc resections instead of invasive surgery. [ABSTRACT FROM AUTHOR]

Donglin Jiang,1 Yangxue Wu,1 Ling Liu,1 Yajing Shen,1 Tiandong Li,1 Yin Lu,1 Peng Wang,2 Changqing Sun,2 Kaijuan Wang,2 Keyan Wang,3 Hua Ye1 1College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China; 2Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China; 3Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of ChinaCorrespondence: Hua Ye, College of Public Health, Zhengzhou University, Gaoxin District, Zhengzhou, Henan, 450001, People’s Republic of China, Tel +86 186-3853-6001, Fax +86 371-67781018, Email yehua@zzu.edu.cnBackground: Gastrointestinal tumors represent a significant component of the cancer burden in Asia. This study aims to evaluate the burden of gastrointestinal tumors in Asia from 1990 to 2021 using data from the Global Burden of Disease Study 2021 (GBD 2021).Methods: The absolute incidence, mortality, and disability adjusted life years (DALYs) number and rate of six gastrointestinal tumors(colon and rectum cancer (CRC), stomach cancer (SC), pancreatic cancer (PC), esophageal cancer (EC), liver cancer (LC) and gallbladder and biliary tract cancer (GBTC)) in 48 Asian countries were extracted from GBD 2021. Differences were analyzed based on gender, age, year, location and socio-demographic index (SDI).Results: In 2021, SC accounted for the highest disease burden in Asia (DALYs=16.41million [95% UI: 13.70, 19.62]). From 1990 to 2021, the age-standardized incidence rates of EC, LC, and SC in Asia declined, while the incidence rates of CRC and PC increased significantly, with CRC showing the largest rise (AAPC=1.08 [95% CI: 1.02 to 1.12]). Gastrointestinal tumors DALY rates peaked at age 70 and above, with males generally exhibiting higher rates than females. Furthermore, East Asia bears a higher burden compared to other Asian subregions. A higher SDI correlates with increased DALY rates for PC, but no linear relationship was observed for other gastrointestinal tumors.Conclusion: The burden of gastrointestinal tumors in Asia remains high and may continue to increase. Therefore, effective prevention and treatment measures are essential to address the challenge posed by gastrointestinal tumors.Keywords: Asia, gastrointestinal tumors, burden, trends

Abstract Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, affecting millions each year. It emerges from the colon or rectum, parts of the digestive system, and is closely linked to both genetic and environmental factors. In CRC, genetic mutations such as APC, KRAS, and TP53, along with epigenetic changes like DNA methylation and histone modifications, play crucial roles in tumor development and treatment responses. This paper delves into the complex biological underpinnings of CRC, highlighting the pivotal roles of genetic alterations, cell death pathways, and the intricate network of signaling interactions that contribute to the disease's progression. It explores the dysregulation of apoptosis, autophagy, and other cell death mechanisms, underscoring the aberrant activation of these pathways in CRC. Additionally, the paper examines how mutations in key molecular pathways, including Wnt, EGFR/MAPK, and PI3K, fuel CRC development, and how these alterations can serve as both diagnostic and prognostic markers. The dual function of autophagy in CRC, acting as a tumor suppressor or promoter depending on the context, is also scrutinized. Through a comprehensive analysis of cellular and molecular events, this research aims to deepen our understanding of CRC and pave the way for more effective diagnostics, prognostics, and therapeutic strategies.

Background: Heart failure (HF) and colorectal cancer are significant public health concerns with substantial morbidity and mortality. Previous studies have indicated a close association between HF and various tumors, including colorectal cancer. Further understanding the potential causal relationship between them could provide insights into their shared pathophysiological mechanisms and inform strategies for prevention and treatment. Methods: This study employed a bidirectional Mendelian randomization (MR) approach using genetic variants from large genome-wide association studies (GWAS) as instrumental variables (IVs). The inverse-variance weighted (IVW) method was employed for the MR analysis. Meta-analyses of IVW results from discovery and validation cohortswere performed to enhance the power of detecting causal effects. Sensitivity analyses, including heterogeneity analysis and tests for horizontal pleiotropy, were conducted to test the robustness of the conclusions. Results: Results from the discovery cohort suggest HF is associated with an approximately 30% increased risk of colorectal cancer (OR 1.32, 95% CI 1.03-1.69, P=0.025), although this finding did not reach statistical significance in the validation cohort (OR 1.19, 95% CI 0.97-1.46, P=0.090). However, meta-analysis supports HF as a potential risk factor for colorectal cancer (Pooled OR 1.24, 95% CI 1.06-1.25, P=0.007). Reverse MR analysis found no evidence of colorectal cancer increasing HF risk (Pooled OR 1.03, 95% CI 0.99-1.07, P=0.121). Sensitivity analyses (all P>0.05) indicate robustness against heterogeneity and horizontal pleiotropy. Conclusion: This comprehensive bidirectional MR study provides genetic evidence supporting a causal link between HF and colorectal cancer. The insights gained enhance understanding of their interconnectedness and may guide future research and clinical practices aimed at mitigating their risks through targeted interventions. [ABSTRACT FROM AUTHOR]

