Autophagy-related ncRNAs: Regulatory Roles and Potential Therapeutic Effects in Digestive System Neoplasms.

Among all cancers in the world, the incidence rate of digestive system neoplasms accounts for about 25%, while the mortality rate accounts for about 35%. Difficulty in detecting early digestive system cancers and its poor prognosis are the two main reasons for the high mortality rate. Understanding of the basic cellular processes is of significance and autophagy is one of these processes. Considering the importance of autophagy in pathological state functions, the mechanism of autophagy was initially carried out. In this paper, we will review the molecular mechanisms and biological functions of autophagy-associated ncRNAs in different types of digestive system cancers. Autophagy is a process that supports nutrient cycling and metabolic adaptation accomplished through multi-step lysosomal degradation. It has been suggested that autophagy has a dual role in cancer, which limits tumorigenesis in some stages but promotes tumor progression in others. NcRNAs are also shown to modulate cellular autophagy and thus affect the development of digestive system neoplasms. More and more evidence suggests that the regulation of autophagy by ncRNAs plays a complex role in cancer initiation, progression, metastasis, recurrence, and treatment resistance, which might make ncRNAs therapeutic targets for digestive system neoplasms. While miRNAs participate mainly in post-transcriptional regulation, lncRNAs, and circRNAs usually serve as molecular sponges that have more diverse regulatory functions.

The role of SWI/SNF complexes in digestive system neoplasms.

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.

Mechanisms of Anti-PD Therapy Resistance in Digestive System Neoplasms.

Digestive system neoplasms are highly heterogeneous and exhibit complex resistance mechanisms that render anti-programmed cell death protein (PD) therapies poorly effective. The tumor microenvironment (TME) plays a pivotal role in tumor development, apart from supplying energy for tumor proliferation and impeding the body's anti-tumor immune response, the TME actively facilitates tumor progression and immune escape via diverse pathways, which include the modulation of heritable gene expression alterations and the intricate interplay with the gut microbiota. In this review, we aim to elucidate the mechanisms underlying drug resistance in digestive tumors, focusing on immune-mediated resistance, microbial crosstalk, metabolism, and epigenetics. We will highlight the unique characteristics of each digestive tumor and emphasize the significance of the tumor immune microenvironment (TIME). Furthermore, we will discuss the current therapeutic strategies that hold promise for combination with cancer immune normalization therapies. This review aims to provide a thorough understanding of the resistance mechanisms in digestive tumors and offer insights into potential therapeutic interventions.

Knee Extensor Weakness Potently Predicts Postoperative Outcomes in Older Gastrointestinal Cancer Patients.

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.

Development of a Novel Comprehensive Hepatocellular Carcinoma Outcome Prognostic Scoring System With Integration of Imaging Features.

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.

Exosomes: Another intercellular lipometabolic communication mediators in digestive system neoplasms?

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.

Ability of a polygenic risk score to refine colorectal cancer risk in Lynch syndrome.

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.

Trends in inflammatory bowel disease and pancreatic cancer: an analysis of the National Inpatient Sample database.

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% (PTrend<0.001), representing a 72.73% increase, in CD patients, and from 0.08% to 0.38% (PTrend<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.

First-in-human CLDN18.2 functional diagnostic pet imaging of digestive system neoplasms enables whole-body target mapping and lesion detection.

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 124I-18B10(10L) tracer and the feasibility of mapping whole-body CLDN18.2 expression using PET functional imaging. METHODS: The 124I-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). 124I-18B10(10L) PET/CT or PET/MR and 18F-FDG PET were performed within one week. RESULTS: 124I-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. 124I-18B10(10L) displayed high uptake in the spleen and liver, and slight uptake in the bone marrow, lung, stomach and pancreas. The tracer uptake SUVmax in tumor lesions ranged from 0.4 to 19.5. Compared with that in lesions that had been treated with CLDN18.2-targeted therapy, 124I-18B10(10L) uptake was significantly higher in lesions that had not. Regional 124I-18B10(10L) PET/MR in two patients showed high tracer uptake in metastatic lymph nodes. CONCLUSIONS: 124I-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, 124I-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.

Position statement of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) on APC I1307K and cancer risk.

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.

Decision-making and regret in patients with germline CDH1 variants undergoing prophylactic total gastrectomy.

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 (PTGpos) or not (PTGneg) were queried. A decision-regret survey was administered to patients who elected PTG. RESULTS: Decision-making was assessed in 120 patients. PTGpos patients (63%, 76/120) were younger than PTGneg (median 45 vs 58 years) and more often had a strong family history of gastric cancer (80.3% vs 34.1%). PTGpos patients reported decision-making based on family history more often and decided soon after diagnosis (8 vs 27 months) compared with PTGneg. Negative endoscopic surveillance results were more common among PTGneg 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 PTGpos 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.

