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Purpose . This review aims to highlight current improvements in microfluidic devices designed for digestive cancer simulation. The review emphasizes the use of multicellular 3D tissue engineering models to understand the complicated biology of the tumor microenvironment (TME) and cancer progression. The purpose is to develop oncology research and improve digestive cancer patients' lives. Methods . This review analyzes recent research on microfluidic devices for mimicking digestive cancer. It uses tissue-engineered microfluidic devices, notably organs on a chip (OOC), to simulate human organ function in the lab. Cell cultivation on modern three-dimensional hydrogel platforms allows precise geometry, biological components, and physiological qualities. The review analyzes novel methodologies, key findings, and technical progress to explain this field's advances. Results . This study discusses current advances in microfluidic devices for mimicking digestive cancer. Micro physiological systems with multicellular 3D tissue engineering models are emphasized. These systems capture complex biochemical gradients, niche variables, and dynamic cell-cell interactions in the tumor microenvironment (TME). These models reveal stomach cancer biology and progression by duplicating the TME. Recent discoveries and technology advances have improved our understanding of gut cancer biology, as shown in the review. Conclusion . Microfluidic systems play a crucial role in modeling digestive cancer and furthering oncology research. These platforms could transform drug development and treatment by revealing the complex biology of the tumor microenvironment and cancer progression. The review provides a complete summary of recent advances and suggests future research for field professionals. The review's major goal is to further medical research and improve digestive cancer patients' lives., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

Objective: To systematically evaluate the efficacy and safety of anlotinib targeted therapy for the treatment of patients with advanced digestive system neoplasms (DSNs)., Methods: Clinical trials were extracted from PubMed, the Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and the Wanfang database up to October 2023. Outcome measures, including therapeutic efficacy, quality of life (QOL) and adverse events, were extracted and evaluated., Results: Twenty trials, including 1,613 advanced DSNs patients, were included. The results indicated that, compared with conventional treatment alone, the combination of anlotinib targeted therapy with conventional treatment significantly improved the patients' 6-months overall survival (OS, OR=1.76, CI=1.53 to 2.02, P <0.00001), overall response (ORR, OR=1.76, CI=1.53 to 2.02, P <0.00001) and disease control rate (DCR, OR=1.51, 95% CI=1.25 to 1.84, P <0.0001). Moreover, the group that received the combined therapy had higher rates of hypertension ( P <0.00001), proteinuria ( P <0.00001), fatigue ( P <0.00001), diarrhea ( P <0.00001), hypertriglyceridemia ( P =0.02), alanine aminotransfease (ALT)increased ( P =0.004), aspartate transaminase (AST) increased ( P =0.006), anorexia ( P <0.00001), weight loss ( P =0.002), abdominal pain ( P =0.0006), hypothyroidism ( P =0.02), prolonged QT interval ( P =0.04). Analyses of other adverse events, such as gastrointestinal reaction, leukopenia, and neutropenia, did not reveal significant differences ( P >0.05)., Conclusion: The combination of anlotinib targeted therapy and conventional treatment is more effective for DSNs treatment than conventional treatment alone. However, this combined treatment could lead to greater rates of hypertension, albuminuria and hand-foot syndrome. Therefore, the benefits and risks should be considered before treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhou, Wang, Mu and Meng.)

Competing Interests: Competing interests: None declared.

Background: Accurate prognostic stratification of hepatocellular carcinoma (HCC) is vital for clinical trial enrollment and treatment allocation. Multiple scoring systems have been created to predict patient survival, but no standardized scoring systems account for radiologic tumor features. We sought to create a generalizable scoring system for HCC which incorporates standardized radiologic tumor features and more accurately predicts overall survival (OS) than established systems., Methods: Clinicopathologic parameters were collected from a prospectively collected cohort of patients with HCC treated at a single institution. Imaging studies were evaluated for tumor characteristics. Patients were randomly divided into a training set for identification of covariates that impacted OS and a validation set. Cox models were used to determine the association of various factors with OS and a scoring system was created., Results: We identified 383 patients with HCC with imaging and survival outcomes, n = 255 in the training set and 128 in the validation cohort. Factors associated with OS on multivariate analysis included: tumor margin appearance on CT or MRI (hazard ratio [HR] 1.37, 95% CI, 1.01-1.88) with infiltrative margins portending worse outcomes than encapsulated margins, massive tumor morphology (HR 1.64, 95% CI, 1.06-2.54); >2 lesions (HR 2.06, 95% CI, 1.46-2.88), Child-Turcotte-Pugh class C (HR 3.7, 95% CI, 2.23-6.16), and portal vein thrombus (HR 2.41, 95% CI, 1.71-3.39). A new scoring system was developed and more predictive of OS than other well-established systems., Conclusions: Incorporation of standardized imaging characteristics to established clinical and lab predictors of outcome resulted in an improved predictive scoring system for patients with HCC., (© The Author(s) 2023. Published by Oxford University Press.)

Chromatin remodeling is a critical step in the DNA damage response, and the ATP-dependent chromatin remodelers are a group of epigenetic regulators that alter nucleosome assembly and regulate transcription factor accessibility to DNA, preventing genomic instability and tumorigenesis caused by DNA damage. The SWI/SNF chromatin remodeling complex is one of them, and mutations in the gene encoding the SWI/SNF subunit are frequently found in digestive tumors. We review the most recent literature on the role of SWI/SNF complexes in digestive tumorigenesis, with different SWI/SNF subunits playing different roles. They regulate the biological behavior of tumor cells, participate in multiple signaling pathways, interact with multiple genes, and have some correlation with the prognosis of patients. Their carcinogenic properties may help discover new therapeutic targets. Understanding the mutations and defects of SWI/SNF complexes, as well as the underlying functional mechanisms, may lead to new strategies for treating the digestive system by targeting relevant genes or modulating the tumor microenvironment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Gastric cancer is one of the most frequent and deadly tumours worldwide. However, the evidence that currently exists for the treatment of older adults is limited and is derived mainly from clinical trials in which older patients are poorly represented. In this article, a group of experts selected from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Group for the Treatment of Digestive Tumours (TTD), and the Spanish Multidisciplinary Group on Digestive Cancer (GEMCAD) reviews the existing scientific evidence for older patients (≥65 years old) with gastric cancer and establishes a series of recommendations that allow optimization of management during all phases of the disease. Geriatric assessment (GA) and a multidisciplinary approach should be fundamental parts of the process. In early stages, endoscopic submucosal resection or laparoscopic gastrectomy is recommended depending on the stage. In locally advanced stage, the tolerability of triplet regimens has been established; however, as in the metastatic stage, platinum- and fluoropyrimidine-based regimens with the possibility of lower dose intensity are recommended resulting in similar efficacy. Likewise, the administration of trastuzumab, ramucirumab and immunotherapy for unresectable metastatic or locally advanced disease is safe. Supportive treatment acquires special importance in a population with different life expectancies than at a younger age. It is essential to consider the general state of the patient and the psychosocial dimension., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background: Rab1A not only regulates eukaryotic secretion, autophagy and intracellular traffic, but also extensively participates in the development of cancer. Thus, we collected data to investigate the clinical value of Rab1A in cancers., Methods: English web database was searched for appropriate studies. The role of Rab1A in cancer patients was evaluated by combining hazard ratios and odds ratios., Results: There were 15 studies in 14 articles, including 1,791 cancer patients. The results showed that upregulated Rab1A led to poor prognosis in cancer patients (pooled HR = 2.545, 95% CI = 1.924 - 3.367, p < 0.001). Notably, a high level of Rab1A was associated with a poorer prognosis than patients with a low level of Rab1A in digestive system cancer (pooled HR = 2.484, 95% CI = 1.796 - 3.437, p < 0.001). In order to explore the possible carcinogenic mechanism, we further analyzed and confirmed that high expression of Rab1A was associated with worse histologic grade, deeper tumor invasion, higher TNM stage, positive LN metastasis, positive neural invasion, positive vascular invasion, and larger tumor size (p < 0.05)., Conclusions: Rab1A overexpression was associated with poor prognosis and adverse clinicopathological parameters in cancer patients and had the potential to be a target for future cancer therapy.

