Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

INTRODUCTION: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract.

One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.

UMobileNetV2 model for semantic segmentation of gastrointestinal tract in MRI scans.

Gastrointestinal (GI) cancer is leading general tumour in the Gastrointestinal tract, which is fourth significant reason of tumour death in men and women. The common cure for GI cancer is radiation treatment, which contains directing a high-energy X-ray beam onto the tumor while avoiding healthy organs. To provide high dosages of X-rays, a system needs for accurately segmenting the GI tract organs. The study presents a UMobileNetV2 model for semantic segmentation of small and large intestine and stomach in MRI images of the GI tract. The model uses MobileNetV2 as an encoder in the contraction path and UNet layers as a decoder in the expansion path. The UW-Madison database, which contains MRI scans from 85 patients and 38,496 images, is used for evaluation. This automated technology has the capability to enhance the pace of cancer therapy by aiding the radio oncologist in the process of segmenting the organs of the GI tract. The UMobileNetV2 model is compared to three transfer learning models: Xception, ResNet 101, and NASNet mobile, which are used as encoders in UNet architecture. The model is analyzed using three distinct optimizers, i.e., Adam, RMS, and SGD. The UMobileNetV2 model with the combination of Adam optimizer outperforms all other transfer learning models. It obtains a dice coefficient of 0.8984, an IoU of 0.8697, and a validation loss of 0.1310, proving its ability to reliably segment the stomach and intestines in MRI images of gastrointestinal cancer patients.

Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.

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.

Pathways and molecules for overcoming immunotolerance in metastatic gastrointestinal tumors.

Worldwide, gastrointestinal (GI) cancer is recognized as one of the leading malignancies diagnosed in both genders, with mortality largely attributed to metastatic dissemination. It has been identified that in GI cancer, a variety of signaling pathways and key molecules are modified, leading to the emergence of an immunotolerance phenotype. Such modifications are pivotal in the malignancy's evasion of immune detection. Thus, a thorough analysis of the pathways and molecules contributing to GI cancer's immunotolerance is vital for advancing our comprehension and propelling the creation of efficacious pharmacological treatments. In response to this necessity, our review illuminates a selection of groundbreaking cellular signaling pathways associated with immunotolerance in GI cancer, including the Phosphoinositide 3-kinases/Akt, Janus kinase/Signal Transducer and Activator of Transcription 3, Nuclear Factor kappa-light-chain-enhancer of activated B cells, Transforming Growth Factor-beta/Smad, Notch, Programmed Death-1/Programmed Death-Ligand 1, and Wingless and INT-1/beta-catenin-Interleukin 10. Additionally, we examine an array of pertinent molecules like Indoleamine-pyrrole 2,3-dioxygenase, Human Leukocyte Antigen G/E, Glycoprotein A Repetitions Predominant, Clever-1, Interferon regulatory factor 8/Osteopontin, T-cell immunoglobulin and mucin-domain containing-3, Carcinoembryonic antigen-related cell adhesion molecule 1, Cell division control protein 42 homolog, and caspases-1 and -12.

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.

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.

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.

Alteration in DNA methylation patterns: Epigenetic signatures in gastrointestinal cancers.

Abnormalities in epigenetic modifications can cause malignant transformations in cells, leading to cancers of the gastrointestinal (GI) tract, which accounts for 20% of all cancers worldwide. Among the epigenetic alterations, DNA hypomethylation is associated with genomic instability. In addition, CpG methylation and promoter hypermethylation have been recognized as biomarkers for different malignancies. In GI cancers, epigenetic alterations affect genes responsible for cell cycle control, DNA repair, apoptosis, and tumorigenic-specific signaling pathways. Understanding the pattern of alterations in DNA methylation in GI cancers could help scientists discover new molecular-based pharmaceutical treatments. This study highlights alterations in DNA methylation in GI cancers. Understanding epigenetic differences among GI cancers may improve targeted therapies and lead to the discovery of new diagnostic biomarkers.

Expression of TGF-ß1 in Gastrointestinal Stromal Tumor (GIST) and the Occurrence of Frequent Desmoplasia.

