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Background: The controlled nutritional status score (CONUT) and handgrip strength (HGS) were both predictive indexes for the prognosis of cancers. However, the combination of CONUT and HGS for predicting the prognosis of gastrointestinal cancer had not been developed. This study aimed to explore the combination of CONUT and HGS as the potential predictive prognosis in patients with gastric and colorectal cancer., Methods: A cohort study was conducted with gastric and colorectal cancer patients in multicenter in China. Based on the optimal HGS cutoff value for different sex, the HGS cutoff value was determined. The patients were divided into high and low HGS groups based on their HGS scores. A CONUT score of 4 or less was defined as a low CONUT, whereas scores higher than 4 were defined as high CONUT. The Kaplan-Meier method was used to create survival curves, and the log-rank test was used to compare time-event relationships between groups. A Cox proportional hazard regression model was used to determine independent risk factors for overall survival (OS)., Results: A total 2177 gastric and colorectal patients were enrolled in this study, in which 1391 (63.9%) were men (mean [SD] age, 66.11 [11.60] years). Multivariate analysis revealed that patients with high HGS had a lower risk of death than those with low HGS (hazard ratio [HR],0.87; 95% confidence interval [CI], 0.753-1.006, P = 0.06), while high CONUT had a higher risk of death than those with low CONUT (HR, 1.476; 95% CI, 1.227-1.777, P < 0.001). Patients with both low HGS and high CONUT had 1.712 fold increased risk of death (HR, 1.712; 95% CI, 1.364-2.15, P < 0.001). Moreover, cancer type and sex were stratified and found that patients with high CONUT and low HGS had lower survival rate than those with low CONUT and high HGS in both gastric or colorectal cancer, and both male and female., Conclusion: A combination of low HGS and high CONUT was associated with poor prognosis in patients with gastrointestinal cancer, which could probably predict the prognosis of gastrointestinal cancer more accurate than HGS or CONUT alone., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background/aim: The significance of spirometry as preoperative risk assessment for gastrointestinal surgery has been controversial. At the beginning of the COVID-19 pandemic, preoperative spirometry was temporarily suspended in our institute. This study was aimed to investigate the necessity of spirometry for gastrointestinal cancer surgery., Patients and Methods: We compared short-term postoperative outcomes between 318 patients who underwent surgery for colorectal or gastric cancer with (Spirometry group; n=272) or without spirometry (Non-spirometry group; n=46)., Results: Respiratory functional disorders were detected in 77 (28.3%) patients in the Spirometry group. No significant differences were noted in complications, including pneumonia, or the length of hospital stay between the two groups. An advanced age, male sex, comorbidities with respiratory diseases, and a smoking history significantly correlated with abnormal results in spirometry., Conclusion: Preoperative spirometry may be substituted with other clinical factors in patients with gastrointestinal cancer., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Gastrointestinal (GI) cancer patients often experience severe malnutrition during cancer therapies due to gastrointestinal dysfunctions including poor digestion and absorption as well as tumor-associated anorexia. In this study, we performed a randomized clinical trial to determine the efficacy of oral nutrition supplement (ONS) enriched with omega-3 fatty acids on nutritional status, quality of life (QOL), and pro-inflammatory indices., Methods: Patients diagnosed with GI cancers were recruited and screened for eligibility. A total of 58 patients were randomly allocated to either the control group (n=27) or the experimental group (n=31). The intervention group received 200 ml ONS twice a day while the control group received routine care. Anthropometrics, Patient-Generated Subjective Global Assessment (PG-SGA) score, QOL score and nutrient intake data were collected at baseline, week 4 and week 8. Blood was drawn for biochemical assessments. Nine patients from each group dropped out of the study Forty patients (18 control patients and 22 intervention patients) completed the study., Results: This study showed that ONS intervention improved PG-SGA scores in the intervention group (p<0.01). Scores of physical functioning score and role functioning were declined only in the control group and the difference between week 8 and baseline for role functioning was significant (p<0.001). Fatigue score was steadily decreased in the experiment group, and the differences between week 8 and baseline was significant between two groups (p<0.02). However, no statistically significant improvement in biochemical markers of nutritional status and pro-inflammatory cytokine concentrations were found. These results suggests that ONS intervention for 8 weeks improves PG-SGA scores and QOL scores in patients undergoing cancer therapy.

Background: Despite the known association between muscle mass/function and malnutrition-related mortality in upper gastrointestinal (UGI) cancer, no comprehensive study to determine the impact of muscle mass-dominant nutritional status on cancer prognosis has been conducted. The present study aimed to investigate the prognostic significance of integrated muscle mass and function in UGI cancer., Methods: Between July 2013 and March 2018, we enrolled 2546 cancer patients with risks of malnutrition (Nutrition Risk Screening 2002, ≥3 points) from a multicenter cohort study and split 527 patients with primary UGI cancer into an internal validation group. We prospectively performed instant nutritional assessment and recorded all general clinical characteristics of the participants, such as weight loss, body mass index, anthropometric measurements of muscle mass and function, dietary intake conditions, and disease burden and/or inflammation status based on the validated tools. Prognostic analyses were performed with post-assessment overall survival (OS)., Results: According to the entire set, UGI cancer was identified as the dominant risk factor for disease burden and inflammation criteria (hazard ratio (HR), 2.08, 95% confidence interval (Cl), 1.81-2.39, P < 0.001). Integrated muscle mass/function analysis with validated cutoff values showed that hand grip strength/weight followed by triceps skinfold thickness and maximum calf circumference are the most potent predictors. Univariate and multivariate analyses revealed that reduced muscle mass/function (74.8%) and dietary intake (66.2%) independently affect OS of patients with UGI cancer. Significant associations were found between the reduced muscle mass/reduced dietary intake and the shortest OS (HR, 4.48; 95% Cl, 3.07-6.53; P < 0.001). Appending subgroups of muscle mass/function and dietary intake to the pre-existing risk model increased the efficiency of the time-dependent receiver operating characteristic curve analysis for OS in UGI cancer, particularly within 2 years of instant nutritional assessment., Conclusion: Impaired muscle mass/function adversely affects the near-term prognosis in patients with UGI cancer. Along with a comprehensive evaluation of dietary intake conditions, the timely nutritional assessment might be useful for risk stratification of UGI cancers with potential for enteral and parenteral nutrition interventions., Registration Number: ChiCTR1800020329., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Identification of low muscle mass becomes increasingly relevant due to its prognostic value in cancer patients. In clinical practice, mid-upper arm muscle circumference (MAMC) and bioelectrical impedance analysis (BIA) are often used to assess muscle mass. For muscle-mass assessment, computed tomography (CT) is considered as reference standard. We investigated concordance between CT, BIA, and MAMC, diagnostic accuracy of MAMC, and BIA to detect low muscle mass and their relation with the clinical outcome malnutrition provided with the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF). This cross-sectional study included adult patients with advanced esophageal and gastrointestinal cancer. BIA, MAMC, and PG-SGA-SF were performed. Routine CT-scans were used to quantify psoas muscle index (PMI) and skeletal muscle area. Good concordance was found between CT PMI and both BIA FFMI (fat free mass index) (ICC 0.73), and BIA ASMI (appendicular skeletal muscle index) (ICC 0.69) but not with MAMC (ICC 0.37). BIA FFMI (94%), BIA ASMI (86%), and MAMC (86%) showed high specificity but low sensitivity. PG-SGA-SF modestly correlated with all muscle-mass measures (ranging from -0.17 to -0.43). Of all patients with low muscle mass, 62% were also classified with a PG-SGA-SF score of ≥4 points. Although CT remains the first choice, since both BIA and MAMC are easy to perform by dieticians, they have the potential to be used to detect low muscle mass in clinical practice.

