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Background: Patients with gastrointestinal cancer have a higher risk of malnutrition and postoperative infection., Objective: To investigate the nutritional status of patients with gastrointestinal cancers and factors for postoperative infections., Method: Based on the nutritional risk status, 294 patients with gastrointestinal tumours were divided into a nutritional risk group and a non-nutritional risk group, and the differences between the two groups were compared., Results: Among the included patients, 128 were at preoperative nutritional risk (43.54%); there were significant differences between the two groups in terms of age (66.25 ± 11.73 vs. 58.36 ± 10.41 years, P < 0.001), percentage of gastric cancers (39.84% vs. 28.92%, P = 0.049), percentage of stage IV tumours (60.16% vs. 45.18%, P = 0.011), total protein (64.90 ± 6.82 vs. 67.21 ± 7.41 g/L, P = 0.007), albumin (38.32 ± 4.74 vs. 41.61 ± 5.10 g/L, P < 0.001) and haemoglobin (112.72 ± 22.63 vs. 125.11 ± 22.79 g/L, P < 0.001). Multivariate logistic regression analysis showed that risk factors for postoperative infections in patients included age ≥ 60 years (odds ratio [OR] = 2.266 95%CI = 1.357-4.134), Nutrition Risk Screening (NRS)-2002 score ≥ 3 (OR = 2.183, 95%CI = 1.218-4.102), alcohol history (OR = 2.505, 95%CI = 1.370-4.683), comorbid diabetes mellitus (OR = 2.110, 95%CI = 1.381-4.023) and surgical time ≥ 6 h (OR = 2.446, 95%CI = 1.359-4.758)., Conclusion: Patients with gastrointestinal cancers are at high incidence of preoperative nutritional risk, and those with an NRS-2002 score of > 3, history of alcohol consumption and surgical time of > 6 h have a higher risk of postoperative infections., Competing Interests: Declarations Ethics approval and consent to participate This study was conducted in accordance with the Declaration of Helsinki and approved by the Research Ethics Committee of General hospital of TISCO (ethical batch number: K202406), and informed consent was obtained from all participants. All methods were carried out in accordance with relevant guidelines and regulations. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Clinical trial number Not applicable., (© 2024. The Author(s).)

Reversing cancer cachexia remains a challenge. Genetic biomarkers for the early detection of the disease have been explored in order to enable the implementation of preventive measures. We therefore genotyped candidate genes based on cachexia phenotype and quantified adiponectin and GDF-15 levels in cachectic patients with gastrointestinal cancer. Patients with a diagnosis of gastrointestinal cancer were divided into a cachectic and a non-cachectic group after the start of chemotherapy. A control group (no cancer) was also included. We genotyped the following single nucleotide polymorphisms (SNPs) by quantitative PCR: FOXO3 (rs1935949), FOXO3 (rs4946935), ACVR2B (rs2268757), and SELP (rs6136). In addition, we quantified adiponectin and GDF-15 levels by ELISA. The rs2268757 SNP in the ACVR2B gene was associated with the weight loss phenotype in cachectic patients with gastrointestinal cancer (non-cachectic, P = 0.004). Plasma adiponectin levels were higher in cachectic patients compared to controls (P = 0.01) and non-cachectic patients (P = 0.004). GDF-15 was also elevated in cachectic patients compared to controls (P < 0.0001) and non-cachectic patients (P = 0.001). Analysis by sex showed elevated adiponectin levels in men (control, P = 0.01) and cachectic women (control, P = 0.04; non-cachectic, P = 0.01), as well as elevated GDF-15 levels in men (control, P = 0.002) and cachectic women (control, P = 0.002; non-cachectic, P = 0.007). However, there was no significant difference in the levels of these cytokines between cachectic men and women. The results suggest the rs2268757 SNP in the ACVR2B gene, adiponectin, and GDF-15 as potential biomarkers of cachexia in gastrointestinal cancer., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Research Ethics Committee of the University of Ribeirão Preto (UNAERP) (protocol number 5.968.150), São Paulo, Brazil. Written informed consent was obtained from all participants in the study. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: While a large number of cases in an HIV setting may be attributed to infections, there has also been a rise in HIV- associated malignancies such as Kaposi sarcoma and aggressive B-cell lymphoma., Objective: To describe the clinicopathological features of cases with acute abdomen secondary to AIDS-defining malignancy in the gatrointestinal tract., Method: This is a retrospective analysis of all cases presenting with acute abdomen and histologically diagnosed AIDS-defining malignancies of the gastrointestinal tract over a period of 8 years in our centre. Clinicopathological characteristics were retrieved from the laboratory information system. Archived haematoxylin and eosin-stained sections and immunohistochemical stains were reap- praised., Results: A total of 13 cases, which consisted of 5 males and 8 females, with an average age of 35 years formed the study sample. All the patients were HIV-positive on antiretroviral therapy, and presented with acute abdomen. Intraoperatively, there were five intussusceptions, three strictures, three perforated tumours and two luminal occlusions. Histopathology confirmed five cases of Kaposi sarcoma and eight cases of high-grade B-cell lymphomas. Two patients with high-grade B-cell lymphomas died after surgical intervention., Conclusion: Expedited histopathological assessment of bowel resection in HIV-infected patients could improve clinical outcomes with early treatment.