Gastrointestinal stromal tumors (GISTs) are mesenchymal neoplasms with variable behavior characterized by differentiation toward the interstitial cells of Cajal occurring anywhere in the gastrointestinal stromal tract. Frequently, GISTs have fibrous stroma within tumor cell proliferation areas, which is unlike other types of malignant tumors. If this desmoplasia is active, there is a possibility that some sort of transmitter exists between GIST cells and cells related to fibrosis in the tumor cell proliferation areas. Transforming growth factor (TGF)-ß isoforms, particularly TGF-ß1, are critical for fibrosis pathogenesis. TGF-ß1 regulation of myofibroblasts and fibroblasts during fibrosis is well described. The induced fibroblast activation resulting in myofibroblast differentiation has been reported as an important source of collagen, glycoproteins, proteoglycans, and matrix metallopeptidases in wound healing and fibrosis. However, there are a few reports on the relationship between TGF-ß1 and GISTs. This study aims to clarify TGF-ß1 expression in 30 gastric GISTs using immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). For comparison, we also enrolled 30 samples of gastric tubular adenocarcinoma (GTAC). We confirmed TGF-ß1 expression (H-score ≥50 points) in 57% of GIST and 13% of GTAC samples, a significant difference between the 2 tumor types ( P =0.001). We examined the TGF-ß1 mRNA expression of 3 representative GIST samples, each having their respective immunostained areas detected by RT-PCR. Finding TGF-ß1 expression may indicate that this cytokine plays a part in the formation of desmoplasia within GIST cell proliferative areas.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

Emerging trends in gastrointestinal cancers: Targeting developmental pathways in carcinogenesis and tumor progression.

Gastrointestinal carcinomas are a group of cancers associated with the digestive system and its accessory organs. The most prevalent cancers related to the gastrointestinal tract are colorectal, gall bladder, gastric, hepatocellular, and esophageal cancers, respectively. Molecular aberrations in different signaling pathways, such as signal transduction systems or developmental pathways are the chief triggering mechanisms in different cancers Though a massive advancement in diagnostic and therapeutic interventions results in improved survival of patients with gastrointestinal cancer; the lower malignancy stages of these carcinomas are comparatively asymptomatic. Various gastrointestinal-related cancers are detected at advanced stages, leading to deplorable prognoses and increased rates of recurrence. Recent molecular studies have elucidated the imperative roles of several signaling pathways, namely Wnt, Hedgehog, and Notch signaling pathways, play in the progression, therapeutic responsiveness, and metastasis of gastrointestinal-related cancers. This book chapter gives an interesting update on recent findings on the involvement of developmental signaling pathways their mechanistic insight in gastrointestinalcancer. Subsequently, evidences supporting the exploration of gastrointestinal cancer related molecular mechanisms have also been discussed for developing novel therapeutic strategies against these debilitating carcinomas.

S100 protein family: Emerging role and mechanism in digestive tract cancer (Review).

Digestive tract cancer is one of the most common types of cancers globally, with ~4.8 million new cases and 3.4 million cancer­associated deaths in 2018, accounting for 26% of cancer incidence and 35% of cancer­related deaths worldwide. S100 protein family is involved in regulating cancer cell proliferation, angiogenesis, epithelial­mesenchymal transition (EMT), metastasis, metabolism and immune microenvironment homeostasis. The critical role of S100 protein family in digestive tract cancer involves complicated mechanisms, such as cancer stemness remodeling, anaerobic glycolysis regulation, tumor­associated macrophage differentiation and EMT. The present study systematically reviewed published studies on the compositions, function and the underlying molecular mechanisms of the S100 family, as well as guidance for diagnosis, treatment and prognosis of digestive tract cancer. Systematic review of the roles and underlying molecular mechanisms of S100 protein family may provide new insight into exploring potential cancer biomarkers and the optimized therapeutic strategies for digestive tract cancer.

Mechanism of metal ion-induced cell death in gastrointestinal cancer.

Gastrointestinal (GI) cancer is one of the most severe types of cancer, with a significant impact on human health worldwide. Due to the urgent demand for more effective therapeutic strategies against GI cancers, novel research on metal ions for treating GI cancers has attracted increasing attention. Currently, with accumulating research on the relationship between metal ions and cancer therapy, several metal ions have been discovered to induce cell death. In particular, the three novel modes of cell death, including ferroptosis, cuproptosis, and calcicoptosis, have become focal points of research in the field of cancer. Meanwhile, other metal ions have also been found to trigger cell death through various mechanisms. Accordingly, this review focuses on the mechanisms of metal ion-induced cell death in GI cancers, hoping to provide theoretical support for further GI cancer therapies.