The gastrointestinal tract comprises a complex ecosystem with extensive opportunities for functional interactions between neoplastic epithelial cells and stromal, immune, neuronal, glial, and other cell types, as well as microorganisms and metabolites within the gut lumen. In this Review, we focus on interactions between gastrointestinal cancers and elements of the central and enteric nervous systems. This previously understudied but rapidly emerging area of investigation has blossomed in recent years, particularly with respect to improved understanding of neural contributions to the development and progression of esophageal, gastric, pancreatic, and colon neoplasia. Cancer neuroscience offers great promise to advance our understanding of how neural-cancer interactions promote alimentary tract neoplasia. The resulting mechanistic insights can be leveraged to identify diagnostic and prognostic biomarkers, and to develop novel therapeutic interventions.

Purpose of the Review: Primary GI lymphomas of B cell origin are a diverse group of lymphomas. In this article, we provide an overview of the diagnosis, pathologic and molecular features, and management of these varied lymphomas., Recent Findings: The most common primary GI lymphomas are diffuse large B cell lymphoma (DLBCL) and marginal zone lymphomas (MZL), but follicular lymphomas (FL), mantle cell lymphomas (MCL), post-transplant lymphoproliferative disorders (PTLD), and Burkitt lymphoma of the GI tract also occur. Many features of these lymphomas are similar to their nodal counterparts, but certain clinical and biological aspects are unique. Diagnostic and treatment strategies for these lymphomas continue to evolve over time. There are ongoing discoveries about the unique pathophysiology, molecular characteristics, and complications of primary B cell GI lymphomas that are already leading to improvements in management of this histologically diverse set of lymphomas.

Background/aim: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common chemotoxicities. However, no effective clinical CIPN screening methods have been reported. This study aimed to investigate whether changes in heart rate variability (HRV) could predict the development of CIPN for early symptom control in chemotherapy-prescribed patients with gastrointestinal (GI) cancer., Patients and Methods: Fifty-five GI cancer outpatients undergoing palliative chemotherapy including taxanes and/or platinum compounds were enrolled. CIPN was diagnosed using National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE). HRV measures were derived from electrocardiogram signals., Results: Twelve weeks after starting chemotherapy, 39 (70.9%) patients who complained of NCI-CTCAE grade 1-3 sensory changes were diagnosed with CIPN. Standard deviation of normal-to-normal R-R intervals (SDNN), high frequency (HF), low frequency (LF), and LF/HF ratio changed significantly during 3 assessment periods. Percentage changes in SDNN and HF were related to the occurrence of CIPN symptoms. A decision tree model indicated that patients with a rapid percentage change decrease in SDNN and HF were CIPN-positive., Conclusion: Using SDNN and HF, our decision tree predicted CIPN occurrence. The changes in HRV may occur earlier than sensory CIPN symptoms., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The standard treatment for gastrointestinal cancer is surgical resection and perioperative adjuvant treatment. Multidisciplinary treatment for gastrointestinal cancer leads to body composition changes. Body composition changes, such as skeletal muscle loss and body weight loss, during multidisciplinary treatment result in poor physical activity, severe toxicity of chemotherapy and/or radiation therapy, and poor oncological outcomes. Therefore, the hypothesis is that minimization of body composition changes during multidisciplinary treatment in gastrointestinal cancer patients, the continuation of postoperative adjuvant treatment in these patients might improve, thereby improving the oncological outcomes. Given this hypothesis, recent studies have focused on introducing perioperative oral nutritional treatment for gastrointestinal cancer patients. Thus far, oral nutritional treatment has proven promising and showed some clinical benefits for gastrointestinal cancer patients during the perioperative period. However, whether or not oral nutritional treatment has clinical benefits on the long-term oncological outcomes in gastrointestinal cancer remains unclear. To optimize oral nutritional treatment for gastrointestinal cancer patients, it is necessary to clarify the benefits of oral nutritional treatment on the long-term oncological outcomes in gastric cancer patients and establish the optimal approach to oral nutritional treatment.

Background: Functional impairments (measured by activities of daily living [ADLs]) and health-related quality of life (HRQOL) may complicate outcomes in older adults diagnosed with cancer. In this retrospective cohort analysis, we characterized ADLs and HRQOL in adults older than 65 y with upper gastrointestinal (UGI) cancers and evaluated for an association to cancer-specific survival., Materials and Methods: Patients with UGI cancers aged 65 y or older were selected from the Surveillance, Epidemiology and End Results and the Medicare Health Outcomes Survey-linked database. Demographics, comorbidities, stage, ADLs, and HRQOL were summarized by patients managed with and without surgery. Because of the wide variety of cancers, we subdivided patients into cohorts of esophagogastric [EG; n = 88] or hepatobiliary/pancreatic [n = 68]. Cancer-specific survival curves were modeled for changes in ADL and HRQOL scores after diagnosis. Risk factors for cancer-specific survival were assessed with hazard ratios (HRs) and adjusted for demographics, stage, comorbidities, and disease cohorts., Results: HRQOL scores declined after diagnosis, with a sharper decline in nonsurgery patients. On multivariate analysis, inability to perform specific ADLs was associated with worse survival in multiple cohorts: hepatobiliary/pancreatic nonsurgery patients unable to eat (HR 3.3 95% confidence interval (CI) 1.7-6.5); all patients with EG unable to use the toilet (HR 3.3 95% CI 1.5-7.9); EG nonsurgery cohort unable to dress or use the toilet (dress HR 14.1 95% CI 4.0-49.0; toilet HR 4.7 95% CI 1.8-12.3)., Conclusions: Older survivors with UGI cancers report declines in HRQOL, especially those not undergoing surgery. The ability to perform ADLs may be linked to survival in this population., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: High protein diet (HDP) promotes improvement of lean body mass in elderly without cancer; but the impact of high protein intake on muscle strength and mortality in cancer patients remains to be elucidated. This study evaluates the association between HPD on handgrip strength (HGS) and survival in older adults outpatients with advanced gastrointestinal cancer., Methods: Ninety-one patients with advanced gastrointestinal cancer (>65% tumor stage III-IV) undergoing radiotherapy, chemotherapy or surgery were enrolled. Upon first oncological visit, tumor stage was assessed by a physician. Then, a nutritionist or a dietitian measured the body mass index (BMI), HGS by means of a dynamometer, and dietary food intake by using 24h food recall. Patients were stratified in HPD (i.e, ≥1.5 g/kg/d) or low protein diet (LPD: <1.5 g/kg/d). Kaplan-Meier curve was used to assess the survival since the cancer diagnosis., Results: HPD was reported by approximately 30% of patients. Protein intake was significantly higher in HPD vs LPD patients (2.2 ± 0.8 vs. 0.8 ± 0.4 g/kg/d, respectively; p < 0.0001). No significant association was found between HPD and HGS, even after adjustment for physical activity, alcohol intake, smoking, sex, age, tumor stage, oncologic treatment and BMI (OR: 0.97 [95%CI: 0.88-1.08], p = 0.64), or for energy intake kcal/kg/day, leucine g/d and lipids g/d (OR: 0.93 [95%CI: 0.85-1.03, p = 0.19]. In addition, HPD group showed higher overall survival than LPD group (HPD: 14.7 vs. LPD: 7.3 months, p = 0.04)., Conclusion: HPD is not associated with better muscle function as measured by HGS, but with overall survival in older adults outpatients with advanced gastrointestinal cancer. HPD may represent a strategy to mitigate the cancer-induced mortality and should be further explored., Competing Interests: Conflict of interest The authors declare that they do not have conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background & Aims: The evaluation of function and muscle mass in older cancer patients is essential to reduce comorbidities. We hypothesized that Simple Questionnaire to Rapidly Diagnose Sarcopenia (SARC-F) questionnaire is useful to assessment the muscle function, but not muscle mass. Thus, the purpose of this study was to evaluate the correlation and reliability between the SARC-F and skeletal muscle mass index (SMI) in older gastrointestinal cancer patients., Methods: A cross-sectional observational study enrolled 108 (63.55 ± 8.9 y) gastrointestinal cancer patients. The patients were evaluated using the SARC-F questionnaire and the muscle mass index (SMI). SMI was calculated using Lee's equation: the appendicular muscle mass (ASM) was divided by height. Pearson's correlation was used to examine the correlation between SARC-F and SMI. The Bland-Altman plot and Cohen's kappa coefficient were used to determine the concordance and reliability between them. Statistical difference was set at p < 0.05., Results: The Bland-Altman plot showed that the difference between methods were within agreement (±1.96; p = 0.001). However, SARC-F has low concordance (κ = 0.20; standard error = 0.14) and correlation (r = -0.303; p = 0.0014) with SMI., Conclusion: In older cancer outpatients, we found that SARC-F has low correlation and reliability with SMI., Competing Interests: Conflict of interest The authors declare no funding sources or conflicts of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Nutrition and gastrointestinal cancer are inextricably linked. The metabolic effects of cancer along with changes in dietary intake, the development of cancer cachexia and the presence of sarcopenia can influence changes in body composition. These have a negative impact on quality of life and tolerance to cancer treatment. Treatment for cancer presents some significant nutritional challenges as nutrition impact symptoms may develop, be exacerbated by treatment and may contribute to a worsening in nutritional status. Nutrition screening and assessment should be an integral part of holistic patient care. The provision of appropriate, evidence-based dietary advice should occur before, during and after cancer treatment. Appropriate and timely methods of nutritional support across the spectrum of gastrointestinal cancer are needed to ensure that people are adequately supported during courses of treatment that can span weeks and months. These can range from standard approaches of supplementing oral intake to complex interventions such as managing high output intestinal stomas. The gastrointestinal tract is particularly susceptible to impact from systemic anti-cancer treatments and radiotherapy. Gastrointestinal late effects of cancer treatment are now recognised to present particular challenges in terms of both medical and nutritional management. These late effects have a significant impact on the individual and their quality of life in addition to implications for the health service. Dietary intake following cancer treatment has an impact on quality of life and future research may demonstrate its influence on the risk of recurrence of gastrointestinal cancer.