Objectives: Muscle weakness, assessed by grip strength, has been shown to predict postoperative mortality in older patients with cancer. Because lower extremity muscle strength well reflects physical performance, we examined whether lower knee extension muscle strength predicts postoperative mortality better than grip strength in older patients with gastrointestinal cancer., Design: Prospective, observational study in a single institution., Setting and Participants: A total of 813 patients (79.0 ± 4.2 years, 66.5% male) aged 65 years or older with gastrointestinal cancer who underwent preoperative evaluation of grip strength and isometric knee extension muscle strength between April 2012 and April 2019 were included., Methods: The study participants were prospectively followed up for postoperative mortality. Muscle weakness was defined as the lowest quartile of grip strength or knee extension strength (GS-muscle weakness and KS-muscle weakness, respectively)., Results: Among the study participants, 176 patients died during a median follow-up of 716 days. In the Kaplan-Meier analysis, we found that patients with both GS-muscle weakness and KS-muscle weakness had a lower survival rate than those without muscle weakness. As expected, higher clinical stages and abdominal and thoracic surgeries compared with endoscopic surgery were associated with increased all-cause mortality. In addition, we found that KS-muscle weakness, but not GS-muscle weakness, was an independent prognostic factor after adjusting for sex, body mass index, cancer stage, surgical technique, and surgical site in the Cox proportional hazard model., Conclusions and Implications: In older patients with gastrointestinal cancer, muscle weakness based on knee extension muscle strength can be a better predictor of postoperative prognosis than muscle weakness based on grip strength., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers., Methods: We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307)., Results: A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50-2.03), 1.96 (95% CI: 1.58-2.44), and 1.81 (95% CI: 1.49-2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers., Conclusion: TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding., (© 2023. The Author(s).)

Few studies have been designed to investigate the effect of serum choline on the risk of incident cancer. This study aims to explore the association between serum choline and the risk of new-onset cancer. We conducted a case-control study, including 199 patients with incident cancer and 199 matched controls during a median of 3.9 years of follow-up, nested within the China Stroke Primary Prevention Trial. Cubic spline regression (RCS) and conditional logistic regression analysis was used to assess the association of serum choline and incident cancer risk. We observed a positive dose-response association between serum choline levels and the risk of overall (p for overall = 0.046) and digestive system cancer (p for overall = 0.039). Compared with patients with the lowest choline levels (Q1 group), patients in the highest levels of choline (Q4) had a 3.69-fold and 6.01-fold increased risk of overall (OR = 3.69, 95% CI 1.17-11.63) and digestive system cancer (OR = 6.01, 95% CI 1.14-31.67). Elevated choline levels (per SD, 11.49 μg/mL) were associated with a higher risk of overall cancer among participants who were older, male, and smokers in the subgroup analyses. We found a positive association between elevated levels of serum choline with increased risk of incident cancer. Our findings have critical clinical implications for cancer prevention and diagnosis.Trial registration CSPPT, NCT00794885. Registered: November 20, 2008. https://www.clinicaltrials.gov/ct2/show/study/NCT00794885 https://www.clinicaltrials.gov/ct2/show/study/NCT00794885., (© 2023. The Author(s).)

Non-cancer deaths are now becoming a great threat to the health of cancer survivors. There are no comprehensive and systematic reports on chronic liver disease and cirrhosis mortality (CLDCM) among patients with digestive system cancers (DSCs). This research aimed to quantitatively assess the risks and patterns of CLDCM among patients with DSCs. From the surveillance, epidemiology and end results (SEER) program, we extracted the data of patients diagnosed with DSCs between 2000 and 2017. Trends in incidence-based mortality rate (IBMR) were calculated using Joinpoint software. The standardized mortality ratio (SMR) was obtained based on the reference of the general United States population. The cumulative incidence function curves were constructed by all causes of death. Independent indicators were identified using the multivariate Fine and Gray competing risk model. We included 906,292 eligible patients from the SEER program, of which 3068 (0.34%) died from chronic liver disease and cirrhosis (CLDC). The IBMR of CLDC continued to increase during the study period [average annual percent change (APC): 6.7%; 95% confidence interval (CI) 5.1-8.2] and the SMR was significantly increased (SMR: 3.19; 95% CI 3.08-3.30). The cumulative mortality of CLDC was the lowest in all causes of death. Furthermore, the age at diagnosis, race, gender, marital status, year of diagnosis, SEER stage, surgery, chemotherapy and radiotherapy were identified as independent indicators. Better screening, diagnostic and management approaches need to be implemented as a preferred method to protect the liver among patients with DSCs., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Polygenic risk scores (PRSs) have been used to stratify colorectal cancer (CRC) risk in the general population, whereas its role in Lynch syndrome (LS), the most common type of hereditary CRC, is still conflicting. We aimed to assess the ability of PRS to refine CRC risk prediction in European-descendant individuals with LS., Methods: 1465 individuals with LS (557 MLH1 , 517 MSH2/EPCAM , 299 MSH6 and 92 PMS2 ) and 5656 CRC-free population-based controls from two independent cohorts were included. A 91-SNP PRS was applied. A Cox proportional hazard regression model with 'family' as a random effect and a logistic regression analysis, followed by a meta-analysis combining both cohorts were conducted., Results: Overall, we did not observe a statistically significant association between PRS and CRC risk in the entire cohort. Nevertheless, PRS was significantly associated with a slightly increased risk of CRC or advanced adenoma (AA), in those with CRC diagnosed <50 years and in individuals with multiple CRCs or AAs diagnosed <60 years., Conclusion: The PRS may slightly influence CRC risk in individuals with LS in particular in more extreme phenotypes such as early-onset disease. However, the study design and recruitment strategy strongly influence the results of PRS studies. A separate analysis by genes and its combination with other genetic and non-genetic risk factors will help refine its role as a risk modifier in LS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