Objective: The study aimed to develop a model to predict the risk of sarcopenia in gastrointestinal cancer patients. The goal was to identify these patients early and classify them into different risk categories based on their likelihood of developing sarcopenia., Methods: This study evaluated risk factors for sarcopenia in patients with gastrointestinal cancers through a systematic review and meta-analysis. The natural logarithm of the combined risk estimate for each factor was used as a coefficient to assign scores within the model for risk prediction. Data from 270 patients with gastrointestinal cancers, collected between October 2023 and April 2024, was used to assess the predictive performance of the scoring model., Results: The analysis included 17 studies that included 9405 patients with gastrointestinal cancers, out of which 4361 had sarcopenia. The model identified several significant predictors of sarcopenia, including age (OR = 2.45), sex (OR = 1.15), combined diabetes (OR = 2.02), neutrophil-to-lymphocyte ratio (NLR) category (OR = 1.61), TNM stage (OR = 1.61), and weight change (OR = 1.60). Model validation was performed using an external cohort through logistic regression, resulting in an area under the curve (AUC) of 0.773. This model attained a sensitivity of 0.714 and a specificity of 0.688 and ultimately selected 16.5 as the ideal critical risk score. Furthermore, an AUC of 0.770 was obtained from Bayesian model validation; the optimal critical risk score was determined to be 19.0, which corresponds to a sensitivity of 0.658 and a specificity of 0.847., Conclusions: The model of risk prediction developed through systematic review and meta-analysis demonstrates substantial for sarcopenia in patients with gastrointestinal cancers. Its clinical usability facilitates the screening of patients at high risk for sarcopenia., Competing Interests: Conflict of Interest statement All authors do not have conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: TC-325 powder has been successfully used in the management of malignancy-related upper gastrointestinal bleeding (UGIB) with favorable results. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing TC-325 hemostatic powder with standard endoscopic treatments in the management of malignancy-related UGIB., Methods: Several databases were reviewed from inception to May 02, 2024 to identify RCTs comparing TC-325 and standard endoscopic treatments for the management of malignancy-related UGIB. Our outcomes of interest were immediate hemostasis, 30-day rebleeding, length of hospital stay, need for surgery, need for angiographic embolization, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for categorical variables and mean difference (MD) with 95% CI for continuous variables. We used a random effect model to analyze the data and heterogeneity was assessed by I 2 statistic., Results: Four RCTs with 227 patients were included. We found that, the rate of immediate hemostasis was significantly higher in the TC-325 group compared to the standard therapy group, RR (95% CI): 1.48 (1.26, 1.74). There was no significant difference in 30-day rebleeding between the groups RR (95% CI): 0.52 (0.15, 1.76). We found no significant difference in other outcomes between groups such as the need for angiographic embolization, all-cause mortality, length of hospital stay, and need for surgery., Conclusions: We found that, TC-325 hemostatic powder was superior to standard endoscopic treatments in achieving immediate hemostasis in patients with malignancy-related UGIB., Competing Interests: Declarations Conflict of interest The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Malignant bowel obstruction (MBO) due to peritoneal carcinomatosis (PC) is associated with poor outcomes. Optimal management for palliation remains unclear. This study aims to characterize nonoperative, procedural, and operative management strategies for MBO and evaluate its association with mortality and cost. Materials and Methods: ICD-10 coding identified patient admissions from the 2018 to 2019 National Inpatient Sample (NIS) for MBO with PC from gastrointestinal or ovarian primary cancers. Management was categorized as nonoperative, procedural, or surgical. Multivariate analysis was used to associate treatment with mortality and cost. Results: 356,316 patient admissions were identified, with a mean age of 63 years. Gender, race, and insurance status were similar among groups. Length of stay (LOS) was longest in the surgical group (surgical: 17 days; procedural: 14 days; nonoperative: 7 days; P = .001). In comparison to nonoperative, procedural and surgical patients had statistically higher hospital charges, post-discharge medical needs, palliative care consults, and admission to rehab centers. Mortality was 7% in nonoperative, 9% in procedural, and 8% in surgical ( P = .007) groups. In adjusted analyses, older age, palliative care consult, and non-Medicare payer status were associated with higher mortality. Compared to nonoperative, procedural and surgical groups resulted in increased costs (procedural: $17K more; surgical: $30K more). Conclusions: Admissions for procedural and surgical treatment of MBO are associated with increased LOS, hospital costs, and discharge needs. Optimal management remains challenging. Clinicians must examine all options prior to recommending palliative interventions given a trend towards higher resource utilization and mortality., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a significant and ever-increasing health and economic burden worldwide. Substantial epidemiological evidence shows that MASLD is a multisystem disease that is associated not only with liver-related complications but is also associated with an increased risk of developing cardiometabolic comorbidities and extrahepatic cancers (principally gastrointestinal [GI] cancers). GI cancers account for a quarter of the global cancer incidence and a third of cancer-related deaths. In this narrative review, we provide an overview of the literature on (a) the epidemiological data on the risk of non-liver GI cancers in MASLD, (b) the putative mechanisms by which MASLD (and factors linked with MASLD) may increase this risk, and (c) the possible pharmacotherapies beneficially affecting both MASLD and extrahepatic GI cancer risk. There are multiple potential pathophysiological mechanisms by which MASLD may increase extrahepatic GI cancer risk. Although further studies are needed, the current evidence supports a possible extrahepatic carcinogenic role for MASLD, regardless of obesity and diabetes status, thus highlighting the potential role of tailoring cancer screening for individuals with MASLD. Although there are conflicting data in the literature, aspirin, statins and metformin appear to exert some chemo-preventive effects against GI cancer., Competing Interests: Declaration of competing interest The Authors have no potential conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rationale: Trousseau syndrome (TS) is a thrombosis disorder characterized by a hypercoagulable state linked to underlying malignancies, resulting in various thrombotic events such as deep vein thrombosis, pulmonary embolism, and arterial thrombosis. This syndrome serves as a crucial indicator of malignancy and can often be the first sign of an underlying tumor. In this case, we report a case of gastrointestinal malignant tumor as the first onset, and analyzes its clinical characteristics to improve the clinicians' understanding of this kind of disease., Patient Concerns: A 69-year-old woman was admitted to the hospital 4 times in 1 month for cerebral infarction. The patient was admitted several times with a new cerebral infarction lesion and a high D-dimer level, a persistently positive fecal occult blood test, and a gastrointestinal tumor was later found., Diagnosis: The patient was diagnosed with TS, attributed to her underlying malignancy., Interventions: During hospitalization, the patients were treated with aspirin for antiplatelet, esomeprazole for protection of gastric mucosa, atorvastatin for lowering blood lipids, butylphthalein for improvement of collateral circulation, edaravone dextrocamphorol for scavenging oxygen free radicals, and betahistine hydrochloride tablets for preventing dizziness., Outcomes: The patient's condition improved significantly after initial treatment, but died of the tumor a year after discharge., Lessons: Currently, TS has a complex and varied clinical presentation and is relatively difficult to diagnose, especially in patients with an unknown tumor history. Focus should be placed on patients with recurrent cerebral infarctions and increased D-dimer levels, and anticoagulation may be an effective treatment for patients with TS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Gastrointestinal tumors, including those of the stomach, colon, rectum, and esophagus, present significant global health challenges. Chemotherapy, essential for treating these cancers, often causes constipation, adversely affecting patients' quality of life. This study examines the mechanisms behind chemotherapy-induced constipation, such as the direct impact of chemotherapeutic drugs on intestinal function, reduced fluid intake, decreased physical activity, opioid use, and psychological stress. While traditional treatments like stimulant and osmotic laxatives are commonly used, emerging therapies such as 5-HT4 receptor agonists and probiotics show promise. Traditional Chinese medicine offers additional strategies with herbal remedies and dietary adjustments. Future research should prioritize precision medicine, combining pharmacological and non-pharmacological approaches, and developing innovative therapeutics utilizing biologics and nanotechnology. Ongoing research is crucial for improving chemotherapy-induced constipation management, aiming to enhance treatment outcomes and the quality of life for chemotherapy patients with gastrointestinal tumors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The study aimed to determine the nutritional status and its prognostic effect on the survival of patients with advanced gastrointestinal cancer., Methods: A prospective cohort study design was conducted in a tertiary hospital in Shanghai, China. The study consisted of 202 advanced gastrointestinal (GI) cancer patients from a palliative care unit. The following data were collected from the patients: biochemical indicators, i.e., anemia (hemoglobin levels), albumin, pre-albumin, C-reactive protein (CRP), and anthropometric parameters, i.e., body mass index (BMI), nutritional status by Patient-Generated Subjective Global Assessment (PG-SGA), and performance status by Karnofsky Performance Status (KPS). Severe malnutrition was confirmed with the PG-SGA score of ≥ 9. Kaplan-Meier survival analysis and the log-rank test were used to calculate overall survival (OS). The effect of nutritional status on survival was performed by Cox regression analysis., Results: Severe malnutrition was found in 71.3% of patients according to the cutoff of the PG-SGA. PG-SGA score ≥ 9, albumin level < 35 g/L, and CRP level ≥ 10 mg/L predicted shortened life expectancy. Multivariate Cox regression analysis results showed that the PG-SGA score ≥ 9 and the albumin level < 35 g/L were predictive of OS., Conclusion: Our data support that severe malnutrition is a predictor for OS in patients with advanced GI cancer. Information on nutritional status should be considered to individualize palliative care plan for these patients, and hence improve their quality of life., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Malignant bowel obstruction (MBO) is a common complication of patients with advanced malignancies and has poor prognosis. Currently, there are limited guidelines for MBO management or predicting outcomes for these patients., Objective: To identify patient factors associated with readmission and mortality after hospital admission for MBO., Participants: A 5-year retrospective review was performed from 2017 to 2022 at a single tertiary institution to evaluate patients admitted for MBO. All patients had advanced cancer of gastrointestinal or gynecologic primary. Patient demographics, socioeconomic factors, tumor characteristics, and inpatient outcomes were collected. Multivariable analyses were performed to determine variables predicting hospital readmission for recurrent MBO and 90-day mortality., Results: 210 patients were included. Mean age was 61 years, 28% were male, and 19% did not primarily speak English. 35% of patients lived over 50 miles from the hospital. On multivariable analysis, non-English speaking patients exhibited increased risk of readmission for MBO (OR = 2.82, P = .039). Older age was associated with decreased risk for MBO readmission (OR = .96, P = .007). Ascites was associated with increased mortality (OR = 2.17, P = .043). Earlier palliative care (PC) consultation predicted decreased readmission (OR = .24, P < .001) yet increased mortality at 90 days (OR = 3.20, P = .003)., Conclusion: Patient age, primary language, and PC consult were predictors for MBO readmission, which may impact 90-day mortality. Given the palliative nature of MBO, modifiable factors such as PC consultation and multidisciplinary goals of care discussions should be prioritized in order to reduce readmissions and focus on quality of life (QOL) for this patient population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This research aimed to develop and validate a clinical nomogram for predicting the probability of cardiovascular death (CVD) in patients with gastrointestinal stromal tumors (GIST). Information regarding patients diagnosed with GIST was extracted from the surveillance, epidemiology, and end results database. The multivariable competing risk model and multivariable Cox regression model were utilized to determine the independent predictive factors. A comparison was made between