Simple Summary: Stem cells are unique cell types in our body that play a key role in organ development and repair. Various inflammatory molecules act as critical regulators of stem cell activity. The dysregulation of inflammation and stem cell signaling pathways leads to a variety of diseases, including cancer. This review summarizes the role of inflammatory signals in regulating stem cell function within the gastrointestinal (GI) tract. We further discuss the studies highlighting the role of stem cells in the initiation and progression of cancers of the GI tract. We also report on various studies that assess the prognostic and therapeutic utility of cancer stem cells and their molecular markers in GI cancers. Stem cells are critical for the development and homeostasis of the gastrointestinal (GI) tract. Inflammatory molecules are known to regulate the activity of stem cells. A comprehensive review specifically describing the role of inflammatory molecules in the regulation of stem cells within the GI tract and in GI cancers (GICs) is not available. This review focuses on understanding the role of inflammatory molecules and stem cells in maintaining homeostasis of the GI tract. We further discuss how inflammatory conditions contribute to the transformation of stem cells into tumor-initiating cells. We also describe the molecular mechanisms of inflammation and stem cell-driven progression and metastasis of GICs. Furthermore, we report on studies describing the prognostic value of cancer stem cells and the clinical trials evaluating their therapeutic utility. This review provides a detailed overview on the role of inflammatory molecules and stem cells in maintaining GI tract homeostasis and their implications for GI-related malignancies [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion Endoscopic full‐thickness resection (EFTR) for submucosal tumors (SMTs) has been technically challenging. This retrospective study aimed to evaluate the feasibility, safety, and efficacy of EFTR for upper gastrointestinal (GI) SMTs, including extraluminal lesions.We retrospectively investigated 232 patients with SMTs who underwent EFTR from January 2014 to August 2023. Clinicopathologic characteristics, procedure‐related parameters, adverse events (AEs), and follow‐up outcomes were assessed in all patients.The en‐bloc resection and en‐bloc with R0 resection rates were 98.7% and 96.1%, respectively. The average endoscopic tumor size measured 17.2 ± 8.7 mm, ranging from 6 to 50 mm. The resection time and suture time were 49.0 ± 19.4 min and 22.5 ± 11.6 min, respectively. In all, 39 lesions (16.8%) exhibited predominantly extraluminal growth. Gastrointestinal stromal tumors (GISTs) were the predominant pathology, accounting for 78.4% of the cases. Twenty‐one patients (9.1%) encountered complications, including pneumothorax (1/232, 0.43%), hydrothorax (1/232, 0.43%), localized peritonitis (3/232, 1.29%), and fever (16/232, 6.9%). Although the incidence of postoperative fever was notably higher in the predominantly extraluminal group (7/39, 17.9%) compared to the predominantly intraluminal group (9/193, 4.7%, P = 0.008), there were no significant differences in outcomes of the EFTR procedure. No instances of recurrence were observed during the mean follow‐up period of 3.7 ± 2.3 years.EFTR was found to be feasible, safe, and effective for resecting upper GI SMTs, including lesions with predominantly extraluminal growth. Further validation in a prospective study is warranted. [ABSTRACT FROM AUTHOR]

Solitary primary extraosseous plasmacytoma is a rare disease in the gastrointestinal tract, recently classified as an "exceptional" tumor of the colon site. The real incidence (one case/population/year) is unknown but reasonably less than 1/10,000,000 cases/year with very few descriptions in the literature. The rare cases described in the literature are often diagnosed after surgery for perforation and with predominant localization of the left colon. The main endoscopic presentation mimics colon carcinoma with ulcerated mass and obstructing lumen. In this paper, we report a rare case of isolated mass mimicking a submucosal lesion of the ascending colon diagnosed in an older female patient by colonoscopy. The patient was almost asymptomatic; she reported only a history of hematochezia without anemia. This mass was successfully treated by surgery and followed by hematological investigations, including bone marrow biopsy, specific laboratory tests, and CT/PET scan, which confirmed primary isolated plasmacytoma of the colon. [ABSTRACT FROM AUTHOR]