While constitutional pathogenic variants in the APC gene cause familial adenomatous polyposis, APC c.3920T>A; p.Ile1307Lys (I1307K) has been associated with a moderate increased risk of colorectal cancer (CRC), particularly in individuals of Ashkenazi Jewish descent. However, published data include relatively small sample sizes, generating inconclusive results regarding cancer risk, particularly in non-Ashkenazi populations. This has led to different country/continental-specific guidelines regarding genetic testing, clinical management and surveillance recommendations for I1307K. A multidisciplinary international expert group endorsed by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT), has generated a position statement on the APC I1307K allele and its association with cancer predisposition. Based on a systematic review and meta-analysis of the evidence published, the aim of this document is to summarise the prevalence of the APC I1307K allele and analysed the evidence of the associated cancer risk in different populations. Here we provide recommendations on the laboratory classification of the variant, define the role of predictive testing for I1307K, suggest recommendations for cancer screening in I1307K heterozygous and homozygous individuals and identify knowledge gaps to be addressed in future research studies. Briefly, I1307K, classified as pathogenic, low penetrance, is a risk factor for CRC in individuals of Ashkenazi Jewish origin and should be tested in this population, offering carriers specific clinical surveillance. There is not enough evidence to support an increased risk of cancer in other populations/subpopulations. Therefore, until/unless future evidence indicates otherwise, individuals of non-Ashkenazi Jewish descent harbouring I1307K should be enrolled in national CRC screening programmes for average-risk individuals., Competing Interests: Competing interests: BH is an employee and shareholder of Invitae Corp., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Different ages for diagnosis of diabetes have diverse effects on risks of cardiovascular disease, dementia, and mortality, but there is little evidence of cancer. This study investigated the relationship between diabetes at different diagnostic ages and risks of cancer incidence and mortality in people aged 37-73 years., Methods: Participants with diabetes in the UK Biobank prospective cohort were divided into four groups: ≤40, 41-50, 51-60, and >60 years according to age at diagnosis. A total of 26,318 diabetics and 105,272 controls (1:4 randomly selected for each diabetic matched by the same baseline age) were included. We calculated the incidence density, standardized incidence, and mortality rates of cancer. Cox proportional hazard model was used to examine the associations of diabetes at different diagnostic ages with cancer incidence and mortality, followed by subgroup analyses., Results: Compared to corresponding controls, standardized incidence and mortality rates of overall and digestive system cancers were higher in diabetes diagnosed at age 41-50, 51-60, and >60 years, especially at 51-60 years. Individuals diagnosed with diabetes at different ages were at higher risk to develop site-specific cancers, with a prominently increased risk of liver cancer since the diagnosis age of >40 years. Significantly, participants with diabetes diagnosed at 51-60 years were correlated with various site-specific cancer risks [hazard ratio (HR) for incidence: 1.088-2.416, HR for mortality: 1.276-3.269]. Moreover, for mortality of digestive system cancers, we observed an interaction effect between smoking and diabetes diagnosed at 51-60 years., Conclusion: Our findings highlighted that the age at diagnosis of diabetes, especially 51-60 years, was critical risks of cancer incidence and mortality and may represent a potential preventative window for cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peng, Liu, Wang, Qiao, Si, Wang, Gong, Zhou, Song and Song.)

Neoplasms are one of the most concerned public health problems worldwide. Digestive system neoplasms, with a high morbidity and mortality, is one of the most common malignant tumors in human being. It is found that exosomes act as an intercellular communication media to carry the metabolic and genetic information of parental cells to target cells. Likely, exosomes participate in lipid metabolism and regulates multiple processes in digestive system neoplasms, including the information transmission among cancer cells, the formation of neoplastic microenvironment, and the neoplastic biological behaviors like metastasis, invasion, and the chemotherapy resistance. In this review, we firstly introduce the main mechanisms whereas exosomes act as intercellular lipometabolic communication mediator in digestive system neoplasms. Thereafter we introduce the relationship between exosomes lipid metabolism and various type of digestive system neoplasms, including gastric cancer, hepatocellular carcinoma, pancreatic cancer, and colorectal cancer. Eventually, we summarized and prospected the development and implication of exosomes in digestive system neoplasms. The further research of exosomes as intercellular lipid metabolism mediator will contribute to accurate and efficient diagnosis and treatment of digestive system neoplasms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Cancer has currently become a serious public health issue in many countries worldwide, and tumors of the digestive system have attracted an increasing number of researchers' due to their numerous types, high proportion and wide area of occurrence. While tumors of the digestive system suffer from high mortality rates, leading to untimely diagnosis and a poor prognosis, making it necessary to update current treatment approaches such as surgery, radiation therapy, and chemotherapy. This highlights the importance of exploring novel therapeutic ideas and targets. Traditional Chinese medicine has a long history of clinical use due to its low toxicity and multi-factor targeting of multiple pathways. As a kind of traditional Chinese herb, S. nigrum Linn. is highly regarded for its proven antitumor activity. The aim of this study was to comprehensively recapitulate and analyze the anti-cancer effects and molecular mechanisms of treatment of gastrointestinal tumors with S. nigrum Linn. extracts and related compounds, including classical signaling pathways mediated by them as well as noncoding RNA pathways associated with tumor suppression. Components that have been found to be responsible for the anti-cancer activity of S. nigrum Linn. include solanine, solasonine, solamargine, a-L-rhhamnopyranose, uttroside B, degalactotigonin, glycoprotein, and other compounds. The underlying mechanisms of anti-cancer activity reflected in this study include apoptosis, cell cycle arrest, autophagy, anti-angiogenesis, suppression of metastasis and invasion, immune escape, and increased sensitivity to radiotherapy. S. nigrum Linn. has great potential in the treatment of tumors of the digestive system, and through further clinical trials and pharmacological mechanisms it has the potential to become a uniform and standardized anti-tumor drug., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Laparoscopic resection has been reported as effective and safe for gastric schwannoma (GS) in the form of case reports. However, study on laparoscopic surgery in patients with GS larger than 30 mm has been rarely reported. To this end, the present study aimed to evaluate the safety and efficacy of laparoscopic resection for the treatment of GS larger than 30 mm and its long-term outcomes., Methods: This is a retrospective case series study of patients with GS larger than 30 mm who underwent laparoscopic resection at our hospital between January 2014 and December 2020. Clinical pathology, surgical and follow-up data were collected and analyzed., Results: A total of 10 patients with a mean age of 51.6 years were included. Seven tumors were located in gastric body, 2 in antrum and 1 in fundus. Laparoscopic gastric wedge resection was performed in 7 patients, while laparoscopic gastric local resection was performed in 3 patients. All patients achieved complete resection. The mean operation time was 112.6 ± 34.3 min, and the mean postoperative hospital stay was 13.8 ± 5.1 days. Postoperative gastroplegia occurred in 2 patients and was treated with conservative therapy. No recurrence, metastasis or residue was found during the follow-up of mean 45.1 months., Conclusions: Laparoscopic resection is a safe and effective method for treating GS larger than 30 mm with favorable long-term follow-up outcomes. Laparoscopic resection may be considered as the first-line treatment for GS larger than 30 mm., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Schistosomiasis japonicum can cause different degrees of organ damage and complex human immune pathological reactions, which often invade the intestine and liver. The purpose of this study was to explore the pathological types and pathological changes of Schistosomiasis and their correlation with some digestive system tumors. Hematoxylin eosin staining was performed on the diseased tissues of 1111 Schistosomiasis cases. We counted the deposition sites of Schistosoma eggs, analyzed the pathological characteristics, and compared the clinicopathological characteristics of Schistosomiasis associated digestive system tumors and non-Schistosomiasis digestive system tumors. We found that Schistosoma japonicum can cause multi organ and multi system damage, with 469 cases of inflammation, 47 cases of adenoma, and 519 cases of adenocarcinoma. Other types include cysts, stromal tumors, malignant lymphomas, and neuroendocrine tumors. Schistosomiasis associated tumors, including gastric cancer, liver cancer, colon cancer and rectal cancer, were compared with non-Schistosomiasis tumors. There were significant differences in age, gender and tumor differentiation between the two groups. Our study shows Schistosomiasis is a systemic disease, causing multiple organ and system damage in the human body. Its clinicopathological types are diverse, and there may be a pathological change process of "Inflammation-adenoma-carcinoma". Schistosomiasis associated digestive system tumors differ from non-Schistosomiasis tumors in some clinicopathological features., (© 2023. Springer Nature Limited.)