the results obtained from the 2 models. A nomogram was built to visualize the competing risk model. The nomogram's performance was assessed utilizing concordance index, calibrate curve, decision curve analysis, and risk stratification. A total of 9028 cases were enrolled for final analysis, with CVD accounting for 12.8% of all deaths since GIST diagnosis. The multivariate analysis of competing risks revealed that age, chemotherapy and marital status were identified as independent risk factors for CVD in GIST individuals. The nomogram model exhibited good calibration and strong discriminative ability, indicating its effectiveness in predicting outcomes, with a concordance index of 0.788 (95% confidence interval: 0.753-0.823) in the training set, and 0.744 (95% confidence interval: 0.673-0.815) in the validation set. Decision curve analysis indicated that the prediction model had good clinical practicability. Additionally, risk stratification analysis efficiently divided GIST individuals into high- and low-risk populations for CVD. This was the first research to construct and validate a predictive nomogram using a competing risk model to estimate the individual probabilities of CVD in GIST patients. The nomogram can assist clinicians in making personalized treatment and monitoring plans., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Older adults comprise the majority of patients with gastrointestinal (GI) cancer. Geriatric assessments (GAs) are recommended for older adults with cancer in part to detect aging-related impairments (e.g., frailty) associated with early mortality. Social factors like social vulnerability may also influence aging-related impairments. However, the association between social vulnerability and aging outcomes among older adults with cancer is understudied., Methods: The authors included 908 older adults aged 60 years and older who were recently diagnosed with GI cancer undergoing GA at their first prechemotherapy visit to the University of Alabama at Birmingham oncology clinic. The primary exposure of interest was the social vulnerability index (SVI). Outcomes were frailty (frail vs. robust/prefrail) and total number of GA impairments (range, 0-13). The authors examined the association between SVI and outcomes using Poisson regression with robust variance estimation and generalized estimating equations., Results: The median age at GA was 69 years (interquartile range, 64-75 years), 58.2% of patients were male, 22.6% were non-Hispanic Black, 29.1% had colorectal cancer, 28.2% had pancreatic cancer, and 70.3% had stage III/IV disease. Adjusting for age, sex, cancer type, and disease stage, each decile increase in the SVI was associated with an 8% higher prevalence of frailty (prevalence ratio, 1.08; 95% confidence interval, 1.05-1.11) and a 4% higher average count of total GA impairments (risk ratio, 1.04; 95% confidence interval, 1.02-1.06). The results were attenuated after further adjustment for race and education., Conclusions: Greater social vulnerability was associated with a higher prevalence of frailty and an increasing average number of GA impairments among older adults with GI cancers before systemic treatment. Intervening on social vulnerability may be a target for improving the risk of frailty and GA impairments, but associations of race and education should be further evaluated., (© 2024 The Author(s). Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: The cachexia index is a novel biomarker of cancer cachexia. This systematic review and meta-analysis aimed to evaluate the prognostic impact of cachexia index on prognosis after surgery for gastrointestinal cancer., Methods: In August 2023, we systematically searched PubMed, the Cochrane Library, and Ovid for relevant studies on the oncological outcome after gastrointestinal cancer surgery and analyzed the findings from these studies for meta-analysis., Results: Our systematic and meta-analysis review identified eight studies involving 1876 patients. The number of patients with low cachexia index accounted for 813 patients (43.3%). We found that low cachexia index was associated with worse overall survival (pooled HR, 2.30; 95% CI, 1.85-2.87; z = 7.49; P < 0.001) and disease/relapse/progression-free survival (pooled HR, 1.77; 95% CI, 1.45-2.18; z = 5.50; P < 0.001)., Conclusion: Our meta-analysis showed that cachexia index was associated with oncological outcome after gastrointestinal cancer surgery. However, the limitations of this meta-analysis should be taken into consideration when interpreting the results., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The aim of this study was to investigate the relationship among phase angle (PA), malnutrition, and prognosis in patients with gastrointestinal cancer., Methods: In total, 870 patients with gastrointestinal cancer were enrolled. Kaplan-Meier curves and Cox proportional hazards models were used to evaluate the association between PA and survival risk. Restricted cubic spline regression was used for flexibility analysis to explore sex-specific associations between PA and survival. Logistic regression was used to assess the relationships among PA, malnutrition, and cachexia., Results: Low PA was closely associated with poor physical conditions, diminished quality of life, and malnutrition. Patients with low PA had a significantly worse prognosis than those with high PA (60.6% versus 72.8%; log-rank P < 0.001). PA was suitable for the prognostic assessment of patients with advanced-stage tumors. Regardless of sex, patients with lower PA showed significantly poorer survival rates. Cox proportional hazards models identified PA as an independent predictor of prognosis in patients with gastrointestinal cancer (hazard ratio (HR)=0.534; 95% confidence interval (CI)=0.409-0.696, P < 0.001). Subgroup analysis indicated that a high PA was an independent risk factor affecting the prognoses of patients with esophageal, liver, and intrahepatic bile duct cancers. Interestingly, variations in PA had a more significant prognostic effect on survival in men than in women. The logistic regression model confirmed that PA is a valuable indicator for assessing malnutrition and cachexia in patients with gastrointestinal cancer. Among all body composition indicators, PA demonstrated the highest accuracy for prognostic prediction., Conclusions: PA was identified as a robust predictor of malnutrition and poor prognosis in patients with gastrointestinal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Aims: We investigated the benefit-risk profile of aspirin on mortality reduction from chemoprevention of gastrointestinal (GI) cancer vs excess mortality from bleeding among Helicobacter pylori-eradicated patients, and its interaction with proton pump inhibitors (PPIs)., Methods: H pylori-eradicated patients (between 2003 and 2016), identified from a territory-wide database, were observed from the date of H pylori therapy until death or the end of the study (July 