Background: Patients suffering from gastrointestinal cancer comprise a large group receiving home hospice care in China, however, little is known about the prediction of their survival time. This study aimed to develop a gastrointestinal cancer-specific non-lab nomogram predicting survival time in home-based hospice., Methods: We retrospectively studied the patients with gastrointestinal cancer from a home-based hospice between 2008 and 2018. General baseline characteristics, disease-related characteristics, and related assessment scale scores were collected from the case records. The data were randomly split into a training set (75%) for developing a predictive nomogram and a testing set (25%) for validation. A non-lab nomogram predicting the 30-day and 60-day survival probability was created using the least absolute shrinkage and selection operator (LASSO) Cox regression. We evaluated the performance of our predictive model by means of the area under receiver operating characteristic curve (AUC) and calibration curve., Results: A total of 1618 patients were included and divided into two sets: 1214 patients (110 censored) as training dataset and 404 patients (33 censored) as testing dataset. The median survival time for overall included patients was 35 days (IQR, 17-66). The 5 most significant prognostic variables were identified to construct the nomogram among all 28 initial variables, including Karnofsky Performance Status (KPS), abdominal distention, edema, quality of life (QOL), and duration of pain. In training dataset validation, the AUC at 30 days and 60 days were 0.723 (95% CI, 0.694-0.753) and 0.733 (95% CI, 0.702-0.763), respectively. Similarly, the AUC value was 0.724 (0.673-0.774) at 30 days and 0.725 (0.672-0.778) at 60 days in the testing dataset validation. Further, the calibration curves revealed good agreement between the nomogram predictions and actual observations in both the training and testing dataset., Conclusion: This non-lab nomogram may be a useful clinical tool. It needs prospective multicenter validation as well as testing with Chinese clinicians in charge of hospice patients with gastrointestinal cancer to assess acceptability and usability.

Gastrointestinal (GI) cancers, leading causes of cancer-related deaths, have been serious challenging human diseases up to now. Because of high rates of mortality, late-stage diagnosis, metastasis to distant locations, and low effectiveness and adverse events of routine standard therapies, the quality of life and survival time are low in patients with GI cancers. Hence, many efforts need to be done to explore and find novel efficient treatments. Beneficial effects of melatonin have been reported in a wide variety of human diseases. Melatonin has antioxidant, anti-inflammatory, antimicrobial, and anticancer effects. Various studies have showed the regulatory effects of melatonin on apoptotsis, autophagy and angiogenesis; these properties result in the inhibition of invasion, migration, and proliferation of GI cancer cells in vivo and in vitro. Together, this review suggests that melatonin in combination with anticancer agents may improve the efficacy of routine medicine and survival rate of patients with cancer., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background/aim: Precise tumor localization during gastrointestinal surgery improves curability and function preservation. We investigated the efficacy of preoperative endoscopic fluorescent clip marking using a Zeoclip FS with built-in near-infrared fluorescent resins in delineating gastrointestinal cancer for surgery., Patients and Methods: We evaluated the intraoperative visibility of the Zeoclip FS using a VISERA ELITE 2 and the short-term outcomes of 37 cancer patients (colorectal, n=23; gastric, n=14) who underwent preoperative fluorescent clip marking., Results: The study included 23 male and 14 female subjects with a mean age of 73 years (range=39-87 years). Thirty-three patients (89.1%) exhibited clear fluorescent clip marking and easily determined transection lines. Fluorescence was not observed in 1 sigmoid colon cancer patient (2.7%), who required a colonic stent for preoperative obstruction. Three patients (8.1%) required additional procedures for fluorescence visualization., Conclusion: Endoscopic fluorescent clip marking can delineate tumors well for determining the extent of resection., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Glycemic variability is associated with risks for adverse events in patients with cancer. Several studies have evaluated the presence and impact of hyperglycemia and/or hypoglycemia in patients with cancer; however, few studies have evaluated glycemic variability. The purpose of this integrative review of studies in patients with gastrointestinal cancers was to investigate the presence and methods of reporting glycemic variability during and following treatments., Methods: A comprehensive review of the literature was conducted. PubMed, CINAHL, EMBASE, and Cochrane databases were searched for publications between 1/1/1969 and 7/24/2019. Studies of patients with gastrointestinal cancer following surgery, during treatment, and <5 years following treatment were included and evaluated by cancer type and method of glucose and glycemic variability measurement., Results: Among 1526 patients with gastrointestinal cancer across 19 studies, gastric and pancreatic cancers were most prevalent. Timing of glucose testing and methods of analyzing glycemic variability varied. Most analyses used the standard deviation or interquartile range. Glycemic variability was more prevalent among patients with Type 2 Diabetes and among those with pancreatic cancer. In some patients glycemic variability remained notable > one year following surgery despite improvements in glycemic control., Conclusion: Patients with gastrointestinal cancer experience glycemic variability during and up to one year following treatment. There was heterogeneity in methods related to timing of testing and reporting glycemic variability among the 19 studies in this review. Future investigations need to identify the presence and define the methods of measuring glycemic variability in patients with gastrointestinal cancer., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Over the past 5 years, a number of notable research advances have been made in the field of neuroendocrine cancer, specifically with regard to neuroendocrine cancer of the gastrointestinal tract. The aim of this Review is to provide an update on current knowledge that has proven effective for the clinical management of patients with these tumours. For example, for the first time in the tubular gastrointestinal tract, well-differentiated high-grade (grade 3) tumours and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are defined in the WHO classification. This novel classification enables efficient identification of the most aggressive well-differentiated neuroendocrine tumours and helps in defining the degree of aggressiveness of MiNENs. The Review also discusses updates to epidemiology, cell biology (including vesicle-specific components) and the as-yet-unresolved complex genetic background that varies according to site and differentiation status. The Review summarizes novel diagnostic instruments, including molecules associated with the secretory machinery, novel radiological approaches (including pattern recognition techniques), novel PET tracers and liquid biopsy combined with DNA or RNA assays. Surgery remains the treatment mainstay; however, peptide receptor radionuclide therapy with novel radioligands and new emerging medical therapies (including vaccination and immunotherapy) are evolving and being tested in clinical trials, which are summarized and critically reviewed here.