Digestive system tumors are huge health problem worldwide, largely attributable to poor dietary choices. The role of RNA modifications in cancer development is an emerging field of research. RNA modifications are associated with the growth and development of various immune cells, which, in turn, regulate the immune response. The majority of RNA modifications are methylation modifications, and the most common type is the N6-methyladenosine (m6A) modification. Here, we reviewed the molecular mechanism of m6A in the immune cells and the role of m6A in the digestive system tumors. However, further studies are required to better understand the role of RNA methylation in human cancers for designing diagnostic and treatment strategies and predicting the prognosis of patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: To elucidate the influence of CXC motif chemokine receptor 4 (CXCR4)-directed imaging on staging and proposed oncologic management in patients with digestive system tumors compared with guideline-appropriate imaging (GAI)., Methods: From our PET/CT database, we retrospectively identified 37 patients with advanced digestive system tumors, which had been scheduled for CXCR4-targeted [ 68 Ga]Ga-pentixafor PET/CT for potential theranostic considerations. In all subjects, concurrent GAI was also available. Patients were afflicted with gastroenteropancreatic neuroendocrine neoplasms (21/37 [56.8%]), pancreatic duct adenocarcinoma (6/37 [16.2%]), cholangiocarcinoma (5/37 [13.5%]), hepatocellular carcinoma (4/37 [10.8%]), and colorectal carcinoma (1/37 [2.7%]). Staging results and impact on proposed oncologic management by a board-certified gastroenterologist were compared between GAI and [ 68 Ga]Ga-pentixafor PET/CT., Results: Relative to GAI, CXCR4-directed PET/CT resulted in staging changes in 14 of 37 patients (37.8%). Upstaging was seen in 1 of 14 patients (7.1%), whereas downstaging was recorded in the remaining 13 of 14 patients (92.9%). Among those, staging changes would not have triggered any changes in oncological management in 4 of 14 (28.6%). For the remaining 10 of 14 patients (71.4%), however, findings on [ 68 Ga]Ga-pentixafor PET/CT would have impacted subsequent clinical algorithm, including the necessity for further diagnostic steps or failure to initiate antitumor therapy., Conclusion: [ 68 Ga]Ga-pentixafor PET/CT missed tumor lesions in 13 patients with digestive system tumors, which would have led to inappropriate downstaging and clinical treatment of 10 patients. As such, our results do not support a more widespread use of [ 68 Ga]Ga-pentixafor PET/CT for clinical staging in those tumor entities., Competing Interests: Conflicts of interest and sources of funding: This project was partially supported by the Okayama University “RECTOR” Program, KAKENHI grant (21K19450) from the Japan Society for the Promotion of Science (to T.H.) and the German Research Foundation (507803309, to R.A.W.; 453989101, to R.A.W., T.H.). R.A.W. and A.K.B. have received speaker's honoraria from PentixaPharm. A.K.B. is a member of the advisory board of PentixaPharm. All other authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Studies have shown that myeloma cell leukemia-1 (MCL-1) is associated with the prognosis of patients with cancer. To further validate the prognostic value of MCL-1 in cancer, a meta-analysis was conducted., Methods: Six databases were searched using Boolean logic search formulas. Data were extracted from the included literature, and pooled odds ratio, hazard ratio, and 95% confidence interval were calculated to determine the relationship between MCL-1 levels and clinicopathological characteristics and prognosis of patients with cancer. When heterogeneity was found to be significant, a random effects model was used, otherwise, a fixed effects model was used., Results: Twelve articles were included in this meta-analysis, totaling 2208 patients with cancer across 14 studies. A high MCL-1 expression level was associated with patients with high T stage, M stage, and TNM stage in some cancers. Additionally, high MCL-1 expression was likely to be observed in patients with poorly differentiated digestive system tumors and patients with lung adenocarcinoma. Notably, a higher expression of MCL-1 was found to be associated with shorter overall survival in patients with hematological tumors, digestive system tumors, and lung cancer., Conclusion: MCL-1 may be a prognostic biomarker in patients with some types of cancer.