2020). Primary exposure was aspirin use as time-varying variable. The primary outcome was GI cancer-related (gastrointestinal, hepatobiliary, or pancreatic cancer) death and the secondary outcome was bleeding-related (gastrointestinal bleeding or intracranial bleeding) death. The adjusted hazard ratio (aHR) of outcomes was calculated by multivariable Cox model after adjusting for age, sex, comorbidities, and concomitant medications. The benefit-risk profile was expressed as the adjusted absolute risk difference of cancer-related deaths and bleeding-related deaths between aspirin users and nonusers., Results: A total of 87,967 subjects were followed up for a median of 10.1 years, with 1294 (1.5%) GI cancer-related deaths and 304 (0.3%) bleeding-related deaths. Aspirin was associated with lower GI cancer-related mortality (aHR, 0.51; 95% CI, 0.42-0.61), but higher bleeding-related mortality (aHR, 1.52; 95% CI, 1.11-2.08). Among PPI users, the aHR of bleeding-related mortality with aspirin was 1.06 (95% CI, 0.70-1.63). For the whole cohort, the adjusted absolute risk difference between aspirin users and nonusers was 7 (95% CI, 5-8) fewer cancer-related and 1 (95% CI, 0.3-3) more bleeding-related death per 10,000 person-years. Among concomitant PPI-aspirin use, there were 9 (95% CI, 8-10) fewer cancer-related deaths per 10,000 person-years without an increase in bleeding-related deaths., Conclusions: GI cancer mortality benefit from aspirin outweighs bleeding-related mortality in H pylori-eradicated subjects, which is enhanced further by PPI use., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Direct oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer., Methods: Using the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N = 88; lower GI cancer: N = 114; non-GI cancer: N = 947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model., Results: The upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4 %, lower GI cancer: 15.4 %, and non-GI cancer: 11.6 %, P = 0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53 %), followed by the lower GI (24 %). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95 %CI, 1.31-3.87, P = 0.003), but that in lower GI cancer was insignificant., Conclusions: Upper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816., Competing Interests: Declaration of competing interest Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Morimoto reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Dr. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi Sankyo. All other authors declare that they have no conflict of interest., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Introduction: Gastrointestinal (GI) bleeding stemming from malignant tumors is increasingly recognized, due to advancements in oncology and detection methods. Traditional endoscopic hemostatic techniques have shown variable success rates in managing hemorrhagic GI neoplasms. Hemospray, an emerging endoscopic hemostatic powder, offers promise in treating upper GI bleeding, potentially extending its utility to neoplastic bleeding sites. This meta-analysis aims to evaluate Hemospray's efficacy in managing bleeding related to GI tumors., Methods: We searched Embase, Scopus, Web of Science, Medline/PubMed, and Cochrane. Inclusion criteria encompassed studies focusing on malignancy-related GI bleeding and interventions utilizing Hemospray. Comparative studies contrasted Hemospray with standard endoscopic treatments (SET), while noncomparative studies assessed Hemospray's efficacy independently. The risk of bias was assessed using appropriate tools, and statistical analyses were performed using Review Manager and open Meta analyst software., Results: We included 19 studies in our meta-analysis. Hemospray demonstrated higher rates of immediate hemostasis compared to SET (odds ratio: 17.14, 95% confidence interval: 4.27-68.86), with consistent outcomes across studies. Rebleeding rates at 14 and 30 days were comparable between Hemospray and SET groups, suggesting similar efficacy in long-term hemostasis. Hemospray showed a significantly lower need for nonendoscopic hemostasis compared to SET (odds ratio: 0.51, 95% confidence interval: 0.30-0.87), indicating a potential reduction in supplementary interventions. Safety assessments revealed no confirmed adverse events directly linked to Hemospray., Conclusion: This meta-analysis highlights Hemospray's efficacy in achieving immediate hemostasis in GI tumor-related bleeding, with potential benefits in reducing supplementary interventions and improving patient outcomes. Despite comparable rebleeding rates, Hemospray emerges as a valuable adjunctive therapy in managing malignant GI bleeding., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Periodontitis can disrupt oral and gut microbiota, leading to dysbiosis that affects overall systemic health. Besides the spread of periodontal pathogens by the hematogenous route, they can also be translocated into the gastrointestinal tract, possibly intervening in the neoplastic process in the gastrointestinal tract. This manuscript reviews the relationship between oral and gut microbiota due to periodontitis, discussing systemic health implications and potential links to gastrointestinal cancer. This article highlights the significance and effect of dysbiosis in the gut, emphasizing the importance of maintaining oral health to prevent systemic diseases. Lastly, it will go through therapeutic innovations such as probiotics and oral microbiota analysis tools for systemic disease detection. These findings will mark the integration of oral health management in clinical practice to lower systemic disease risk and improve overall patient outcomes. Aim of work : This manuscript aims to unravel the pathological interaction between oral and gut microbiota and their bidirectional effect on systemic diseases. Materials and methods : The review was performed using the MEDLINE and ScienceDirect databases. Reviewed articles were published in English between the year 2015 and 2024. The search used keywords such as ("oral microbiota" AND "periodontal disease") OR ("oral microbiota" AND "gastrointestinal cancer") OR ("Porphyromonas gingivalis" AND "periodontal disease") OR ("Helicobacter pylori" AND "gastric cancer") OR ("gut microbiome" AND "inflammatory bowel disease") OR ("oral microbiome" AND "systemic diseases"). Conclusions : The dysbiotic change in the oral cavity due to periodontitis is linked directly and indirectly to systemic diseases such as IBS, neurodegenerative diseases, muscle joint diseases, respiratory infections, and gastrointestinal cancer; this underscores the importance of maintaining oral hygiene for prophylaxis of oral diseases and the prevention of systemic diseases. A better understanding of the interconnections between oral health and systemic diseases will integrate oral health management to offer new prevention, diagnostic, and treatment opportunities to improve overall patient outcomes.

