Is Preoperative Spirometry Necessary for Gastrointestinal Cancer Surgery?

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.

The Effect of Omega-3 Enriched Oral Nutrition Supplement on Nutritional Indices and Quality of Life in Gastrointestinal Cancer Patients: A Randomized Clinical Trial.

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.

Near-term prognostic impact of integrated muscle mass and function in upper gastrointestinal cancer.

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.

Bioelectrical Impedance Analysis and Mid-Upper Arm Muscle Circumference Can Be Used to Detect Low Muscle Mass in Clinical Practice.

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 CTPMI and both BIAFFMI (fat free mass index) (ICC 0.73), and BIAASMI (appendicular skeletal muscle index) (ICC 0.69) but not with MAMC (ICC 0.37). BIAFFMI (94%), BIAASMI (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.

Exploiting unique features of the gut-brain interface to combat gastrointestinal cancer.

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.

B Cell Lymphomas of the GI Tract.

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.

Heart Rate Variability as a Non-invasive Objective Parameter for Predicting the Occurrence of Chemotherapy-induced Peripheral Neuropathy in Patients With Gastrointestinal Cancer.

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.

Clinical Impact of Perioperative Oral Nutritional Treatment for Body Composition Changes in Gastrointestinal Cancer Treatment.

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.

Functional Impairments and Quality of Life in Older Adults With Upper Gastrointestinal Cancers.

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.

SARC-F has low correlation and reliability with skeletal muscle mass index in older gastrointestinal cancer patients.

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.

High protein diet improves the overall survival in older adults with advanced gastrointestinal cancer.

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.

Management of diet in gastrointestinal cancer.

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.

A non-lab nomogram of survival prediction in home hospice care patients with 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.

Usefulness of Preoperative Endoscopic Fluorescent Clip Marking in Laparoscopic Gastrointestinal Surgery.

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.

Melatonin and gastrointestinal cancers: Current evidence based on underlying signaling pathways.

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.

Neuroendocrine neoplasia of the gastrointestinal tract revisited: towards precision medicine.

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.

Glycemic variability in patients with gastrointestinal cancer: An integrative review.

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.

[Emerging roles of Hippo signaling pathway in gastrointestinal cancers and its molecular mechanisms].

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.

A high-protein diet, not isolated BCAA, is associated with skeletal muscle mass index in patients with gastrointestinal cancer.

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.

Widespread organ tolerance to Xist loss and X reactivation except under chronic stress in the gut.

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.