Purpose: Claudin 18.2 (CLDN18.2) is a reliable target for lesion detection and could have clinical implications for epithelial tumors, especially digestive system neoplasms. However, there is no predictive technology for accurate whole-body mapping of CLDN18.2 expression in patients. This study assessed the safety of the 124 I-18B10(10L) tracer and the feasibility of mapping whole-body CLDN18.2 expression using PET functional imaging., Methods: The 124 I-18B10(10L) probe was synthesized manually, and preclinical experiments including binding affinity and specific targeting ability were conducted after testing in vitro model cells. Patients with pathologically confirmed digestive system neoplasms were enrolled in an ongoing, open-label, single-arm, first-in-human (FiH) phase 0 trial (NCT04883970). 124 I-18B10(10L) PET/CT or PET/MR and 18 F-FDG PET were performed within one week., Results: 124 I-18B10(10L) was successfully constructed with an over 95% radiochemical yield. The results of preclinical experiments showed that it had high stability in saline and high affinity in CLDN18.2 overexpressing cells (Kd = 4.11 nM). Seventeen patients, including 12 with gastric cancers, 4 with pancreatic cancers, and 1 with cholangiocarcinoma were enrolled. 124 I-18B10(10L) displayed high uptake in the spleen and liver, and slight uptake in the bone marrow, lung, stomach and pancreas. The tracer uptake SUV max in tumor lesions ranged from 0.4 to 19.5. Compared with that in lesions that had been treated with CLDN18.2-targeted therapy, 124 I-18B10(10L) uptake was significantly higher in lesions that had not. Regional 124 I-18B10(10L) PET/MR in two patients showed high tracer uptake in metastatic lymph nodes., Conclusions: 124 I-18B10(10L) was successfully prepared and exhibited a high binding affinity and CLDN18.2 specificity in preclinical studies. As an FiH CLDN18.2 PET tracer, 124 I-18B10(10L) was shown to be safe with acceptable dosimetry and to clearly reveal most lesions overexpressing CLDN18.2., Trial Registration: NCT04883970; URL: https://register., Clinicaltrials: gov/ . Registered 07 May 2021., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: There is scant evidence regarding the effects of exercise type and duration on quality of life (QoL) in digestive system cancer (DSC) survivors. We aim to investigate the optimal type and duration of exercise to improve QoL for DSC survivors through a systematic review and network meta-analysis., Methods: A systematic literature search of PubMed, Embase, and Web of Science was performed. Eligibility for study inclusion was limited to studies that were randomized controlled trials involving all kinds of exercise in adult patients with DSCs, and the comparator was in standard care or other types of exercise. The primary outcome was QoL, including general health, physical health, mental health, and role function. Secondary outcomes included cancer-related symptoms such as fatigue, insomnia, depression, anxiety, and duration of hospital stay. The network meta-analyses were performed using a random-effect model., Results: The analysis included 32 eligible articles and a total of 2558 participants. Our primary outcome indicated that short-term aerobic exercise significantly enhanced general health (standardized mean difference (SMD) = 0.66, 95% credible intervals (CrIs): 0.05 to 1.30), and also contributed to a better mental health (SMD = 0.38, 95%CrI: -0.05 to 0.81) and role function (SMD = 0.48, 95%CrI: -0.27 to 1.20). Although without significant changes, short-term resistance exercise tended to increase the physical health of patients with DSCs (SMD = 0.69, 95%CrI: -0.07 to 1.50) and effective in alleviating fatigue (SMD = -0.77, 95%CrI: -1.50 to 0.01). Short-term aerobic exercise was related to a lower score of insomnia (SMD = -1.20, 95%CrI: -2.40 to 0.06), depression (SMD = -0.51, 95%CrI: -1.50 to 0.45), and anxiety (SMD = -0.45, 95%CrI: -1.30 to 0.34). All types of exercise related to a trend of declined hospital stays (-0.87 to -5.00 day). Long-term resistance exercise, however, was negatively associated with general health (SMD = -0.33, 95%CrI: -1.70 to 1.00), physical health (SMD = -0.18, 95%CrI: -1.30 to 0.90), and role function (SMD = -1.20, 95%CrI: -2.50 to 0.11)., Conclusion: This study suggests that short-term aerobic exercise, with or without resistance exercise programs, enhances QoL (especially for general health) as well as relieves cancer-related symptoms for DSC survivors, while long-term resistance exercise may have negative effects, and thus should be adopted cautiously. These results provide important evidence for the management of DSCs., (Copyright © 2023. Production and hosting by Elsevier B.V.)

While gastrointestinal tumors remain a multifactorial and prevalent group of malignancies commonly treated surgically in combination with chemotherapy and radiotherapy, advancements regarding immunotherapeutic approaches continue to occur. Entering a new era of immunotherapy focused on overcoming resistance to preceding therapies caused the emergence of new therapeutic strategies. A promising solution surfaces with a V-domain Ig suppressor of T-cell activation (VISTA), a negative regulator of a T-cell function expressed in hematopoietic cells. Due to VISTA's ability to act as both a ligand and a receptor, several therapeutic approaches can be potentially developed. A broad expression of VISTA was discovered on various tumor-growth-controlling cells, which proved to increase in specific tumor microenvironment (TME) conditions, thus serving as a rationale behind the development of new VISTA-targeting. Nevertheless, VISTA's ligands and signaling pathways are still not fully understood. The uncertain results of clinical trials suggest the need for future examining inhibitor agents for VISTA and implicating a double immunotherapeutic blockade. However, more research is needed before the breakthrough can be achieved. This review discusses perspectives and novel approaches presented in the current literature. Based on the results of the ongoing studies, VISTA might be considered a potential target in combined therapy, especially for treating gastrointestinal malignancies.

Introduction: Due to longer life expectancy, an increasing number of older people are at risk of developing cancer. Surgical resection of a non-metastatic and resectable digestive tumor remains the main therapeutic weapon. The objective of our study is to assess the possibility of curative oncological surgery in patients over 80years of age, to study its impact in terms of morbidity and mortality, and to look for risk factors for the occurrence of complications., Patients and Methods: The study-included patients aged 80 and over operated on for digestive cancer in a curative situation. This was a multicenter prospective cohort study. A total of 230 patients were included in the study. In addition to demographic and medical data, the patients all benefited from an onco-geriatric assessment with the performance of various tests: WHO score, G8 score, IADL score, ADL score, mobility score, nutritional assessment, clock, thymic evaluation (Mini-GDS). Data collection of geriatric scores was repeated 3months postoperatively., Results: Of a total of 230 patients, 51% were male and 49% female. The average age was 84.7years. Tumor localization was mainly colorectal (65.81%). Age had no influence on the mortality rate, with a mean age with no significant difference in the event of an unfavorable outcome or not (84.6 vs. 85years). The results at the different scores were then analyzed in search of a significant difference between preoperative and at 3months. The only significant difference found was in the number of patients with a WHO status of 0 (P=0.021)., Conclusion: Our study shows that curative oncological surgery is possible in elderly patients without any adverse effect on their quality of life and level of postoperative autonomy. The multidisciplinary geriatric approach to the patient must make it possible to distinguish the patients who will benefit from a curative treatment and those in whom the benefit-risk balance is unfavorable., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

We introduce the case of a 40-year-old male with no medical history of interest who was admitted in the Digestive System unit due to upper gastrointestinal bleeding, and a large protruding lesion located in gastric antrum was detected during oral endoscopy, but biopsies were negative for malignancy. Therefore, endoscopic ultrasound was performed, confirming the submucosal origin of the lesion, puncturing it, and obtaining histological results compatible with leiomyoma. Gastric leiomyomas are rare mesenchymal tumors that are usually asymptomatic and are detected by performing a procedure for another reason. The definitive diagnosis is histological, being sometimes difficult to obtain samples given the submucosal origin of these lesions. The main treatment is surgery, although endoscopic resection is accepted in certain cases.

Background: An association between inflammatory bowel disease (IBD) and pancreatic cancer has been suggested in the literature. We aimed to determine the trend in prevalence of pancreatic cancer amongst patients hospitalized for Crohn's disease (CD) or ulcerative colitis (UC) in the United States., Methods: An analysis of the National Inpatient Sample database was performed to identify adults diagnosed with pancreatic cancer and CD or UC, using validated ICD-9 and ICD-10 codes, from 2003-2017. Age, sex, and racial demographics were also collected. Surveillance, Epidemiology and End Results registry (SEER) data were analyzed for trends in the incidence and mortality of pancreatic cancer amongst the general population in the United States., Results: From 2003-2017, there was a significant increase in the hospitalizations related to pancreatic cancer, from 0.11% to 0.19% (P Trend <0.001), representing a 72.73% increase, in CD patients, and from 0.08% to 0.38% (P Trend <0.001), representing a 375.00% increase, in UC patients. According to the SEER 13 data on pancreatic cancer in the general population, the incidence of pancreatic cancer increased from 11.34 per 100,000 cases in 2003 to 12.74 per 100,000 cases in 2017, thus representing only a 12.35% increase over the study period., Conclusions: Our study indicates a trend for increasing prevalence of pancreatic cancer in patients hospitalized with CD and UC from 2003-2017 in the United States. This increasing trend observed in the IBD population parallels the increase in the incidence of pancreatic cancer reported among the general population, but at a much greater rate., Competing Interests: Conflict of Interest: None, (Copyright: © Hellenic Society of Gastroenterology.)