Mixed neuroendocrine and non-neuroendocrine neoplasms, recently recognized in the WHO classification as (MiNEN), are rare tumors of the gastrointestinal tract. These tumors are composed of two distinct cellular components; a well- or poorly differentiated neuroendocrine tumor and a non-neuroendocrine tumor, usually in the form of an adenocarcinoma, either admixed with or adjacent to one another. A rarer phenotype is a tumor in which the endocrine and epithelial cell features occur within the same cell; i.e. amphicrine carcinoma. Herein, we report the case of an 80-year-old female patient who presented with melena, and who, on biopsy was diagnosed as amphicrine carcinoma that was mismatch repair deficient (MMRd) with loss of MLH1/PMS2 nuclear expression by immunohistochemistry. The histological and immunohistochemical findings of this rare entity are presented with review of pertinent literature. [ABSTRACT FROM AUTHOR]

Objective: Gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors in the gastrointestinal system, occurring frequently after epithelial tumors. Although rare, secondary epithelial malignancies can be associated with GISTs. It was planned to conduct a retrospective cohort study evaluating the coexistence of GISTs with malignancies and their long-term outcomes through clinical and pathological findings. Material and Methods: Demographic and clinicopathological data of 69 patients who underwent surgery for GIST between January 2011 and November 2021 were retrieved from the patient database. Variables between the groups with only GIST and those with a secondary malignancy alongside GIST were analyzed using the Chi-square test and Mann-Whitney U test. Long-term survival analyses were conducted using the Kaplan-Meier test. A p-value of <0.05 was considered statistically significant. Results: Out of the 69 patients in our population, 40 (58%) were male, and the median age was 65 years (interquartile range= 56-75). GIST was the most commonly located in the stomach (59.4%), and nine (13%) patients had a secondary malignancy. Tumor size, smooth muscle antibody (SMA), and S100 antibody expression showed significant differences between the groups (p< 0.001, p= 0.015, p= 0.006). Shorter survival was observed in patients with GIST plus secondary malignancy (p= 0.005). Conclusion: The incidence of other intraabdominal malignancies occurring alongside GISTs is more common than have been previously thought. While the presence of a secondary malignancy does not impact the overall survival (OS) in GISTs, it was observed that survival is dependent on the primary malignancy. Patients diagnosed with GISTs require thorough investigation and close monitoring for secondary malignancies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the clinical efficacy and safety of recombinant human vascular endostatin combined with compound Kushen injection by intraperitoneal infusion in the treatment of malignant peritoneal effusion of gastrointestinal tumors. METHODS: This study was a prospective study, 92 patients with malignant peritoneal effusion of gastrointestinal tumors admitted into the hospital from Aug. 2020 to Feb. 2023 were extracted to be divided into the control group (46 cases, 5-fluorouracil) and observation group (46 cases, recombinant human vascular endostatin + compound Kushen injection) according to the random number table method. After treatment of 3 weeks, the clinical efficacy, tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199), and carbohydrate antigen 125 (CA125)] levels and incidence of adverse drug reactions were compared between two groups. RESULTS: After 3 weeks of continuous peritoneal perfusion, the objective response rate in the observation group was higher than that in the control group [71. 74% (33/46) vs. 39. 13% (18/46)], with statically significant difference (P<0. 05). After treatment of 3 weeks, the serum tumor markers (CEA, CA199, and CA125) in two groups decreased, and the observation group was lower than the control group, with statically significant difference (P<0. 05). During the treatment period, the incidence of blood cytotoxicity in the observation group was 8. 70% (4/46), significantly lower than 32. 61% (15/46) in the control group, and the overall incidence of adverse drug reactions in the observation group were lower than that in control group [36. 96% (17/46) vs. 71. 74% (33/46)], with statically significant difference (P <0. 05). CONCLUSIONS: Recombinant human vascular endostatin combined with compound Kushen injection in the treatment of malignant peritoneal effusion of gastrointestinal tumors can effectively control disease progression, improve the clinical symptoms and disease prognosis of patients, with higher safety. [ABSTRACT FROM AUTHOR]

Introduction: Imatinib, a tyrosine kinase inhibitor, is the first-line therapy for patients with KIT mutation in gastrointestinal stromal tumor (GIST). Nausea, vomiting, diarrhea, dyspepsia and abdominal pain are common gastrointestinal adverse reactions of imatinib, but imatinib-induced ulcerative colitis (UC) is rarely reported. Case report: We presented a case of UC induced by imatinib in a 56-year-old male patient who experienced this adverse event after 5 years of imatinib 400 mg/d treatment following GIST resection. Management and outcome: The patient's diarrhea and bloody stools showed significant improvement following the discontinuation of imatinib therapy and administration of antidiarrheal medications. Then, imatinib was restarted at a daily dosage of 400 mg. Discussion: UC is a rare adverse event associated with imatinib. Physicians should consider the possibility of UC induced by imatinib when patients present with diarrhea and bloody stool after receiving imatinib treatment. This case offered objective evidence of UC induced by imatinib. [ABSTRACT FROM AUTHOR]