Background: Cancer cachexia is characterized by the loss of body weight (BW) and anorexia. Anamorelin (ANAM) is a selective ghrelin receptor agonist with appetite-enhancing anabolic action. The ONO-7643-05 trial demonstrated that ANAM increased lean body mass and improved anorexia in a Japanese population. However, the clinical outcomes of patients on ANAM have not yet been reported., Patients and Methods: We investigated the clinical outcomes of patients with unresectable, advanced, or recurrent gastrointestinal cancer (colorectal, gastric, or pancreatic cancer) who were treated with ANAM between April 2017 and August 2022. Cachexia was defined as the presence of anorexia and a loss of ≥ 5% of BW within 6 months. To evaluate the response to ANAM, the patients who had discontinued ANAM within 3 weeks were excluded. Response to ANAM was defined as maintenance of or increase in BW and improved appetite from baseline at every 3-week evaluation. We also collected data on the reasons for the discontinuation of ANAM and the correlation between clinical factors and ANAM response. Safety analysis of ANAM was performed for all patients who received ANAM., Results: Seventy-four patients were included in this study (49 males and 25 females), with a median age of 67.1 years (range, 36-83). The primary tumors were colorectal cancer in 27 (36.5%), gastric cancer in 20 (27.0%), and pancreatic cancer in 27 (36.5%). The Eastern Cooperative Oncology Group performance status was 0 in 10 (13.5%), 1 in 44 (59.5%), and ≥ 2 in 20 (27.0%). The number of previous chemotherapy regimens was 0 in 20 (27.0%), 1 in 22 (29.7%), and ≥ 2 in 32 (43.2%). ANAM was discontinued within 3 weeks in 28 patients for the following reasons: low-grade (grade 1 or 2) adverse events in 15 patients, ileus in three, grade 3 fatigue in one, progressive disease in one, censored follow-up in six, and unknown reasons in three. The proportion of ANAM responders was 63.6% (95% confidence interval, 47.8-77.6%). Among baseline characteristics, age ≥ 75 attenuated the ANAM response (p = 0.03). ANAM responders showed better disease control with chemotherapy than non-responders (75.0% vs. 37.5%, p = 0.02)., Conclusions: ANAM may improve the outcomes of patients with gastrointestinal cancer cachexia in clinical practice., (© 2024. The Author(s).)

Objective: This study aimed to compare the effects of patient-controlled intravenous analgesia (PCIA) with and without low-basal infusion on postoperative hypoxaemia., Design: A randomised parallel-group non-inferiority trial., Setting: The trial was conducted at a grade-A tertiary hospital from December 2021 to August 2022., Participants: 160 adults undergoing gastrointestinal tumour surgery and receiving postoperative PCIA., Interventions: Participants randomly received a low-basal (0.1 mg/hour of hydromorphone) or no-basal infusion PCIA for postoperative 48 hours., Primary and Secondary Outcome Measures: Primary outcome was area under curve (AUC) per hour for hypoxaemia, defined as pulse oxygen saturation (SpO 2 ) <95%. Secondary outcomes included: AUC per hour at SpO 2 <90% and <85%, hydromorphone consumption, ambulation time and analgesic outcomes up to 48 hours after surgery., Results: Among 160 randomised patients, 159 completed the trial. An intention-to-treat analysis showed that AUC per hour (SpO 2 <95%) was greater in the low-basal infusion group compared with the no-basal infusion group, with a median difference of 0.097 (95% CI 0.001 to 0.245). Non-inferiority (margin: ratio of means (ROM) of 1.25) was not confirmed since the ROM between the two groups was 2.146 (95% CI 2.138 to 2.155). Hydromorphone consumption was higher in the low-basal group than in the no-basal group (median: 5.2 mg versus 1.6 mg, p<0.001). Meanwhile, there were no differences in the AUC values at the other two hypoxaemia thresholds, in ambulation time, or pain scores between the groups., Conclusions: Among the patients receiving hydromorphone PCIA after gastrointestinal tumour resection, low-basal infusion was inferior to no-basal infusion PCIA for postoperative hypoxaemia at SpO 2 <95% up to 48 hours after surgery., Trial Registration Number: ChiCTR2100054317., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Neuroendocrine neoplasms (NENs) are slow-growing tumors. Sarcopenia is defined as the loss of muscle mass, strength, and physical performance. First-line NEN therapy is somatostatin analogs, which could be responsible for malabsorption conditions, such as pancreatic exocrine insufficiency (EPI) with underlying sarcopenia., Aim: Evaluate the prevalence of sarcopenia in patients with NENs at diagnosis and during follow-up., Methods: A retrospective single-center study was conducted, including patients with advanced intestinal NENs G1/G2 (excluded pancreatic NENs). CT scans were analyzed at diagnosis and after 6 months of therapy, and the skeletal muscle index was assessed., Results: A total of 30 patients (F:M = 6:24) were enrolled, with the following primary tumor sites: 25 in the ileum, 1 stomach, 2 jejunum, and 2 duodenum. At diagnosis, 20 patients (66.6%) showed sarcopenic SMI values, and 10 patients (33.3%) showed non-sarcopenic SMI values. At follow-up, three more patients developed sarcopenic SMI values. Statistical significance in relation to the presence of sarcopenia was found in the group of patients with carcinoid syndrome ( p = 0.0178), EPI ( p = 0.0018), and weight loss ( p = 0.0001)., Conclusion: Sarcopenia was present in 2/3 of the patients with advanced intestinal NENs at the diagnosis and during the follow-up. It is reasonable to consider this condition to improve clinical outcomes.

Competing Interests: Declaration of Competing Interest None.