Objective: To differentiate gastric leiomyomas (GLs) and gastric stromal tumors (GSTs) based on preoperative enhanced computed tomography characteristics., Methods: Twenty-six pathologically confirmed GLs were propensity score-matched to 26 GSTs in a 1:1 ratio based on sex, age, tumor site, and tumor size. Tumor shape and contour, mucosal ulceration, growth pattern, enhancement pattern and degree, longest diameter, and longest diameter/vertical diameter ratio were compared between the groups. Hemorrhage, calcification, peripheral invasion, and distant metastasis were also included in the regression analysis for differentiation of the two tumors., Results: Mucosal ulceration was significantly more frequent in GSTs than GLs. The enhancement degree of GSTs was significantly higher than that of GLs in the arterial and portal venous phases. Using enhancement degrees of 18 HU and 23 HU in the arterial phase and venous phase as cutoff values, respectively, we found that an enhancement degree of <18 HU in the arterial phase was an independent influential factor for diagnosis of GLs. No significant differences were found in other morphological characteristics. GLs did not metastasize or invade adjacent tissues., Conclusion: A low enhancement degree in GLs is the most valuable quantitative feature for differentiating these two similar tumors.

We present and discuss the case of one patient that presented to the emergency room with abdominal pain in the right hypochondrium radiated to epigastrium and low-grade fever with blood test that shows dissociated colesthasis therefore admitted in the gastroenterology service with choledocholithiasis suspicion. cholangioresonance performed with a sudden stenosis of the bile duct in its intrapancreatic portion due a tumor in the pancreatic head. CT without lessions in other parts of the body. Upper endoscopy shows an ulcerated growth in the papillary area whose biopsies found neoplastic proliferation with S100, SOX10, MelanA and HMB45 positivity.

Introduction: Prophylactic total gastrectomy (PTG) can eliminate gastric cancer risk and is recommended in carriers of a germline CDH1 pathogenic variant. PTG has established risks and potential life-long morbidity. Decision-making regarding PTG is complex and not well-understood., Methods: Individuals with germline CDH1 pathogenic or likely pathogenic variants who underwent surveillance endoscopy and recommended for PTG were evaluated. Factors associated with decision to pursue PTG (PTG pos ) or not (PTG neg ) were queried. A decision-regret survey was administered to patients who elected PTG., Results: Decision-making was assessed in 120 patients. PTG pos patients (63%, 76/120) were younger than PTG neg (median 45 vs 58 years) and more often had a strong family history of gastric cancer (80.3% vs 34.1%). PTG pos patients reported decision-making based on family history more often and decided soon after diagnosis (8 vs 27 months) compared with PTG neg . Negative endoscopic surveillance results were more common among PTG neg patients. Age >60 years, male sex and longer time to decision were associated with deferring PTG. Strong family history, a family member who died of gastric cancer and carcinoma on endoscopic biopsies were associated with decision to pursue PTG. In the PTG pos group, 30 patients (43%) reported regret which was associated with occurrence of a postoperative complication and no carcinoma detected on final pathology., Conclusion: The decision to undergo PTG is influenced by family cancer history and surveillance endoscopy results. Regret is associated with surgical complications and pathological absence of cancer. Individual cancer-risk assessment is necessary to improve pre-operative counselling and inform the decision-making process., Trial Registration Number: NCT03030404., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on cancer diagnosis and care pathways. Here, we assessed the mid-term impact of the COVID-19 pandemic on older adults with cancer before, during and after the lockdown period in 2020., Materials and Methods: We performed a retrospective, observational, multicentre cohort study of prospectively collected electronic health records. All adults aged 65 or over and having been newly treated for a digestive system cancer in our institution between January 2018 until August 2020 were enrolled., Results: Data on 7,881 patients were analyzed. Although the overall 10-month mortality rate was similar in 2020 vs. 2018-2019, the mortality rate among for patients newly treated in the 2020 post-lockdown period was (after four months of follow-up) significantly higher. A subgroup analysis revealed higher mortality rates for (i) patients diagnosed in the emergency department during the pre-lockdown period, (ii) patients with small intestine cancer newly treated during the post-lockdown period, and (iii) patients having undergone surgery with curative intent during the post-lockdown period. However, when considering individuals newly treated during the lockdown period, we observed lower mortality rates for (i) patients aged 80 and over, (ii) patients with a biliary or pancreatic cancer, and (iii) patients diagnosed in the emergency department., Discussion: There was no overall increase in mortality among patients newly treated in 2020 vs. 2018-2019. Longer follow-up is needed to assess the consequences of the pandemic. A subgroup analysis revealed significant intergroup differences in mortality., Competing Interests: Declaration of Competing Interest All authors declare no conflicts of interest with regard to this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Immunotherapy has remained at the vanguard of promising cancer therapeutic regimens due to its exceptionally high specificity for tumor cells and potential for significantly improved treatment-associated quality of life compared to other therapeutic approaches such as surgery and chemoradiation. This is especially true in the digestive system, where high rates of mutation give rise to a host of targetable tumor-specific antigens. Many patients, however, do not exhibit measurable improvements under immunotherapy due to intrinsic or acquired resistance, making predictive biomarkers necessary to determine which patients will benefit from this line of treatment. Many of these biomarkers are assessed empirically by pathologists according to nuanced scoring criteria and algorithms. This review serves to inform clinicians and pathologists of extant and promising upcoming biomarkers predictive of immunotherapeutic efficacy among digestive system malignancies and the ancillary testing required for interpretation by pathologists according to tumor site of origin.

Objective: IKBKB-interacting protein (IKBIP) has rarely been reported in tumor research. This study aimed to evaluate IKBIP role in tumor progression. mRNA (messenger ribonucleic acid) expression, clinical characteristics and predictive values of IKBIP were assessed., Methods: R package "clusterProfiler" was used to examine the potential mechanisms in which IKBIP may involve. Immune cell infiltration and its correlation with IKBIP was also analyzed. We further evaluated IKBIP influence on drug resistance., Results: It was found that IKBIP was overexpressed and related to poorer survival in most types of tumors. IKBIP expression was strongly related to immunosuppressive cells in the TCGA (The Cancer Genome Atlas) pan-cancer samples. These immunosuppressive cells included tumor-related macrophages, tumor-related fibroblasts, and regulatory T cells. Moreover, immunosuppressive genes and immune checkpoints were positively related to IKBIP expression in several tumor types. Furthermore, patients with IKBIP overexpressed did not respond to most anti-cancer medications. It was also found that compared to control group, the number of invasive cells is four times that of IKBIP overexpression group, and the number of clone forming cells is six times that of IKBIP overexpression group. IKBIP overexpression promoted colon cancer cells invasiveness and clonogenesis by Transwell assay and colon formation assay., Conclusions: According to current findings, IKBIP is a probable oncogene and predictive marker for most of tumor types. High IKBIP expression is associated with tumor immunosuppression.