[Gastrointestinal stromal tumors : Where do we stand?] / Gastrointestinale Stromatumoren : Wo stehen wir?

For more than 20 years gastrointestinal stromal tumors (GIST) have been a paradigm for a targeted treatment with tyrosine kinase inhibitors. A fundamental prerequisite for a neoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of a hereditary or syndromic predisposition must be considered because this results in consequences for the treatment and a different follow-up strategy.

Retrospective Analyses of PD-L1, LAG-3, TIM-3, OX40L Expressions and MSI Status in Gastroenteropancreatic Neuroendocrine Neoplasms.

We investigated expressions of PD-L1, LAG-3, TIM-3, and OX40L as immune checkpoint proteins, and MSI (repetitive short-DNA-sequences due to defective DNA-repair system) status were analyzed with immunohistochemistry from tissue blocks. Of 83 patients, PD-L1 expression was observed in 18.1% (n = 15) of the patients. None of the patients exhibited LAG-3 expression. TIM-3 expression was 4.9% (n = 4), OX40L was 22.9% (n = 19), and 8.4% (n = 7) of the patients had MSI tumor. A low-to-intermediate positive correlation was observed between PD-L1 and TIM-3 expressions (rho: 0.333, p < 0.01). Although PD-L1 expression was higher in grade 3 NET/NEC, MSI status was prominent in grade 1/2 NET.

Risk factors for positive resection margins after endoscopic resection for gastrointestinal neuroendocrine tumors.

BACKGROUND: In recent years, the incidence of gastrointestinal neuroendocrine tumors (GI-NETs) has remarkably increased due to the widespread use of screening gastrointestinal endoscopy. Currently, the most common treatments are surgery and endoscopic resection. Compared to surgery, endoscopic resection possesses a higher risk of resection margin residues for the treatment of GI-NETs. METHODS: A total of 315 patients who underwent surgery or endoscopic resection for GI-NETs were included. We analyzed their resection modality (surgery, ESD, EMR), margin status, Preoperative marking and Prognosis. RESULTS: Among 315 patients included, 175 cases underwent endoscopic resection and 140 cases underwent surgical treatment. A total of 43 (43/175, 24.57%) and 10 (10/140, 7.14%) patients exhibited positive resection margins after endoscopic resection and surgery, respectively. Multivariate regression analysis suggested that no preoperative marking and endoscopic treatment methods were risk factors for resection margin residues. Among the patients with positive margin residues after endoscopic resection, 5 patients underwent the radical surgical resection and 1 patient underwent additional ESD resection. The remaining 37 patients had no recurrence during a median follow-up of 36 months. CONCLUSIONS: Compared with surgery, endoscopic therapy has a higher margin residual rate. During endoscopic resection, preoperative marking may reduce the rate of lateral margin residues, and endoscopic submucosal dissection may be preferred than endoscopic mucosal resection. Periodical follow-up may be an alternative method for patients with positive margin residues after endoscopic resection.

Controllers of histone methylation-modifying enzymes in gastrointestinal cancers.

Gastrointestinal (GI) cancers have been considered primarily genetic malignancies, caused by a series of progressive genetic alterations. Accumulating evidence shows that histone methylation, an epigenetic modification program, plays an essential role in the different pathological stages of GI cancer progression, such as precancerous lesions, tumorigenesis, and tumor metastasis. Histone methylation-modifying enzymes, including histone methyltransferases (HMTs) and demethylases (HDMs), are the main executor of post-transcriptional modification. The abnormal expression of histone methylation-modifying enzymes characterizes GI cancers with complex pathogenesis and progression. Interactions between upstream controllers and histone methylation-modifying enzymes have recently been revealed, and have provided numerous opportunities to elucidate the pathogenesis of GI cancers in depth and clearly. Here we focus on the association between histone methylation-modifying enzymes and their controllers, aiming to provide a new perspective on the molecular research and clinical management of GI cancers.