Hippo signaling pathway is highly conservative in evolution. MST1/2, LATS1/2, and the effector protein YAP/TAZ are the core members of this signaling pathway in mammalian cells. There have been many studies on YAP/TAZ and its downstream, however, the upstream regulatory factors of the Hippo signaling pathway remain unclear, and become one of the hot research directions of this pathway at present. In addition, Hippo signaling pathway can cross-talk with other signaling pathways such as Wnt and Notch signaling pathways, and plays an important role in controlling organ size, maintaining tissue homeostasis, and promoting tissue repair and regeneration. Abnormal Hippo signaling pathway may lead to the occurrence of a variety of tumors, especially gastrointestinal cancers such as liver cancer, colorectal cancer and gastric cancer. The abnormal expression of its members in gastrointestinal cancers is related to cancer cell proliferation, apoptosis, invasion and migration. Hippo signaling pathway is vital for liver repair and regeneration. Its inactivation will lead to the occurrence of primary liver cancer. The mechanism of YAP in liver cancer mainly depends on TEAD-mediated gene transcription. Hippo signaling pathway is also important for maintaining intestinal homeostasis, and its imbalance can lead to the occurrence and recurrence of colorectal cancer. In primary and metastatic gastric cancer, the expression of YAP/TAZ is significantly up-regulated, but the specific molecular mechanism is unclear. This article summarizes the recent progress on Hippo signaling pathway and its upstream regulatory factors, its roles in the development of gastrointestinal cancers and related molecular mechanisms; and also discusses the future research directions of Hippo signaling pathway.

Objectives: Patients with cancer are susceptible to experiencing the loss of skeletal muscle mass. Thus, the purpose of this study was to evaluate whether a high-protein diet (HPD) or isolated branched-chain amino acid (BCAA) intake is associated with an increased skeletal muscle mass index (SMI) in patients with cancer of the gastrointestinal tract., Methods: This cross-sectional, observational study included 106 patients with gastrointestinal tract tumors. Food consumption was estimated using 24-h food recall. Patients were divided into two groups: a low-protein diet (LPD) group (≤1.2 g · kg · d -1 ) and a high-protein diet (HPD) group (>1.2 g · kg · d -1 ). Appendicular muscle mass (ASM) was calculated using Lee's formula, and its values were divided by the square of the height of the patient to obtain SMI values. Differences were considered significant when the probability they occurred by chance was <5% (P < 0.05)., Results: Of 106 patients assessed, 69 (65%) consumed a diet consistent with specifications of the LPD group and 37 (35%) consumed a diet consistent with HPD intake. Logistic regression after adjusting for sex and caloric and carbohydrate consumption showed an association between SMI and HPD (odds ratio, 4.19; 95% confidence interval, 1.06-16.56; P < 0.001) but not with BCAA. Daily total protein intake, but not isolated BCAA or leucine, was able to predict an increase in SMI in 43% of patients considered (P = 0.006). Thus, HPD was associated with SMI, and total protein intake was a better predictor of SMI than BCAAs., Conclusion: HPD is a cost-effective way to enhance SMI, rather than focusing on the ingestion of isolated BCAAs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study was designed to evaluate the psychometric properties of the newly completed Japanese translation of the Ferrans and Powers Quality of Life Index Cancer Version III (QLI). Using a cross-sectional descriptive design, 136 ambulatory patients with gastrointestinal cancer (55 receiving chemotherapy, 76 with stable health status after treatment, and five status not known) completed a questionnaire at a one-time point, and 26 patients (stable health status) completed the questionnaire again 2 weeks later. Internal consistency reliability was supported by Cronbach's α of .96 for the total scale, with subscales ranging from .83 to .93. A test-retest correlation of 0.76 (total scale) provided evidence of stability reliability over a 2-week period, with subscale retest correlations ranging from 0.70 to 0.83. Confirmatory factor analysis showed the same four domains for the Japanese translation as the original QLI, supporting construct validity. We also assessed construct validity by examining the relationships between the Japanese QLI and six other concepts known to be related to the quality of life. As hypothesized, all correlations were moderate and in the expected direction (pain -0.39, anxiety -0.54, depression -0.63, stress -0.51, pain interfering with functioning -0.52, and general health 0.62). This evidence of the reliability and validity of the Japanese translation of the QLI supports its use in research and clinical practice to evaluate the impact of cancer and treatment. This new translation can be used to assess the patient's perspective of their quality of life, both within Japan and in cross-cultural studies with the QLI in other languages., (© 2020 Wiley Periodicals, Inc.)

Objective: Gait is a sensitive marker for functional declines commonly seen in patients treated for advanced cancer. We tested the effect of a combined exercise and nutrition programme on gait parameters of advanced-stage cancer patients using a novel wearable gait analysis system., Methods: Eighty patients were allocated to a control group with nutritional support or to an intervention group additionally receiving whole-body electromyostimulation (WB-EMS) training (2×/week). At baseline and after 12 weeks, physical function was assessed by a biosensor-based gait analysis during a six-minute walk test, a 30-s sit-to-stand test, a hand grip strength test, the Karnofsky Index and EORTC QLQ-C30 questionnaire. Body composition was measured by bioelectrical impedance analysis and inflammation by blood analysis., Results: Final analysis included 41 patients (56.1% male; 60.0 ± 13.0 years). After 12 weeks, the WB-EMS group showed higher stride length, gait velocity (p < .05), six-minute walking distance (p < .01), bodyweight and skeletal muscle mass, and emotional functioning (p < .05) compared with controls. Correlations between changes in gait and in body composition, physical function and inflammation were detected., Conclusion: Whole-body electromyostimulation combined with nutrition may help to improve gait and functional status of cancer patients. Sensor-based mobile gait analysis objectively reflects patients' physical status and could support treatment decisions., (© 2019 John Wiley & Sons Ltd.)

Long thought to be dispensable after establishing X chromosome inactivation (XCI), Xist RNA is now known to also maintain the inactive X (Xi). To what extent somatic X reactivation causes physiological abnormalities is an active area of inquiry. Here, we use multiple mouse models to investigate in vivo consequences. First, when Xist is deleted systemically in post-XCI embryonic cells using the Meox2-Cre driver, female pups exhibit no morbidity or mortality despite partial X reactivation. Second, when Xist is conditionally deleted in epithelial cells using Keratin14-Cre or in B cells using CD19-Cre, female mice have a normal life span without obvious illness. Third, when Xist is deleted in gut using Villin-Cre, female mice remain healthy despite significant X-autosome dosage imbalance. Finally, when the gut is acutely stressed by azoxymethane/dextran sulfate (AOM/DSS) exposure, both Xist -deleted and wild-type mice develop gastrointestinal tumors. Intriguingly, however, under prolonged stress, mutant mice develop larger tumors and have a higher tumor burden. The effect is female specific. Altogether, these observations reveal a surprising systemic tolerance to Xist loss but importantly reveal that Xist and XCI are protective to females during chronic stress., Competing Interests: Competing interest statement: J.T.L. is a cofounder of Translate Bio and Fulcrum Therapeutics, and an advisor to Skyhawk Therapeutics. To our knowledge, none of the companies is presently working on Xi reactivation.