OBJECTIVE: Malnutrition-related disease particularly occur in patients with digestive system cancer. The administration of oral nutritional supplements (ONSs) is one of the methods of nutritional support recommended for oncological patients. The primary aim of this study was to assess the consumption-related aspects of ONSs among patients with digestive system cancer. The secondary aim was to assess the impact of ONSs consumption on the quality of life of these patients. PATIENTS AND METHODS: The current study included 69 patients with digestive system cancer. The assessment of ONSs-related aspects among cancer patients was conducted using a self-designed questionnaire, which has been accepted by Independent Bioethics Committee. RESULTS: Among all patients, 65% of participants declared that they consumed ONSs. Patients consumed various types of ONSs. However, the most common were protein products (40%) and standard products (37.78%). Only 4.44% of patients consumed products with immunomodulatory ingredients. Nausea was the most commonly (15.56%) observed side effect after ONSs consumption. Considering particular types of ONSs, side effects were the most commonly declared by patients who consumed standard products (p=0.157). The easy product availability in the pharmacy was noted by 80% of participants. However, 48.89% of patients assessed the cost of ONSs as not acceptable (48.89%). 46.67% of studied patients did not observe the improvement of quality of life after ONSs consumption. CONCLUSIONS: We have demonstrated that patients with digestive system cancer consumed various period, amount, and types of ONSs. Side effects after ONSs consumption occur rarely. However, the improvement of quality of life related to ONSs consumption was not noted in almost half of participants. ONSs are easily available in pharmacy.

Objective: To investigate the clinical features of patients with cardiac metastases from digestive system tumors. Methods: This retrospective study collected and analyzed the medical records of patients with cardiac metastases from digestive system tumors who received treatments in the Cancer Hospital, Chinese Academy of Medical Sciences between January 1999 and January 2021. Kaplan-Meier method was used for survival analysis. Results: A total of 19 patients were identified. The primary tumors were esophageal squamous cell carcinoma ( n =7), gastric or gastroesophageal junction adenocarcinoma ( n =6), hepatobiliary cancers ( n =3) and colorectal cancers ( n =3). 16 patients had pericardial metastases, 2 patients had right atrium metastases, and 1 patient had left ventricle metastasis. The most common symptom was dyspnea, which was present in 8 cases. 7 patients received locoregional treatment, while 11 patients underwent systemic therapies. The median overall survival from diagnosis of primary cancer was 31.4 months, and the median overall survival time from diagnosis of cardiac metastasis was 4.7 months. Conclusion: Cardiac metastasis from digestive system tumors is associated with low incidence and a poor prognosis. Systemic treatment remains the cornerstone of management, while novel anti-tumor drugs may improve therapeutic efficacy.

Background: It has been previously reported that CD155 is often over-expressed in a variety of cancer types. In fact, it is known to be involved in cancer development, and its role in cancer has been widely established. However, clinical and mechanistic studies involving CD155 yielded conflicting results. Thus, the present study aimed to evaluate overall prognostic value of CD155 in cancer patients, using a comprehensive analysis., Methods: Online databases were searched, data was collected, and clinical value of CD155 was evaluated by combining hazard ratios (HRs) or odds ratios (ORs)., Results: The present study involved meta-analysis of 26 previous studies that involved 4325 cancer patients. These studies were obtained from 25 research articles. The results of the study revealed that increased CD155 expression was significantly associated with reduced OS in patients with cancer as compared to low CD155 expression (pooled HR = 1.772, 95% CI = 1.441-2.178, P < 0.001). Furthermore, subgroup analysis demonstrated that the level of CD155 expression was significantly associated with OS in patients with digestive system cancer (pooled HR = 1.570, 95% CI = 1.120-2.201, P = 0.009), hepatobiliary pancreatic cancer (pooled HR = 1.677, 95% CI = 1.037-2.712, P = 0.035), digestive tract cancer (pooled HR = 1.512, 95% CI = 1.016-2.250, P = 0.042), breast cancer (pooled HR = 2.137, 95% CI = 1.448-3.154, P < 0.001), lung cancer (pooled HR = 1.706, 95% CI = 1.193-2.440, P = 0.003), head and neck cancer (pooled HR = 1.470, 95% CI = 1.160-1.862, P = 0.001). Additionally, a significant correlation was observed between enhanced CD155 expression and advanced tumor stage (pooled OR = 1.697, 95% CI = 1.217-2.366, P = 0.002), LN metastasis (pooled OR = 1.953, 95% CI = 1.253-3.046, P = 0.003), and distant metastasis (pooled OR = 2.253, 95% CI = 1.235-4.110, P = 0.008)., Conclusion: Altogether, the results of the present study revealed that CD155 acted as an independent marker of prognosis in cancer patients, and it could provide a new and strong direction for cancer treatment., (© 2022. The Author(s).)

In the FIGHTDIGO study, digestive cancer patients with dynapenia experienced more chemotherapy-induced neurotoxicities. FIGHTDIGOTOX aimed to evaluate the relationship between pre-therapeutic handgrip strength (HGS) and chemotherapy-induced dose-limiting toxicity (DLT) or all-grade toxicity in digestive cancer patients. HGS measurement was performed with a Jamar dynamometer. Dynapenia was defined according to EWGSOP2 criteria (<27 kg (men); <16 kg (women)). DLT was defined as any toxicity leading to dose reduction, treatment delay, or permanent discontinuation. We also performed an exploratory analysis in patients below the included population’s median HGS. A total of 244 patients were included. According to EWGSOP2 criteria, 23 patients had pre-therapeutic dynapenia (9.4%). With our exploratory median-based threshold (34 kg for men; 22 kg for women), 107 patients were dynapenic (43.8%). For each threshold, dynapenia was not an independent predictive factor of overall DLT and neurotoxicity. Dynapenic patients according to EWGSOP2 definition experienced more hand-foot syndrome (p = 0.007). Low HGS according to our exploratory threshold was associated with more all-grade asthenia (p = 0.014), anemia (p = 0.006), and asthenia with DLT (p = 0.029). Pre-therapeutic dynapenia was not a predictive factor for overall DLT and neurotoxicity in digestive cancer patients but could be a predictive factor of chemotherapy-induced anemia and asthenia. There is a need to better define the threshold of dynapenia in cancer patients.