Purpose: The National Comprehensive Cancer Network guidelines state that the oxaliplatin dose of 85 mg/m2 used in various gastrointestinal cancer regimens may be infused over a rapid rate of 85 min instead of the standard time of 120 min. We evaluated the safety outcomes of rapid administration of oxaliplatin compared to standard infusion. Methods: We performed a retrospective, cohort study by chart review. Adult patients who received oxaliplatin as part of a FOLFOX, FOLFOXIRI, or FOLRINOX chemotherapy regimen from January 1, 2018, through June 30, 2021, were included. Primary outcomes were the incidence of hypersensitivity reaction (HSR) and treatment modification of oxaliplatin due to adverse drug events. Secondary outcomes included peripheral neuropathy (PN), myelosuppressive signs, and oxaliplatin-related emergency department visit and/or hospital admission. Results: A total of 178 patients were included (90 and 88 in the rapid-rate and standard-rate groups, respectively). Rapid-rate oxaliplatin was not associated with increased HSR or difference in toxicity requiring dose reduction, delayed dose, or slowed infusion rate, but was associated with increased rate of permanent discontinuation of oxaliplatin, 7.8% and 1.1% in the rapid-rate group and standard-rate groups, respectively (p = 0.032). Peripheral neuropathy occurred in 72.2% and 42% of patients in the rapid-rate group and standard-rate groups, respectively (relative risk for PN, 2.09; 95%, CI: 1.43–3.04; p <.001). There were no differences in any other adverse drug event measured. Conclusion: Rapid-rate oxaliplatin was associated with minimal treatment modifications; however, there was an increase in PN incidence. A faster rate of oxaliplatin administration may not be worth the increased risk of PN. [ABSTRACT FROM AUTHOR]

The article explores the use of neoadjuvant therapy, specifically peptide receptor radionuclide therapy (PRRT), for pancreatic neuroendocrine tumors (pNETs). pNETs are a type of tumor that has poorer outcomes compared to other neuroendocrine neoplasms. Neoadjuvant therapy has potential benefits in testing tumor biology, facilitating multimodal therapy, and down-staging tumors for improved resectability. However, there is limited research on neoadjuvant therapy for pNETs, and existing systemic therapies have shown low response rates. A recent study in Italy found that PRRT followed by surgery resulted in a radiological response rate of 59% for localized pNETs, with comparable postoperative outcomes to complex pancreatectomy for cancer. However, accurately identifying the extent of disease using preoperative imaging remains a challenge, and further research is needed to determine long-term oncological outcomes and the effectiveness of preoperative PRRT in reducing recurrence and prolonging survival. [Extracted from the article]