Background: Sarcopenic obesity (SO) in patients with gastrointestinal cancer is associated with a poor prognosis. We aimed to investigate the prognostic impact of SO in patients with gastrointestinal cancer, as well as the diagnostic cut-off value of SO in patients with gastrointestinal cancer among Chinese population., Methods: We conducted a consecutive cohort study. Between January 2017 and January 2019, 289 patients diagnosed with gastrointestinal cancer were included in our study. Skeletal muscle area, total fat area, and subcutaneous fat area were measured by CT scan. All patients were followed up for 5 years. Receiver operating characteristic curves (ROC) were adopted to determine the cut-off values of visceral fat obesity for the prediction of sarcopenia. Based on the cut-off values, patients with sarcopenia combined with visceral fat obesity were divided into the SO group, and the others were divided into the non-sarcopenic obesity (NSO) group. Kaplan-Meier curves and univariate and multivariate Cox proportional hazard models were employed to explore the associations of body composition profiles with 5-year overall survival and disease-specific survival., Results: Obtained from Youden's Index for ROC for the prediction of 5-year survival, skeletal muscle mass index (SMI) ≤40.02 cm 2 /m 2 with VFA ≥ 126.30 cm 2 in men and SMI ≤32.05 cm 2 /m 2 with VFA ≥72.42 cm 2 in women indicate a risk of poor prognosis in patients diagnosed with gastrointestinal cancer. Patients with SO had poorer 5-year overall survival (OS) than patients with NSO (6.74% vs. 82.84%, p < 0.001), and poorer 5-year DFS (6.74% vs. 81.82%, p < 0.001). In multivariate analysis, we found that the long-term mortality risk was approximately 13-fold higher among patients in the SO group compared to those with no conditions., Conclusions: Preoperative assessment of SO is useful not only for monitoring nutritional status but also for predicting 5-year OS in gastrointestinal cancer patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: We sought to assess healthcare utilization and expenditures among patients who developed venous thromboembolism (VTE) after gastrointestinal cancer surgery., Methods: Patients who underwent surgery for esophageal, gastric, hepatic, biliary duct, pancreatic, and colorectal cancer between 2013 and 2020 were identified using the MarketScan database. Entropy balancing was performed to obtain a cohort that was well balanced relative to different clinical covariates. Generalized linear models were used to compare 1-year postdischarge costs among patients who did and did not develop a postoperative VTE., Results: Among 20,253 individuals in the analytical cohort (esophagus [n = 518 {2.6%}], stomach [n = 970 {4.8%}], liver [n = 608 {3.0%}], bile duct [n = 294 {1.5%}], pancreas [n = 1511 {7.5%}], colon [n = 12,222 {60.3%}], and rectum [n = 4130 {20.4%}]), 894 (4.4%) developed VTE. Overall, most patients were male (n = 10,656 [52.6%]), aged between 55 and 64 years (n = 10,372 [51.2%]), and were employed full time (n = 11,408 [56.3%]). On multivariable analysis, VTE was associated with higher inpatient (mean difference [MD], $17,547; 95% CI, $15,141-$19,952), outpatient (MD, $8769; 95% CI, $7045-$10,491), and pharmacy (MD, $2811; 95% CI, $2509-$3113) expenditures (all P < .001). Furthermore, patients who developed VTE had higher out-of-pocket costs for inpatient (MD, $159; 95% CI, $66-$253) and pharmacy (MD, $122; 95% CI, $109-$136) services (all P < .001)., Conclusion: Among privately insured patients aged <65 years, VTE was associated with increased healthcare utilization and expenditures during the first year after discharge., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status., Methods: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method., Results: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer)., Conclusions: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer., Competing Interests: Declaration of competing interest The authors report the following relationships unrelated to this study. NN reports speaker fees from Bayer and AstraZeneca. CFA reports research grants from The Danish Heart Foundation, Toyota Foundation, Aase & Ejnar Danielsen's Foundation, Arvid Nilsson's Foundation, The Research and Innovation Foundation of the Department of Cardiology, Herlev and Gentofte University Hospital, Fru Asta Florida Bolding's Memorial Grant and the KV Foundation; support for attending meetings from AstraZeneca and European Heart Foundation Association. ML reports research grants from Karen Elise Jensen Fonden, Danish Heart Foundation, Bayer, and BMS; speaker fees from BMS, Pfizer, Bayer and Astra Zeneca; and advisory board positions with Pfizer and Astra Zeneca. MS reports speaker fees from Novartis, Boehringer Ingelheim, Bayer, Novo, and Astra Zeneca. ELG research grants from Boehringer Ingelheim; speaker fees from Pfizer, Bayer, AstraZeneca and Bristol Myers-Squibb; consulting fees from Bayer, Bristol Myers-Squibb, MSD and Boehringer Ingelheim. AH, JES, SKN, CS, DN and JT report no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Access to new endoscopic treatment modalities often depends on price. To resolve this gap and therefore help to ensure that care delivery can occur on a clinical basis, we aimed to establish the value to insurers of novel hemostatic powder to treat GI tumor bleeding., Methods: A decision-analytic model developed to assess the impact of endoscopic intervention on the risk of 30-day readmission for GI bleeding from an insurer perspective was adapted to assess GI tumor bleeding with hemostatic powder or standard endoscopic therapy. Costs were derived from Medicare populations. Outcomes were derived from a recent multicenter randomized clinical trial., Results: Costs ranged from $651 to $1613 to treat upper GI tumor bleeding and from $531 to $1014 to treat lower GI tumor bleeding based on risk reduction in 30-day hospital readmission for recurrent bleeding. These valuations should represent medical device and incremental facility costs in addition to incremental physician and staff time., Conclusions: Coverage for novel endoscopic hemostatic powder therapy seems cost-saving to insurers., Competing Interests: Disclosure The following authors disclosed financial relationships: R. Law: consultant for Boston Scientific, Medtronic, and Conmed; research support from Olympus America, Boston Scientific, and WL Gore; and royalties from UpToDate. E.D. Shah: consultant for Cook outside of the scope of this work, and for Ardelyx, Mahana, Mylan, Neuraxis, Salix, Sanofi, and Takeda. Dr Shah is supported by a grant from the National Institutes of Health (K23DK134752)., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Gastrointestinal tumors bleeding remains a significantly clinical challenge due to its resistance to conventional endoscopic hemostasis methods. While the efficacy of endoscopic tissue adhesives (ETA) in variceal bleeding has been established, its role in gastrointestinal tumor bleeding (GITB) remains ambiguous., Aims: This study aims to assess the feasibility and effectiveness of ETA in the treatment of GITB., Methods: The study enrolled 30 patients with GITB who underwent hemostasis through Histoacryl® tissue glue injection. Hemostasis success rates, ETA-related adverse events, and re-bleeding rates were evaluated., Results: ETA application achieved successful hemostasis at all tumor bleeding sites, with immediate hemostasis observed in all 30 (100.0%) patients. Among the initially hemostasis cases, 5 patients (17.0%) experienced re-bleeding within 30 days, and the 60 day re-bleeding rate was 20.0% (6/30). Expect for one case of vascular embolism, no adverse events related with ETA application were reported. The 6 month survival was 93%., Conclusion: ETA demonstrated excellent immediate hemostasis success rate in GITB cases and showed promising outcomes in prevention re-bleeding., (© 2024. The Author(s).)