Effect of spontaneous breathing on atelectasis during induction of general anesthesia in patients undergoing laparoscopic resection of gastrointestinal tumors / 肿瘤研究与临床

Objective:To explore the effect of spontaneous breathing during induction of general anesthesia on atelectasis in patients undergoing laparoscopic resection of gastrointestinal tumors.Methods:A total of 60 patients aged 18-60 years scheduled for laparoscopic resection of gastrointestinal tumors under general anesthesia in the First Hospital of Shanxi Medical University from October 2021 to August 2022 were selected. The body mass index was 18.5-28.0 kg/m 2 and the American Society of Anesthesiology grade wasⅠ-Ⅱ. All patients were divided into the spontaneous breathing group (group S, 30 cases) and the controlled breathing group (group C, 30 cases) according to the random number table method. Patients in group S received 0.2-0.3 mg/kg etomidate (pumping at the speed of 200 ml/h) and 2 μg/kg remifentanil (slowly injected more than 30 s) for anesthesia induction; patients in group C received 0.2-0.3 mg/kg etomidate and 2 μg/kg remifentanil (slowly injected more than 30 s) and 0.2 mg/kg cisatracurium. After bispectral index (BIS) decreased to 80, the patients had no response to the language stimulation; and then the mask was used to closely fit the face and maintain spontaneous breathing in group S; patients in group C received manual positive pressure ventilation. Atelectasis scores were collected immediately after endotracheal intubation (T 1) and 15 min after transferring to the recovery room (T 3), and oxygenation index (OI) was collected 5 min after endotracheal intubation (T 2) and at T 3. The postoperative pulmonary complication (PPC) on the 3rd day after the operation was recorded. Results:A total of 56 patients were finally enrolled, 27 cases in group S and 29 cases in groups C. Compared with group C, the atelectasis score of group S at T 1 and T 3 decreased [T 1: (2.4±0.8) scores vs. (4.2±0.7) scores, t = -9.12, P < 0.001; T 3: (8.2±1.8) scores vs. (10.5±1.6) scores, t = -4.96, P < 0.001]. The OI increased at T 2 and T 3 in group S [T 2: (334±11) mmHg (1 mmHg = 0.133 kPa) vs. (323±13) mmHg, t = 3.45, P = 0.001; T 3: (362±23) mmHg vs. (347±25) mmHg, t = 2.31, P = 0.025]. The incidence of PPC was 20.7% (6/29) and 18.5% (5/27), respectively in group C and group S on the 3rd day after the operation, and the difference was statistically significant ( χ2 = 0.04, P = 0.838). Conclusions:Maintaining spontaneous breathing during induction of general anesthesia can reduce atelectasis caused by general anesthesia and improve oxygenation for patients undergoing laparoscopic resection of gastrointestinal tumors.

Efficacy and safety of submucosal tunneling endoscopic resection for multiple submucosal tumors of upper gastrointestinal tract / 中华消化内镜杂志

In order to evaluate the efficacy and safety of submucosal tunneling endoscopic resection (STER) for the treatment of multiple submucosal tumors (SMT) in the upper gastrointestinal tract, data of 24 cases with upper gastrointestinal SMT (including 56 SMT lesions) treated at Taizhou Municipal Hospital and Shanghai East Hospital from January 2016 to June 2021 were collected for retrospective observation. The treatment effect, occurrence of major adverse events and follow-up results were analyzed. The results showed that 19 cases (79.2%) underwent tumor resection through one tunnel, and 5 cases (20.8%) underwent tumor resection through two tunnels. The length of the tunnel was 3-12 cm, with an average of 6.2 cm. The surgical time ranged from 19 to 130 minutes, with an average of 55.6 minutes. The overall resection rate was 89.29% (50/56). The hospitalization time was 2-7 days, with an average of 3.5 days. Major adverse events occurred in 2 cases (8.3%), all of which were mucosal injuries, and were cured with titanium clips and self expanding metal sealing stents. During a follow-up period of 6-64 months, with an average of 32.0 months, there was no residual tumor, tumor implantation tunnel, local recurrence, distant metastasis or death. To sum up, STER is safe and feasible for the treatment of multiple SMT in the upper gastrointestinal tract. The main resection method is single tunnel, and double tunnel is required for multiple SMT far apart.

Applications of artificial intelligence in major gastrointestinal diseases in elderly patients / 中华老年医学杂志

Gastrointestinal tumors(GT)are characterized by both high malignancy and high mortality and have become the major diseases for prevention in the elderly.GT often present detectable changes, including bleeding and abnormal mucosal morphology.However, many technical difficulties remain in accurately monitoring the tumor itself and related abnormal lesions mentioned above, which are the key factors affecting the early detection rate of gastrointestinal tumors.In recent years, with progresses in artificial intelligence(AI)applications for digestive endoscopy image analysis, biosensors, new biomarkers and other areas, AI holds promise for the detection of bleeding, morphological and structural abnormalities of the mucosa, tumors and other major disorders.Here we review the progress of AI applications in geriatric digestive diseases affecting digestive organs and the mucosa in light of morphology and function, to provide a reference for reducing the incidence of both geriatric emergencies and GT.

[Clinical characteristics of digestive system cancers metastatic to the heart].

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.

Association of Low Handgrip Strength with Chemotherapy Toxicity in Digestive Cancer Patients: A Comprehensive Observational Cohort Study (FIGHTDIGOTOX).

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.

Therapeutic approach for digestive system cancers and potential implications of exercise under hypoxia condition: what little is known? a narrative review.

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.