Objective The feasibility of continuous geriatric assessments (GAs) has not been evaluated fully in elderly patients with cancer. We prospectively investigated this issue by administering a recommended-GA set (r-GA) repeatedly to patients undergoing chemotherapy for gastrointestinal cancer on an outpatient basis. Methods We administered the r-GA before chemotherapy and every two months thereafter. Continuous GAs was defined as the completion of at least two assessments, including the pre-treatment evaluation. The r-GA included the Barthel Index [Basic Activities of Daily Living (BADL)], Mini-Mental State Examination-Japanese (MMSE-J), Instrumental Activities of Daily Living (IADL) scale, Vitality Index (VI), and Geriatric Depression Scale-15. We also used the Vulnerable Elders Survey (VES)-13 to screen overall vulnerability. We analyzed the correlations between each baseline GA score and the overall survival (OS) and the association between the OS and changes in each patient's GA scores over time. Patients Patients ≥65 years of age who presented to our department for initial consultation were enrolled and followed between December 2012 and January 2017. Results Twenty-one elderly patients (median age, 76 years old) were enrolled. GAs were completed within 20 minutes. In an age- and performance status (PS)-adjusted Cox proportional hazards analysis, the baseline BADL, MMSE-J, and VI scores correlated significantly with the OS (p=0.012, p=0.032, and p=0.012, respectively). During the clinical course, decreases in the MMSE-J and VES-13 scores were correlated with the OS (p=0.022 and p=0.019, respectively). Conclusion Outpatient GA administration is feasible. Low baseline BADL, MMSE-J, and VI scores and decreased MMSE-J and VES-13 scores over time may prognosticate the OS.

The aim of this study was the quantitative evaluation of gastrointestinal cancer cell motility and 5-aminolevulinic acid (5-ALA)-induced fluorescence in vitro using mathematical morphology and structural analysis methods. The results of our study showed that MKN28 cells derived from the lymph node have the highest motility compared with AGS or HCT116 cells derived from primary tumors. Regions of single cells were characterized as most moving, and "tightly packed" cell colonies as nearly immobile. We determined the reduction of cell motility in late passage compared to early passage. Application of 5-ALA caused fluorescence in all investigated cells, and the fluorescence was different with regard to the cell type and application time. We observed higher fluorescence in MKN28 cells. Comprehensive image analysis did not reveal any statistically significant difference in fluorescence intensity between "tightly packed" cell regions, where nearly no motility was registered and loosely distributed cells, where the highest cell motility was registered. In conclusions, our study revealed that MKN28 cells derived from the lymph node have higher motility and 5-ALA-induced fluorescence than AGS or HCT116 derived from primary tumors. Moreover, image analysis based on a large amount of processed data is an important tool to study these tumor cell properties.

Objectives: Gastrointestinal tract (GIT) lymphoma is associated with a risk for perforation while the patient is receiving chemotherapy. The role of total parenteral nutrition (TPN) and bowel rest in preventing perforation is unknown. The aim of this study was to examine the clinical outcomes of TPN and bowel rest in patients with GIT lymphoma who were receiving chemotherapy., Methods: We reviewed all patients with GIT biopsy-proven lymphoma in our institution between 2013 and 2017. Patients were stratified into two groups, with and without TPN and bowel rest during chemotherapy. We identified 158 patients with GIT lymphoma. Of these, 47 (29.7%) received TPN and bowel rest before chemotherapy. Patients who received TPN were younger, more likely to have aggressive lymphoma in the small or large bowel. The primary outcome was to compare the perforation rate between the two groups. Secondary outcome analysis included infection rate and survival., Results: Patients with perforation had significantly poorer survival. Perforation rate was similar between the TPN and the non-TPN groups (8.5% versus 2.7%, P = 0.197). Overall survival was similar between the two groups (P = 0.659). The TPN group had a higher infection rate (odds ratio, 5.32; 95% confidence interval, 1.36-20.8) after adjustment for covariates (age, types of lymphoma, and location of lymphoma)., Conclusion: The present study demonstrated that TPN and bowel rest did not reduce the risk for perforation among patients with GIT lymphoma who were receiving chemotherapy. As the practice of prophylactic TPN and bowel rest was associated with higher infection risk and longer hospitalization, we do not recommend such practice for all patients with GIT lymphoma receiving chemotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Werner syndrome (WS) is an autosomal recessive progeroid disease characterized by patients' early onset of aging, increased risk of cancer and other age-related pathologies. WS is caused by mutations in WRN, a RecQ helicase that has essential roles responding to DNA damage and preventing genomic instability. While human WRN has both an exonuclease and helicase domain, Drosophila WRNexo has high genetic and functional homology to only the exonuclease domain of WRN. Like WRN-deficient human cells, Drosophila WRNexo null mutants (WRNexo Δ ) are sensitive to replication stress, demonstrating mechanistic similarities between these two models. Compared to age-matched wild-type controls, WRNexo Δ flies exhibit increased physiological signs of aging, such as shorter lifespans, higher tumor incidence, muscle degeneration, reduced climbing ability, altered behavior, and reduced locomotor activity. Interestingly, these effects are more pronounced in females suggesting sex-specific differences in the role of WRNexo in aging. This and future mechanistic studies will contribute to our knowledge in linking faulty DNA repair mechanisms with the process of aging., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Worsening nutritional status in older adult cancer patients can lead to sarcopenia, a condition that occurs with low quantity or quality of muscle mass associated with low physical function. However, most of the studies with cancer patients have only analyzed the quantity of muscle mass for diagnostic of sarcopenia, without exploring muscle characteristics and physical function. The purpose of the present study is to explore the associations between muscle mass characteristics and physical function in older adult patients with cancer., Methods: Gastric older cancer patients were enrolled in a cross-sectional study. Computed tomography images of the abdominal region evaluated skeletal muscle mass using the Slice-O-Matic version 5.0 Software program (Tomovision, Montreal, Canada) to determine the parameters of skeletal muscle index (SMI, muscle quantity) and skeletal muscle radiodensity (SMD). The physical function was evaluated through handgrip strength and gait speed test. Four musculature phenotypes were identified: normal SMI and SMD, only low SMI, only low SMD, and low SMI and SMD. Linear regression analyses adjusted by age and tumor stage verified the associations between SMI, SMD and physical function. A One-Way Covariance Analysis with Bonferroni post hoc test was used to compare the physical function variables among the four different phenotypes., Results: In total, 167 patients were evaluated (58.1% males; mean age 69.17 ± 7.97 years). The results showed that muscle mass characteristics explains, at least partially, the variability in handgrip strength and gait speed in a direct relationship. The phenotypes with low muscular SMI and/or SMD presented worse performances in handgrip strength and gait speed tests. When stratified for sexes, the significant difference occurs only in males., Conclusions: Low SMD has negatively impacted physical function in older adults with gastrointestinal cancer, especially in males., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Amyloid A (AA) amyloidosis is found in humans and non-human primates, but quantifying disease risk prior to clinical symptoms is challenging. We applied machine learning to identify the best predictors of amyloidosis in rhesus macaques from available clinical and pathology records. To explore potential biomarkers, we also assessed whether changes in circulating serum amyloid A (SAA) or lipoprotein profiles accompany the disease. Methods: We conducted a retrospective study using 86 cases and 163 controls matched for age and sex. We performed data reduction on 62 clinical, pathological and demographic variables, and applied multivariate modelling and model selection with cross-validation. To test the performance of our final model, we applied it to a replication cohort of 2,775 macaques. Results: The strongest predictors of disease were colitis, gastrointestinal adenocarcinoma, endometriosis, arthritis, trauma, diarrhoea and number of pregnancies. Sensitivity and specificity of the risk model were predicted to be 82%, and were assessed at 79 and 72%, respectively. Total, low density lipoprotein and high density lipoprotein cholesterol levels were significantly lower, and SAA levels and triglyceride-to-HDL ratios were significantly higher in cases versus controls. Conclusion: Machine learning is a powerful approach to identifying macaques at risk of AA amyloidosis, which is accompanied by increased circulating SAA and altered lipoprotein profiles.

In vitro, cell cultures are essential tools in the study of intestinal function and disease. For the past few decades, monolayer cellular cultures, such as cancer cell lines or immortalized cell lines, have been widely applied in gastrointestinal research. Recently, the development of three-dimensional cultures known as organoids has permitted the growth of normal crypt-villus units that recapitulate many aspects of intestinal physiology. Organoid culturing has also been applied to study gastrointestinal diseases, intestinal-microbe interactions, and colorectal cancer. These models are amenable to CRISPR gene editing and drug treatments, including high-throughput small-molecule testing. Three-dimensional intestinal cultures have been transplanted into mice to develop versatile in vivo models of intestinal disease, particularly cancer. Limitations of currently available organoid models include cost and challenges in modeling nonepithelial intestinal cells, such as immune cells and the microbiota. Here, we describe the development of organoid models of intestinal biology and the applications of organoids for study of the pathophysiology of intestinal diseases and cancer.