Introduction: For diagnosing malnutrition as an important modifiable risk factor in surgical cancer patients, GLIM criteria offer a standardised diagnostic pathway. Before assessing malnutrition, it is suggested to screen for malnutrition with an implemented screening tool, i.e., the NRS-2002. Validated data regarding the applied screening tool and its relevance for predicting outcome parameters in surgical patients is sparse. Methods: 260 patients undergoing major abdominal surgery for cancer were retrospectively analysed. Between January 2017 and December 2019, patients were prospectively screened for malnutrition with the Nutritional Risk Score 2002 (NRS). Irrespective of their screening result malnutrition was assessed with GLIM criteria using CT scan at lumbar level 3 for measuring skeletal muscle mass (GLIM MMCT). Patients with negative screening results (NRS ≤2) were analysed regarding their malnutrition assessment and outcome parameters. Results: Thirty four of 67 patients with NRS ≤2, posing no risk for malnutrition, were diagnosed malnourished according to GLIM MMCT (n = 34, 50.7%). 19 patients (55.9%) with NRS ≤2 and malnutrition according to GLIM had at least one complication, 12 patients (35.3%) had a severe complication (Clavien-Dindo grade ≥ 3a), in 26.5% re-laparotomy was necessary, readmission within 1 month in 20.6% of patients, and length of hospital stay was 18.76 ± 12.66, which was in total worse in outcome compared to the whole study group (n = 260). Patients with NRS ≤2 but diagnosed malnourished by GLIM were at significant higher risk to develop a severe complication (OR 2.256, 95% CI: 1.038–4.9095, p = 0.036) compared to patients with NRS ≤2 but not being diagnosed malnourished. The risk for overall complications was significantly increased in patients with malnutrition diagnosed by the GLIM criteria using MMCT (OR 2.028, 95% CI: 1.188–3.463, p = 0.009). Patients screened at risk with NRS ≥3 and diagnosed malnourished by GLIM were also at significant higher risk for developing complications (OR 1.728, 95% CI: 1.054–2.832, p = 0.029). Conclusion: GLIM MMCT is suitable for diagnosing malnutrition and estimating postoperative risk in gastrointestinal cancer patients. Nutritional assessment only in patients with NRS >2 may bear the risk to miss malnourished patients with high risk for poor clinical outcome. In every patient undergoing major cancer surgery, regular assessment of nutritional status regardless of screening result should be performed exploiting CT body composition analysis. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer (PC) is one of the most malignant cancers with a poor prognosis. Despite advances in the diagnosis and management of PC, the survival rate remains low. In Iran, the incidence of PC is increasing, with mortality rates nearly doubling over the past 25 years. Therefore, this study was designed to assess the temporal variations and incidence of PC in Golestan province, as a prominent hub for gastrointestinal cancers in Iran. Methods: In this cross-sectional study, patient information was obtained from the Golestan Population-Based Cancer Registry (GPCR) from 2006 to 2019. We calculated age-standardized incidence rates (ASRs) using the World standard population and reported the rates per 100000 persons-year. To compare ASRs across sexes and residence areas, incidence rate ratios (IRR) were calculated using Poisson regression models. We calculated the estimated annual percentage changes (EAPC) to assess time trends in incidence rates of PC in Golestan during the study period. Results: Among a total of 560 PC new cases (mean age of 63.72 years), 46.61% were diagnosed through clinical or paraclinical methods. The crude incidence rate and ASR were 2.24 and 2.95 (95% CI: 2.70-3.20) per 100000 persons-year, respectively. The ASR of PC was significantly higher in males (3.78; 95% CI: 3.37-4.19) than females (2.17; 95% CI: 1.88-2.46) (IRR=1.71; P<0.01). The ASR was higher in the urban (3.23; 95% CI: 2.88-3.58) compared to the rural population (2.65; 95% CI: 2.30-3.00) (IRR=1.23; P=0.02). The ASR of PC increased from 1.97 to 3.53 during 2006 to 2019 with an EAPC of 4.39 (95% CI: -3.56 to 12.75). The EAPCs were 4.85% and 4.37% in women and men, respectively. Conclusion: Our study showed that the incidence of PC is increasing in the Golestan province. Also, the incidence rate was higher in men, elderly people, and the urban population. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal cancer cells display both morphology and physiology diversity, thus posing a significant challenge for precise representation by a single data model. We conducted an in-depth study of gastrointestinal cancer heterogeneity by integrating and analyzing data from multiple modalities. Methods: We used a modified Canny algorithm to identify edges from tumor images, capturing intricate nonlinear interactions between pixels. These edge features were then combined with differentially expressed mRNA, miRNA, and immune cell data. Before data integration, we used the K-medoids algorithm to pre-cluster individual data types. The results of pre-clustering were used to construct the kernel matrix. Finally, we applied spectral clustering to the fusion matrix to identify different tumor subtypes. Furthermore, we identified hub genes linked to these subtypes and their biological roles through the application of Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Ontology (GO) enrichment analysis. Results: Our investigation categorized patients into three distinct tumor subtypes and pinpointed hub genes associated with each. Genes MAGI2-AS3, MALAT1, and SPARC were identified as having a differential impact on the metastatic and invasive capabilities of cancer cells. Conclusion: By harnessing multimodal features, our study enhances the understanding of gastrointestinal tumor heterogeneity and identifies biomarkers for personalized medicine and targeted treatments. [ABSTRACT FROM AUTHOR]

Context: Patients with cancer-related pain and concurrent substance use disorder (SUD) present a unique set of challenges for palliative care clinicians. A structured forum for interdisciplinary collaboration is needed to effectively manage this complex population. Objectives: Describe the feasibility and acceptability of a palliative care Complex Pain Board (CPB), an interdisciplinary team meeting to provide concrete care recommendations for patients with cancer-related pain and concurrent SUD and/or psychosocial complexity. Methods: We conducted a retrospective analysis of cases presented at CPB between May 2021 and June 2022 and a cross-sectional analysis of CBP participant surveys. Results: Among 28 cases included for analysis, gastrointestinal cancers (n = 7, 25.9%) and multiple myeloma (n = 5, 18.5%) were the most frequent cancer diagnoses. Primary reasons for referral were SUD (n = 22, 78.6%) and provider/team distress (n = 13, 46.4%). The most frequent recommendations made at CBP were encouraging interdisciplinary collaboration (n = 18, 64.3%), maintaining healthy boundaries (n = 15, 53.6%), and SUD management (n = 13, 46.4%). Of 14 scheduled meetings, most meetings involved the presentation of ≥1 cases (n = 12, 86%). Among 40 CBP participant surveys, most attendees (n = 38, 95%) were likely or highly likely to continue to attend. Conclusion: CPB is a feasible and acceptable intervention that allows for palliative care clinicians to collaborate and receive interdisciplinary team feedback and peer support on the management of patients with cancer-related pain and concurrent SUD and/or psychosocial complexity in the ambulatory care setting. Key Message: A regular, interdisciplinary team meeting (CPB) is a feasible and acceptable intervention to help palliative care clinicians manage challenging cases involving patients with cancer and concurrent SUD and/or psychosocial complexity. [ABSTRACT FROM AUTHOR]