Digestive system cancer is the most common cause of cancer death in the world. Although cancer treatment options are increasingly diversified, the mortality rate of malignant cancer of the digestive system remains high. Therefore, it is necessary to explore effective cancer treatment methods. Recently, biomimetic nanoparticle delivery systems based on natural cells that organically integrate the low immunogenicity, high biocompatibility, cancer targeting, and controllable, versatile functionality of smart nanocarrier design with natural cells have been expected to break through the bottleneck of tumor targeted therapy. In this review, we focus on the dynamic changes and complex cellular communications that occur in vivo in natural cells based vehicles. Recent studies on the development of advanced targeted drug delivery systems using the dynamic behaviors such as specific surface protein affinity, morphological changes, and phenotypic polarization of natural cells are summarized. In addition to drug delivery mediated by dynamic behavior, functional "delivery" based on the natural cell themselves is also involved. Aiming to make the best use of the functions of cells, providing clues for the development of advanced drug delivery platforms., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background & Aims: In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease., Methods: We leveraged longitudinal data from 3 prospective cohorts, the Nurses' Health Study (1984-2018, 73,166 women aged 65.1 ± 10.8 years), Nurses' Health Study II (1991-2017, 90,423 women aged 49.1 ± 8.2 years), and Health Professionals Follow-Up Study (1986-2016, 42,617 men aged 64.8 ± 10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios and 95% confidence intervals of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires., Results: During 4,801,513 person-years of follow-up, we documented 6231 incident digestive system cancer cases among 3 cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a hazard ratio of 0.94 (95% confidence interval, 0.87-1.02) comparing the highest with the lowest quintile of gluten intake (P trend = .05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer., Conclusions: Gluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate the clinical features, diagnostic criteria, treatment options, and prognosis of patients with gastric schwannoma (GS)., Methods: We collected the clinical data of all patients pathologically diagnosed with GS in Zhejiang Provincial People's Hospital from May 2012 to October 2021., Results: A total of 26 cases of GS were analyzed clinicopathologically, where the sizes of the tumor were found to be in the range of 1-6 cm (mean: 3.16 cm, median: 3.05 cm). A computed tomography (CT) scan analysis revealed that most masses were either moderately progressive or uniformly enhanced. According to ultrasound gastroscopy results, most of them were hypoechoic masses. There were 23 cases of surgery and three cases of endoscopic submucosal tumor dissection. Immunohistochemistry demonstrated that S100 was positive in 26 patients, immunomarker SOX10 was positive in five, whereas CD34, CD117, and SMA were negative in most patients. CK (Pan), Dog-1, and Desmin were also found negative. All 26 cases were followed up after the conclusion of the study where no evidence of recurrence or metastasis was observed., Conclusions: GS is a unique form of peripheral schwannoma. The diagnosis of this type of tumor depends on the pathology and immunohistochemistry of the individual. The key to treating this type of tumor is endoscopy and surgery. Follow up and related literature review showed that GS was a benign tumor with little possibility of malignant transformation., (© 2022. The Author(s).)

Background: Cancer, like other chronic pathologies, is associated with the presence of hypoxic regions due to the uncontrolled cell growth. Under this pathological hypoxic condition, various molecular signaling pathways are activated to ensure cell survival, such as those that govern angiogenesis, erythropoiesis, among others. These molecular processes are very similar to the physiological response caused by exposure to altitude (natural hypobaric systemic hypoxia), the use of artificial hypoxia devices (systemic normobaric simulated hypoxia) or the delivery of vascular occlusion to the extremities (also called local hypoxia by the blood flow restriction technique). "Tumor hypoxia" has gained further clinical importance due to its crucial role in both tumor progression and resistance to treatment. However, the ability to manipulate this pathway through physical exercise and systemic hypoxia-mediated signaling pathways could offer an important range of therapeutic opportunities that should be further investigated., Methods: This review is focused on the potential implications of systemic hypoxia combined with exercise in digestive system neoplasms prognosis. Articles included in the review were retrieved by searching among the three main scientific databases: PubMed, Scopus, and Embase., Findings: The findings of this review suggest that exercise performed under systemic hypoxic conditions could have a positive impact in prognosis and quality of life of the population with digestive system cancers., Conclusions: Further studies are needed to consider this paradigm as a new potential intervention in digestive oncological population., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Plexiform fibromyxoma (PFM) is a rare gastrointestinal tract tumor that develops in the stomach in most cases. Here, we report an extremely rare case of esophageal PFM. A female in her mid-30 s presented with difficulty in swallowing and breathing. Endoscopic examination revealed a submucosal tumor measuring approximately 45 × 50 mm in the upper thoracic esophagus. The biopsied specimen did not show definite histological evidence of gastrointestinal stromal tumors (GISTs). Since imatinib administration based on a clinical diagnosis of GIST did not show a therapeutic effect for tumor reduction, tumor resection was performed. The resected tumor exhibited proliferation of spindle tumor cells with abundant myxoid and vascular stroma separated by a muscular layer, indicating a plexiform arrangement. Immunohistochemical analysis demonstrated that the tumor cells diffusely expressed vimentin and alpha-smooth muscle actin, but not desmin, c-kit, DOG1, and CD34. MALAT1-GLI1 fusion was detected in formalin-fixed paraffin-embedded tissue using RT-PCR and Sanger sequencing. The results suggested that a fibromyxoid tumor can develop in the esophagus, showing an identical histology and MALAT1-GLI1 fusion to gastric PFM., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Purpose: Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of osteopenia in digestive tract cancers remains to be defined. We aimed to review the prognostic value of preoperative osteopenia in patients with digestive cancers., Methods: Cohort studies evaluating the prognostic value of preoperative osteopenia in digestive cancers (colorectal, esophageal, hepatic, bile duct, and pancreatic cancer) were searched using electronic databases and trial registries. The exposure was defined as low BMD estimated by computed tomography at 11 th thoracic vertebra, while comparator was normal BMD. The primary outcomes were overall survival and recurrence-free survival for osteopenia. Random effect meta-analyses were performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence., Results: A total of 11 studies (2230 patients) were included. Osteopenia was an independent risk factor for overall survival (hazard ratio [HR] = 2.02, 95% CI = 1.47 to 2.78; I 2 = 74%), along with sarcopenia. Osteopenia also predicted poor recurrence-free survival (HR = 1.96, 95% CI = 1.36 to 2.81; I 2 = 85%). In subgroup analyses, osteopenia predicted prognosis in colorectal, esophageal, hepatic, and bile duct cancers, but not in pancreatic cancer. The certainty of the evidence was low due to inconsistency and publication bias., Conclusion: Osteopenia may be independently associated with poor prognosis in patients with digestive tract cancer. Further studies are needed to establish the relevance of osteopenia in the operative prognosis of these patients., (© 2022. The Author(s).)

A 52-year-old male patient presented to the Emergency Room due to melena. A gastroscopy was performed, which revealed a submucosal lesion in the antrum of the stomach. The lesion was lined with regular smooth mucosa except for an apical ulceration. Histology showed gastric mucosa with foveolar hyperplasia. Abdominal computed tomography (CT) showed a homogeneous, well-delimited fat-density mass measuring 5.9 x 4.3 cm. Laparoscopic surgery then found a solid tumor involving the whole thickness of the anterior wall at the prepyloric area, which was resected. Microscopic examination revealed a homogeneous, soft, ulcerated submucosal mass of yellowish adipose tissue that was 5 x 5 x 2 cm in size. Microscopically, the tumor was composed of mature fatty tissue with fibrous septa, and was partially encapsulated and circumscribed. It was reported as a submucosal lipoma. The patient had a favorable outcome.