The improvement of sleep quality in patients with cancer has a positive therapeutic effect on them. However, there are no specific treatment guidelines for treating sleep disturbance in cancer patients. We investigated the effect of forest therapy on the quality of sleep in patients with cancer. This study was conducted on nine patients (one male, eight female; mean age, 53.6 ± 5.8 years) with gastrointestinal tract cancer. All patients participated in forest therapy for six days. They underwent polysomnography (PSG) and answered questionnaires on sleep apnea (STOP BANG), subjective sleep quality (Pittsburgh Sleep Quality Index, PSQI), sleepiness (Stanford and Epworth Sleepiness Scales), and anxiety and depression (Hospital Anxiety and Depression Scale) to evaluate the quality of sleep before and after forest therapy. Sleep efficiency from the PSG results was shown to have increased from 79.6 ± 6.8% before forest therapy to 88.8 ± 4.9% after forest therapy ( p = 0.027) in those patients, and total sleep time was also increased, from 367.2 ± 33.4 min to 398 ± 33.8 min ( p = 0.020). There was no significant difference in the STOP BANG score, PSQI scores, daytime sleepiness based on the results of the Stanford and Epworth Sleepiness Scales, and depression and anxiety scores. Based on the results of this study, we suggest that forest therapy may be helpful in improving sleep quality in patients with gastrointestinal cancers.

Background/aim: DOG1 is a calcium-activated chloride channel that has gained attention as a promising drug target due to its involvement in several processes essential for tumor development and progression. DOG1 is overexpressed in >95% of gastrointestinal stromal tumors (GIST). The aim was to determine DOG1 inhibition antitumoral effects on GIST., Materials and Methods: Human GIST (GIST-T1 and GIST882) cell lines were used to study the effect of DOG1 inhibitors on chloride currents, viability, colony formation, and cell cycle., Results: CaCC inh -A01 decreased chloride currents. CaCC inh -A01 and T16 inh -A01 reduced GIST cell viability and CaCC inh -A01 affected cell cycle distribution leading to G 1 cell-cycle arrest. CaCC inh -A01 also increased the sub-G 1 phase population, indicative of apoptosis, in GIST882. CaCC inh -A01 strongly reduced the colony forming ability of the cells, whereas T16 inh -A01 did not., Conclusion: DOG1 inhibition has antitumoral effects in GIST cells in vitro, and could potentially serve as a target for GIST therapy., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: The purpose of this exploratory study was to identify the main dietary patterns of a Portuguese population of patients with gastrointestinal cancer and to analyze their association with sarcopenia., Methods: This was a prospective study with a consecutive sample of 100 patients with gastrointestinal cancer enrolled at diagnosis. Dietary intake was assessed with a semiquantitative Food Frequency Questionnaire, and dietary patterns were obtained with principal component analysis. Nutritional assessment was done using the Patient-Generated Subjective Global Assessment, and body composition was evaluated with anthropometric measures and computed tomography image processing obtained at the third lumbar vertebrae. Sex and body mass index specific cutoffs were used to define sarcopenia., Results: Four major patterns were identified: high-fat dairy products, fried snacks, and processed meat diet; legumes, vegetables, and fruit diet; fat and fish diet; and alcohol, cereal, and animal protein diet. On simple logistic regression, the occurrence of sarcopenia in participants in the second tertile (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.10-0.83; P = 0.02) and third tertile (OR 0.24; 95% CI 0.08-0.69; P = 0.01) of adherence to the high-fat and fish diet was reduced compared with the first tertile. On multiple logistic regression, the second tertile (OR 0.38, 95% CI 0.11-1.19; P = 0.10) of the fat and fish dietary pattern maintained a trend toward a reduction of the odds of sarcopenia compared with the first tertile, independently of calorie intake, age, disease location, and stage., Conclusions: The fat and fish dietary pattern was associated with lower odds of sarcopenia in this population of patients with gastrointestinal cancer., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Patients with neuroendocrine tumors (NETs) of the gastrointestinal tract suffer frequently from chronic diarrhea. A well characterized medical advice containing zeolite (Detoxsan ® powder) was applied to patients suffered from therapy-refractory diarrhea either by its frequency or by watery stool, despite receiving standard pharmacotherapy according to the guidelines for carcinoid syndrome and comorbidities. Detoxsan ® powder acts as an adsorbent and might reduce significantly symptoms of diarrhea in patients suffering from NETs., Aim: To overcome the therapy-refractory diarrhea of patients with NETs by the zeolite containing medical advice Detoxsan ® powder., Methods: A total of 20 patients (12 female and 8 male) suffering from diarrhea either by its frequency or from watery stool caused by NETs were included. In each patient, the diagnosis had been confirmed by histology and somatostatin receptors expression proven by positron emission tomography/computed tomography using Ga-68-labeled somatostatin analogs. All patients received standard-of-care pharmacotherapy and were additionally given Detoxsan ® powder as an extemporaneous drug containing 90% natural Cuban zeolite and 10% magnesium aspartate. Recommended daily dosage ranges between 3 g once to three times per day. Each day dose and bowel movements were documented by the patients themselves in a pre-defined table. Additionally to the bowel movements quantitative determinations of serotonin, urea, creatinine and single ions were performed within the serum of the patients by commercially available equipment used as a matter of routine in the clinic., Results: All patients enrolled in this pilot study did not only suffer from NETs, but also from comorbidities and treatment-resistant diarrhea. There was insufficient control of diarrhea, most probably due to the secretion of hormones like serotonin produced by the slowly growing and highly differentiated NETs. All patients only took Detoxsan ® powder as an antidiarrheal drug. In general, response effects need several days to become perceptible and require an intake of Detoxsan ® powder for an extended time period or intermittently, if persisting stabilization of bowel movements could not be achieved. A correlation between NET grade, part and size of bowel resection and functionality of the tumor could not be demonstrated. Therefore, diarrhea seemed to be based on the metabolic activity of the well-differentiated NETs, which eventually led to treatment resistance. In summary, 14 out of the 20 patients (70%) declared to be very content with using Detoxsan ® powder and observed a significant reduction of diarrhea, while the effective dose and intake period that resulted in a symptom relief varied individually., Conclusion: Detoxsan ® powder is able to reduce significantly symptoms of NET-related diarrhea in the majority of patients. The duration of taking Detoxsan ® powder and its dosage vary individually., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest. Dathe W is an external advisor for Heck Bio-Pharma GmbH and licenser for Detoxsan®.

Competing Interests: None

Gene expression patterns in cancer cells are strongly influenced by posttranscriptional mechanisms. RNA-binding proteins (RBPs) play key roles in posttranscriptional gene regulation; they can interact with target mRNAs in a sequence- and structure-dependent manner, and determine cellular behavior by manipulating the processing of these mRNAs. Numerous RBPs are aberrantly deregulated in many human cancers and hence, affect the functioning of mRNAs that encode proteins, implicated in carcinogenesis. Here, we summarize the key roles of RBPs in posttranscriptional gene regulation, describe RBPs disrupted in cancer, and lastly focus on RBPs that are responsible for implementing cancer traits in the digestive tract. These evidences may reveal a potential link between changes in expression/function of RBPs and malignant transformation, and a framework for new insights and potential therapeutic applications. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications., (© 2018 Wiley Periodicals, Inc.)