Activating enhancer-binding protein 2 (AP-2) is a family of transcription factors (TFs) that play crucial roles in regulating embryonic and oncogenic development. In addition to splice isoforms, five major family members encoded by the TFAP2A/B/C/D/E genes have been identified in humans, i.e., AP-2α/β/γ/δ/ε. In general, the first three TFs have been studied more thoroughly than AP-2δ or AP-2ε. Currently, there is a relatively limited body of literature focusing on the AP-2 family in the context of gastroenterological research, and a comprehensive overview of the existing knowledge and recommendations for further research directions is lacking. Herein, we have collected available gastroenterological data on AP-2 TFs, discussed the latest medical applications of each family member, and proposed potential future directions. Research on AP-2 in gastrointestinal tumors has predominantly been focused on the two best-described family members, AP-2α and AP-2γ. Surprisingly, research in the past decade has highlighted the importance of AP-2ε in the drug resistance of gastric cancer (GC) and colorectal cancer (CRC). While numerous questions about gastroenterological disorders await elucidation, the available data undoubtedly open avenues for anti-cancer targeted therapy and overcoming chemotherapy resistance. In addition to gastrointestinal cancers, AP-2 family members (primarily AP-2β and marginally AP-2γ) have been associated with other health issues such as obesity, type 2 diabetes, liver dysfunction, and pseudo-obstruction. On the other hand, AP-2δ has been poorly investigated in gastroenterological disorders, necessitating further research to delineate its role. In conclusion, despite the limited attention given to AP-2 in gastroenterology research, pivotal functions of these transcription factors have started to emerge and warrant further exploration in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Soft tissue sarcomas (STSs) are rare cancers, making up less than 1% of all adult malignancies. Traditionally, the primary treatment for STS has been surgical resection. However, non-surgical approaches are becoming increasingly important in specific clinical situations. In this review, we explore the role of non-surgical treatments in managing STS, including their use as a bridge to surgery, as alternatives to surgery, for improving surgical outcomes, and for managing cases where surgery is not an option. Our findings highlight the effectiveness of these strategies in enhancing patient care and outcomes, providing a more personalized and less invasive approach to STS treatment. This review aims to advance the understanding and application of non-surgical methods in the treatment of soft tissue sarcomas. Mesenchymal tumors originate from mesenchymal cells and can be either benign or malignant, such as bone, soft tissue, and visceral sarcomas. Surgery is a cornerstone treatment in the management of mesenchymal tumors, often requiring complex procedures performed in high-volume referral centers. However, the COVID-19 pandemic has highlighted this need for alternative non-surgical approaches due to limited access to surgical resources. This review explores the role of non-surgical treatments in different clinical scenarios: for improving surgical outcomes, as a bridge to surgery, as better alternatives to surgery, and for non-curative treatment when surgery is not feasible. We discuss the effectiveness of active surveillance, cryoablation, high-intensity focused ultrasound, and other ablative techniques in managing these tumors. Additionally, we examine the use of tyrosine kinase inhibitors in gastrointestinal stromal tumors and hypofractionated radiotherapy in soft tissue sarcomas. The Sarculator tool is highlighted for its role in stratifying high-risk sarcoma patients and personalizing treatment plans. While surgery remains the mainstay of treatment, integrating advanced non-surgical strategies can enhance therapeutic possibilities and patient care, especially in specific clinical settings with limitations. A multidisciplinary approach in referral centers is vital to determine the optimal treatment course for each patient. [ABSTRACT FROM AUTHOR]

Simple Summary: The circadian clock controls the rhythmic timing of nearly every aspect of physiology, including sleep, body temperature, hormone fluctuation, and overall metabolism on a daily basis. Research shows that disruption to this control contributes to the development of diseases, including cancer. Evidence also suggests that cancers may be amenable to treatments that target the circadian clock, which maximizes benefits while minimizing side effects. Here, the rhythmic influence over cancers of the liver and gut will be reviewed, and treatments that take into account the circadian clock will be discussed. Circadian rhythms dictate the timing of cellular and organismal physiology to maintain homeostasis. Within the liver and gut, circadian rhythms influence lipid and glucose homeostasis, xenobiotic metabolism, and nutrient absorption. Disruption of this orchestrated timing is known to negatively impact human health and contribute to disease progression, including carcinogenesis. Dysfunctional core clock timing has been identified in malignant growths and may be used as a molecular signature of disease progression. Likewise, the circadian clock and its downstream effectors also represent potential for novel therapeutic targets. Here, the role of circadian rhythms in the pathogenesis of cancers of the liver and gut will be reviewed, and chronotherapy and chronopharmacology will be explored as potential treatment options. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to improve our understanding of gastrointestinal tract cancer and the side effects of cancer treatment by using advanced in vitro systems. Traditional models like cell cultures and animal studies provide valuable insights but have limitations in replicating the complexity of human disease and raise ethical concerns. By focusing on bioreactor-based in vitro systems, which can mimic the physical and chemical environment of the gastrointestinal tract, this study aims to provide more accurate models for studying cancer and its treatment side effects. These advancements could lead to better insights into disease mechanisms, potentially improving treatment strategies and benefiting the broader research community. Human diseases are multifaceted, starting with alterations at the cellular level, damaging organs and their functions, and disturbing interactions and immune responses. In vitro systems offer clarity and standardisation, which are crucial for effectively modelling disease. These models aim not to replicate every disease aspect but to dissect specific ones with precision. Controlled environments allow researchers to isolate key variables, eliminate confounding factors and elucidate disease mechanisms more clearly. Technological progress has rapidly advanced model systems. Initially, 2D cell culture models explored fundamental cell interactions. The transition to 3D cell cultures and organoids enabled more life-like tissue architecture and enhanced intercellular interactions. Advanced bioreactor-based devices now recreate the physicochemical environments of specific organs, simulating features like perfusion and the gastrointestinal tract's mucus layer, enhancing physiological relevance. These systems have been simplified and adapted for high-throughput research, marking significant progress. This review focuses on in vitro systems for modelling gastrointestinal tract cancer and the side effects of cancer treatment. While cell cultures and in vivo models are invaluable, our main emphasis is on bioreactor-based in vitro modelling systems that include the gut microbiome. [ABSTRACT FROM AUTHOR]

Simple Summary: Somatostatin analogs like lanreotide are considered first-line agents for the treatment of gastroenteropancreatic neuroendocrine tumors (NET). Although its effects on tumor proliferation and hormonal regulation are somewhat understood, its influence on the immune system has not been well elucidated. We used a double-pronged approach to understand the role of lanreotide in immune system regulation in healthy donor T cells in vitro as well as in vivo in cells obtained from 17 NET patients. We looked at cytokine signaling and differential gene expression to elucidate lanreotide's role in the treatment of NET through additional novel immune pathways. The CLARINET trial led to the approval of lanreotide for the treatment of patients with gastroenteropancreatic neuroendocrine tumors (NETs). It is hypothesized that lanreotide regulates proliferation, hormone synthesis, and other cellular functions via binding to somatostatin receptors (SSTR1–5) present in NETs. However, our knowledge of how lanreotide affects the immune system is limited. In vitro studies have investigated functional immune response parameters with lanreotide treatment in healthy donor T cell subsets, encompassing the breadth of SSTR expression, apoptosis induction, cytokine production, and activity of transcription factor signaling pathways. In our study, we characterized in vitro immune mechanisms in healthy donor T cells in response to lanreotide. We also studied the in vivo effects by looking at differential gene expression pre- and post-lanreotide therapy in patients with NET. Immune-focused gene and protein expression profiling was performed on peripheral blood samples from 17 NET patients and correlated with clinical response. In vivo, lanreotide therapy showed reduced effects on wnt, T cell receptor (TCR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling in CD8+ T cells in responders compared to non-responders. Compared to non-responders, responders showed reduced effects on cytokine and chemokine signaling but greater effects on ubiquitination and proteasome degradation genes. Our results suggest significant lanreotide pharmacodynamic effects on immune function in vivo, which correlate with responses in NET patients. This is not evident from experimental in vitro settings. [ABSTRACT FROM AUTHOR]