The tumour microenvironment, also termed the tumour stroma or tumour mesenchyme, includes fibroblasts, immune cells, blood vessels and the extracellular matrix and substantially influences the initiation, growth and dissemination of gastrointestinal cancer. Cancer-associated fibroblasts (CAFs) are one of the critical components of the tumour mesenchyme and not only provide physical support for epithelial cells but also are key functional regulators in cancer, promoting and retarding tumorigenesis in a context-dependent manner. In this Review, we outline the emerging understanding of gastrointestinal CAFs with a particular emphasis on their origin and heterogeneity, as well as their function in cancer cell proliferation, tumour immunity, angiogenesis, extracellular matrix remodelling and drug resistance. Moreover, we discuss the clinical implications of CAFs as biomarkers and potential targets for prevention and treatment of patients with gastrointestinal cancer.

Background: Abnormally high estimated glomerular filtration rates (eGFRs) are associated with endothelial dysfunction and frailty. Previous studies have shown that low eGFR is associated with increased morbidity, but few reports address high eGFR. The purpose of this study is to evaluate the association of high eGFR with surgical outcomes in patients undergoing surgery for gastrointestinal malignancies., Methods: We identified patients who underwent elective surgery for gastrointestinal malignancies from 2005 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program database. We evaluated associations of eGFR with surgical outcomes by Cox or logistic models with restricted cubic spline functions, adjusting for case mix variables (i.e. age, gender, race and diabetes)., Results: The median eGFR is 83 (interquartile range 67-96) mL/min/1.73 m2. Thirty-day mortality was 1.9% (2555/136 896). There is a U-shaped relationship between eGFR and 30-day mortality. The adjusted hazard ratios (95% confidence intervals) for eGFRs of 30, 60, 105 and 120 mL/min/1.73 m2 (versus 90 mL/min/1.73 m2) are 1.73 (1.52-1.97), 1.00 (0.89-1.11), 1.42 (1.31-1.55) and 2.20 (1.79-2.70), respectively. Similar associations are shown for other surgical outcomes, including return to the operating room and postoperative pneumonia. Subgroup analyses show that eGFRs both higher and lower than the respective medians are consistently associated with a higher risk of adverse outcomes across age, gender and race., Conclusions: High and low eGFRs are associated with more adverse surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. The eGFR associated with the lowest postoperative risk is approximately at the median eGFR of a given population., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background/aim: The purpose of this study was to determine sarcopenia, sarcopenic obesity and phase angle (PA) and the influence of chemotherapy (CT) on anthropometric measurements and and the PA in in geriatric patients with gastrointestinal (GI) cancer., Materials and Methods: The anthropometric measurements, calf circumference (CC), upper midarm circumference (UMAC), and hand grip strength (HGS), have been measured to understand muscle function of 153 patients (mean age of 70.5 ± 5.6 years, 28.8% female, 71.2% male). Sarcopenia and PA measurements have been evaluated by bioelectrical impedance analyses. The same evaluations were checked again after 1 cycle of CT (min: 4, max: 6 weeks)., Results: Patient population consisted of colorectal (51,6%), gastric (26.8%), pancreas (11.8%), liver (7.2%), and biliary tract cancer (2%). UMAC (28.5 ± 4.4 before, 28.1 ± 4.9, P = 0.034 after CT), and HGS measurements (27.5 ± 8.6 before, 26.8 ± 8.8 after CT, P = 0.007) have significantly decreased after CT. CC measurement < 31 cm at first visit was seen in 13.1% of patients, but the ratio raised to 20.3% after CT (χ², P = 0.003). Severe sarcopenia was determined in 33% of all patients, and 30.0% of them have been considered as sarcopenic obese., Conclusion: Sarcopenia and sarcopenic obesity were prevalent in this group patients. The CT caused a decrease in muscle functions, UMAC, and CC. Patients should be followed up carefully for sarcopenia, sarcopenic obesity, and nutritional aspect and it would be proper to intervene before sarcopenia has not occurred yet.

Background: Muscle function and its correlation with body composition and weight loss have not been studied deeply in pancreas and gastrointestinal cancers. This research aims to determine the skeletal muscle function and its relationship with body compartments, significant weight loss, and performance status (ECOG) 0-2 in a population with advanced digestive cancers., Methods: A cross-sectional study was designed to determine the relationship between muscular function, weight loss, and body composition. Patients with advanced digestive adenocarcinomas were evaluated. Muscle strength was examined by hand grip technique and body composition by bioimpedance analysis. Values of hemoglobin and albumin were measured in plasma., Results: A sample of 81 patients was included. They had adenocarcinoma of stomach (n = 9), pancreas (n = 28), or colorectum (n = 44). With regard to skeletal muscle function, sub-maximal strength increased when percentage of weight loss decreased (p = 0.002) or when any of the following variables increased: skeletal muscle (p < 0.001), waist-hip ratio (p < 0.001), body surface area (p < 0.001), and body mass index (p = 0.001). According to multivariate analysis of these variables, only percentage of weight loss and skeletal muscle remained statistically significant. Endurance had no correlation with any of the variables. Higher weight loss was found in tumors of the upper tract (stomach and pancreas) in comparison with those of the lower tract (colorectal) (p = 0.005)., Conclusions: In advanced digestive cancer, sub-maximal strength correlated inversely with weight loss and directly with skeletal muscle such as in lung and head and neck cancers. On the other hand, endurance had no correlation with any of the variables considered.

Symptoms of gastroenteropancreatic located neuroendocrine neoplasms (GEP-NENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs., Competing Interests: Conflict-of-interest statement: No conflict of interest.

Purpose: Dyspeptic symptoms present a severe problem in gastrointestinal (GI) cancer patients. The aim of the study was to analyze an association between gastric myoelectric activity changes and dyspeptic symptoms in gastrointestinal cancer patients., Material and Methods: The study included 80 patients (37 men and 43 women, mean age 61.2 ± 7.8 years) diagnosed with GI tract malignancies: colon (group A), rectal (group B) and gastric cancers (group C). Gastric myoelectric activity in a preprandial and postprandial state was determined by means of a 4-channel electrogastrography. Autonomic nervous system was studied based on heart rate variability analysis. The results were compared with the data from healthy asymptomatic controls., Results: In a fasted state, GI cancer patients presented with lesser percentages of normogastria time (A:44.23 vs. B:46.5 vs. C:47.10 vs. Control:78.2%) and average percentage slow wave coupling (ACSWC) (A:47.1 vs. B:50.8 vs. C:47.2 vs. Control:74.9%), and with higher values of dominant power (A:12.8 vs. B:11.7 vs. C:12.3 vs. Control:10.9) than the controls. Patients did not show an improvement in the percentage of normogastria time, dominant power, dominant frequency and ACSWC in response to food. The severity of dyspeptic symptoms correlated with the values of electrogastrography parameters. Patients showed lower values of heart rate variability parameters than the healthy controls, that indicate abnormal autonomic nervous system activity., Conclusion: GI cancers affect the gastric myoelectric activity, decreasing normogastria and slow wave coupling. These patients do not show adequate gastric motility response to food. Impaired gastric electric motility may result from cancer-induced autonomic disturbances., (Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

The aim of this study is to review sirolimus as a treatment for blue rubber bleb naevus syndrome (BRBNS). A literature search of Medline, Embase, CINAHL, SCOPUS and Google Scholar was conducted for publications reporting treatment of patients with BRBNS with sirolimus. Of 46 articles identified, 17 studies reporting 23 patients met inclusion criteria. Sirolimus was well tolerated in all but one patient who required treatment cessation; 17/18 patients noted an improvement in gastrointestinal disease where this was reported; 21/22 patients noted an improvement in cutaneous disease where this was reported. Based on these results, sirolimus may be considered a first-line treatment of BRBNS depending on patient morbidity., (© 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

To explore the relationship between fatigue and self-efficacy, and quality of life (QoL) during chemotherapy of patients with breast, lung or gastrointestinal cancers. This study is a descriptive-correlational research. The study population comprised of patients with breast, lung and gastrointestinal cancer treated at the outpatient chemotherapy unit. Patients' self-efficacy and QoL were assessed using Functional Assessment of Chronic Illness Therapy-Fatigue scale and Strategies Used by Patients to Promote Health scale. The sample included 236 patients receiving chemotherapy for lung cancer (30.9%), gastrointestinal (25.8%) or breast cancers (25.4%). The patients had little confidence in performing self-care self-efficacy during chemotherapy for the management of illness and chemotherapy-related side effects. The study found that the patients with cancer were moderately fatigued and all the domains of QoL of patients with cancer undergoing chemotherapy were considerably impaired. Positive correlations were found between self-efficacy scores and fatigue scores (p < 0.001), and QoL scores (p < 0.001). Better self-efficacy beliefs were associated with better QoL and lower fatigue. Improving the cancer patients' self-confidence in performing self-care behaviours may have a positive impact on performing cognitive and behavioural fatigue management strategies and can influence positively the patients' QoL during chemotherapy., (© 2018 John Wiley & Sons Ltd.)

Inflammasome signalling is an emerging pillar of innate immunity and has a central role in the regulation of gastrointestinal health and disease. Activation of the inflammasome complex mediates both the release of the pro-inflammatory cytokines IL-1β and IL-18 and the execution of a form of inflammatory cell death known as pyroptosis. In most cases, these mediators of inflammation provide protection against bacterial, viral and protozoal infections. However, unchecked inflammasome activities perpetuate chronic inflammation, which underpins the molecular and pathophysiological basis of gastritis, IBD, upper and lower gastrointestinal cancer, nonalcoholic fatty liver disease and obesity. Studies have also highlighted an inflammasome signature in the maintenance of gut microbiota and gut-brain homeostasis. Harnessing the immunomodulatory properties of the inflammasome could transform clinical practice in the treatment of acute and chronic gastrointestinal and extragastrointestinal diseases. This Review presents an overview of inflammasome biology in gastrointestinal health and disease and describes the value of experimental and pharmacological intervention in the treatment of inflammasome-associated clinical manifestations.

Background: Cancers of the upper gastrointestinal tract commonly result in malnutrition, which increases morbidity and mortality. Current nutrition best practice lacks a mechanism to provide early and intensive nutrition support to these patients. A 3-arm parallel randomised controlled trial is testing the provision of a tailored, nutritional counselling intervention delivered using a synchronous, telephone-based approach or an asynchronous, mobile application-based approach to address this problem. This protocol outlines the design and methods that will be used to undertake an evaluation of the implementation process, which is imperative for successful replication and dissemination., Methods: A concurrent triangulation mixed methods comparative analysis will be undertaken. The nutrition intervention will be provided using best practice behaviour change techniques and communicated either via telephone or via mHealth. The implementation outcomes that will be measured are: fidelity to the nutrition intervention protocol and to the delivery approach; engagement; acceptability and contextual factors. Qualitative data from recorded telephone consultations and written messages will be analysed through a coding matrix against the behaviour change techniques outlined in the standard operating procedure, and also thematically to determine barriers and enablers. Negative binomial regression will be used to test for predictive relationships between intervention components with health-related quality of life and nutrition outcomes. Post-intervention interviews with participants and health professionals will be thematically analysed to determine the acceptability of delivery approaches. NVivo 11 Pro software will be used to code for thematic analysis. STATA version 15 will be used to perform quantitative analysis., Discussion: The findings of this process evaluation will provide evidence of the core active ingredients that enable the implementation of best practice nutrition intervention for people with upper gastrointestinal cancer. Elucidation of the causal pathways of successful implementation and the important relationship to contextual delivery are anticipated. With this information, a strategy for sustained implementation across broader settings will be developed which impact the quality of life and nutritional status of individuals with upper gastrointestinal cancer., Trial Registration: 27th January 2017 Australian and New Zealand Clinical Trial Registry ( ACTRN12617000152325 ).

Background: Controlling nutritional status (CONUT) score has been reported to correlate with gastrointestinal (GI) cancer prognosis, but the results remain inconsistent. This study was to synthetically determine the associations between CONUT score and prognosis in GI cancers., Methods: Online databases PubMed, Web of Science, Cochrane library, Embase, Google scholar, Wanfang and National Knowledge Infrastructure (CNKI) were searched for eligible articles published prior to March 10, 2018. Pooled Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the prognostic potential of CONUT score in patients with GI cancers using Stata SE 12.0., Results: A total of 9 articles comprising 2400 patients were included in the analysis. Overall, CONUT score greater than the cutoff predicted poor 5-year overall survival for patients with GI cancers (HR = 2.39, 95% CI: 1.84-2.95, p < 0.001) and 5-year cancer-specific survival (HR: 3.47, 95% CI: 1.75-5.19, p < 0.001). And patients with high CONUT score were at significantly greater risk of relapse/recurrence (HR = 1.64, 95% CI: 1.30-1.98, p < 0.001)., Conclusion: CONUT could be a noninvasive prognostic indicator that useful for predicting long-term survival in GI cancer patients after surgery., (Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Cancer patients present various physiological, metabolic, social and emotional changes as a consequence of the disease's own catabolism, and may be potentiated in the gastrointestinal tract cancer by their interference with food intake, digestion and absorption., Aim: o evaluate the functionality of upper gastrointestinal cancer patients which have undertaken surgery and analyze the factors associated with changes in strength and functionality during hospitalization time., Methods: Prospective analytical study in patients with cancer of the upper gastrointestinal tract which have undertaken surgery. Was evaluated the handgrip strength using a hand dynamometer and functionality through the functional independence measure and Functional Status Scale for Intensive Care Unit in the preoperative period, 2nd and 7th postoperative day., Results: Were included 12 patients, 75% men, and mean age was 58.17 years old. The most prevalent tumor site was stomach (66.7%). There was a progressive reduction from the pre-operative palmar grip strength to the 2nd and 7th postoperative day, respectively. There was a decrease in functional performance from the preoperative period to the 2nd and a gain from the 2nd to the 7th postoperative day (p<0.001)., Conclusion: An important reduction in the handgrip strength and functionality was evidenced during the postoperative period in relation to the basal value in the pre-operative period.

Objective: The aims of this study were to examine the potential association between sleep problems, symptom burden, and survival in patients with advanced cancer., Methods: A prospective study of 294 patients with gastrointestinal cancer administered questionnaires assessing sleep, depression, anxiety, stress, pain, fatigue, and health-related quality of life. Serum levels of cytokines including interleukin (IL)-1α, IL-1β, tumor necrosis factor α, IL-10, IL-2, and interferon-γ were measured to assess biological mediation between sleep and survival. Survival was measured as time from diagnosis to death., Results: Fifty-nine percent of patients reported poor sleep quality, 53% reported poor sleep efficiency, 39% reported sleep latency greater than 30 minutes, and 45% reported sleeping less than 6 hours or greater than 10 hours. We found a significant association between sleep duration and symptom burden. Shorter sleep duration was significantly associated with higher levels of fatigue (r = -0.169, p = .01), pain (r = -0.302, p = .01), anxiety (r = -0.182, p = .01), depression (r = -0.172, p = .003), and lower levels of quality of life (r = 0.240, p = .01). After adjustment for demographic, psychological, and disease-specific factors, short sleep duration was associated with reduced survival (hazard ratio [HR] linear = 0.485, 95% confidence interval = 0.275-0.857) and there was also evidence for a quadratic pattern (HR quadrati = 1.064, 95% confidence interval = 1.015-1.115) suggesting a curvilinear relationship between sleep duration and survival. Interleukin 2 was the only cytokine significantly related to survival (HR = 1.01, p = .003) and sleep duration (β = -30.11, p = .027). When of IL-2 was added to the multivariable model, short and long sleep (β = -0.557, p = .097; β = 0.046, p = .114) were no longer significantly related to survival, suggesting mediation by IL-2., Conclusion: Sleep duration was associated with symptom burden and poorer survival and IL-2 was found to mediate the association between sleep and survival. Screening and treatment of sleep problems in patients diagnosed with cancer are warranted.