Simple Summary: The FGF/FGFR-mediated pathway coordinates the activity of VEGF/VEGFR signaling in IM-resistant GISTs. Mechanistically, FGF2 triggers the activation of the FGFR pathway, turns on the activation of VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. This was observed in IM-resistant GIST T-1R cells acquired IM resistance due to "RTK switch" (KIT loss/FGFR activation) and led to the impressive synergy scores between FGFR and VEGFR inhibitors, thereby providing a rationale to re-evaluate the effectiveness of combined anti-FGFR and VEGFR therapeutic strategies for GIST-acquired IM resistance via KIT-independent mechanisms. We showed previously that the autocrine activation of the FGFR-mediated pathway in GIST lacking secondary KIT mutations was a result of the inhibition of KIT signaling. We show here that the FGF2/FGFR pathway regulates VEGF-A/VEGFR signaling in IM-resistant GIST cells. Indeed, recombinant FGF2 increased the production of VEGF-A by IM-naive and resistant GIST cells. VEGF-A production was also increased in KIT-inhibited GIST, whereas the neutralization of FGF2 by anti-FGF2 mAb attenuated VEGFR signaling. Of note, BGJ 398, pan FGFR inhibitor, effectively and time-dependently inhibited VEGFR signaling in IM-resistant GIST T-1R cells, thereby revealing the regulatory role of the FGFR pathway in VEGFR signaling for this particular GIST cell line. This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. The high potency of the combined use of VEGFR and FGFR inhibitors in IM-resistant GISTs was revealed by the impressive synergy scores observed for regorafenib or sunitinib and BGJ 398. Moreover, FGFR1/2 and VEGFR1/2 were co-localized in IM-resistant GIST T-1R cells, and the direct interaction between the aforementioned RTKs was confirmed by co-immunoprecipitation. In contrast, IM-resistant GIST 430 cells expressed lower basal levels of FGF2 and VEGF-A. Despite the increased expression VEGFR1 and FGFR1/2 in GIST 430 cells, these RTKs were not co-localized and co-immunoprecipitated. Moreover, no synergy between FGFR and VEGFR inhibitors was observed for the IM-resistant GIST 430 cell line. Collectively, the dual targeting of FGFR and VEGFR pathways in IM-resistant GISTs is not limited to the synergistic anti-angiogenic treatment effects. The dual inhibition of FGFR and VEGFR pathways in IM-resistant GISTs potentiates the proapoptotic and anti-proliferative activities of the corresponding RTKi. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms. [ABSTRACT FROM AUTHOR]

This study aimed to assess the burden of early-onset gastrointestinal (GI) cancers in China over three decades. A comprehensive analysis was performed using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Data on early-onset GI cancers in 2020 and from 1990 to 2019 were extracted from GLOBOCAN 2020 database and GBD 2019, respectively. The average annual percent change (AAPC) was calculated to analyze the temporal trends using the Joinpoint Regression Program. The Bayesian age-period-cohort (BAPC) model was used to predict future trends up to 2030. In China, there were 185,980 incident cases and 119,116 deaths of early-onset GI cancer in 2020, with the highest incidence and mortality observed in liver cancer (new cases: 71,662; deaths: 62,412). The spectrum of early-onset GI cancers in China has transitioned over the last 30 years. The age-standardized rates of incidence, mortality, and disability-adjusted life years for colorectal and pancreatic cancers exhibited rapid increases (AAPC >0, P ≤ 0.001). The fastest-growing incidence rate was found in colorectal cancer (AAPC: 3.06, P < 0.001). Despite the decreases in liver, gastric, and esophageal cancers, these trends have been reversed or flattened in recent years. High body mass index was found to be the fastest-growing risk factor for early-onset GI cancers (estimated annual percentage change: 2.75–4.19, P < 0.05). Projection analyses showed an increasing trend in age-standardized incidence rates for almost all early-onset GI cancers during 2020–2030. The transitioning pattern of early-onset GI cancers in China emphasizes the urgency of addressing this public health challenge. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to improve the efficiency of daytime surgery for gastrointestinal polyp and ensure the safety of patients. We tried an information management method based on WeChat platform in patients undergoing daytime gastrointestinal polypectomy and to explore the feasibility and effectiveness of a full management model. Methods: Five hundred and ninety‐three patients were randomly divided into two groups: the control group was treated with traditional management methods and the experimental group was treated with the whole‐process management mode based on the WeChat platform. The WeChat platform‐based full management model included establishing a day surgery management WeChat group, developing multidisciplinary, full‐management protocols and processes for day surgery, establishing an information‐based surgical scheduling system and adopting diverse forms of day surgery education and continuity of care. This feature included illustrated brochures, vivid verbal presentations, WeChat public numbers and Internet management platforms. The treatment time, hospitalization cost and patient satisfaction of the two groups were counted. Results: In the experimental group, 408 patients were enrolled. The preoperative waiting time and patients' length of stay were 3 days and 1 day, respectively. The medical and nursing intake time was 7 min. The procedure cancellation rate and postoperative complications rate was 0.07% and 0.02%. In the control group, 185 patients were enrolled in the study, The preoperative waiting time and patients' length of stay was 7 days and 3 days. The medical and nursing intake time was 28 min. The procedure cancellation rate and postoperative complications rate were 0.13% and 0.05%, respectively. The hospitalization costs were reduced by an average of $140/person and the satisfaction scores were higher than the control group. In summary, the preoperative waiting time, medical reception time, surgical cancellation rate, length of hospital stay and hospitalization cost in the observation group were less than those in the control group (p < 0.05). Patient satisfaction scores were significantly higher than those in the control group (p < 0.05). Conclusion: Through the full management model based on WeChat, the preoperative waiting time, medical reception time, surgical cancellation rate, length of hospital stay and hospitalization cost in the experimental group were less than those in the control group. Patient satisfaction scores were significantly higher than those in the control group and the difference was statistically significant. [ABSTRACT FROM AUTHOR]