Rationale: Pulmonary tumor thrombotic microangiopathy (PTTM) is a rare but serious complication in patients with malignancy; its main manifestation includes acute pulmonary hypertension with severe respiratory distress. More than 200 cases have been reported since it was first identified in 1990. PTTM accounts for approximately 0.9% to 3.3% of deaths due to malignancy, but only a minority of patients are diagnosed ante-mortem, with most patients having a definitive diagnosis after autopsy., Patient Concerns: Two middle-aged women both died within a short period of time due to progressive dyspnea and severe pulmonary hypertension., Diagnoses: One patient was definitively confirmed as a gastrointestinal malignant tumor by liver puncture biopsy pathology. Ultimately, the clinical diagnosis was pulmonary tumor thrombotic microangiopathy., Interventions: The patient was treated symptomatically with oxygen, diuresis, and anticoagulation, while a liver puncture was perfected to clarify the cause., Outcomes: Two cases of middle-aged female patients with rapidly progressive pulmonary hypertension and respiratory failure resulted in death with malignant neoplasm., Lessons: PTTM has a rapid onset and a high morbidity and mortality rate. Our clinicians need to be more aware of the need for timely diagnosis through a targeted clinical approach, leading to more targeted treatment and a better prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Postoperative delirium (POD) is a common complication among elderly patients after surgery. The Naples Prognostic Score (NPS), a novel prognostic marker based on immune-inflammatory and nutritional status, was widely used in the assessment of the prognosis of surgical patients. However, no study has evaluated the relationship between NPS and POD. The aim of this article was to investigate the association between NPS and POD and test the predictive efficacy of preoperative NPS for POD in elderly patients with gastrointestinal tumors., Materials and Methods: In the present study, we retrospectively collected perioperative data of 176 patients (≥ 60 years) who underwent elective gastrointestinal tumor surgery from June 2022 to September 2023. POD was defined according to the chart-based method and the NPS was calculated for each patient. We compared all the demographics and laboratory data between POD and non-POD groups. Univariate and multivariate logistic regression analysis was used to explore risk factors of POD. Moreover, the accuracy of NPS in predicting POD was further assessed by utilizing receiver operating characteristic (ROC) curves., Results: 20 had POD (11.4%) in a total of 176 patients, with a median age of 71 (65-76). The outcomes by univariate analysis pointed out that age, ASA status ≥ 3, creatinine, white blood cell count, fasting blood glucose (FBG), and NPS were associated with the risk of POD. Multivariate logistic regression analysis further showed that age, ASA grade ≥ 3, FBG and NPS were independent risk factors of POD. Additionally, the ROC curves revealed that NPS allowed better prognostic capacity for POD than other variables with the largest area under the curve (AUC) of 0.798, sensitivity of 0.800 and specificity of 0.667, respectively., Conclusion: Age, ASA grade ≥ 3, and FBG were independent risk factors for POD in the elderly underwent gastrointestinal tumor surgery. Notably, the preoperative NPS was a more effective tool in predicting the incidence of POD, but prospective trials were still needed to further validate our conclusion., Trial Registration: The registration information for the experiment was shown below. (date: 3rd January 2024; number: ChiCTR2400079459)., (© 2024. The Author(s).)

One-third of cancer pain patients do not experience adequate pain relief using analgesic ladder by the World Health Organization. Interventional procedures, such as epidural morphine, have been considered. This study aimed to review the literature comparing the effects of epidural administration of morphine with the oral route. This systematic review included randomized controlled trials (RCTs) conducted with patients with gastrointestinal neoplasm. A search was conducted on PubMed, EMBASE, Web of Science, Scopus, Cochrane Library, and CINAHL databases to identify studies published up to May 2023. The retrieved study was evaluated using the Risk of Bias 2 (RoB 2) tool and qualitatively synthesized. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach (Prospero: CRD42021264728). Only one RCT, a crossover trial, was included in this systematic review. The study was conducted with ten participants (one withdrawal) and reported a statistically significant difference between both subcutaneous and epidural morphine solutions and oral morphine. The adverse events were not described. The included study presents some concerns of bias and low certainty of evidence on the effectiveness and security of epidural morphine administration. The available literature does not suffice to elucidate whether morphine administration via the epidural route is more effective than other routes. Further RCTs are necessary to improve the level of evidence on the effectiveness and risk-benefit of epidural morphine in the management of cancer pain in gastrointestinal neoplasm patients., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cachexia is prevalent in gastrointestinal cancers and worsens patient outcomes and chemotherapy compliance. We examined to what extent registered gastrointestinal cancer chemotherapy clinical trials record measures and related symptoms of cachexia as outcomes, and whether these were associated with trial characteristics., Methods: Four public trial registries (2012-2022) were accessed for Phase II and/or III randomized controlled pancreatic, gastric, and colorectal cancer chemotherapy trial protocols. Trial outcome measures of overall survival and toxicity/side effects, and those related to cachexia [physical activity, weight/body mass index (BMI), dietary limitations, caloric intake, lean muscle mass] and symptoms (appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, and oral mucositis) were extracted, along with the number and types of performance status and patient-reported outcomes (PROs) tools. Data were summarized descriptively. Chi-square tests examined associations between outcomes and trial characteristics (cancer type, trial location, funding source, PROs tools, and commencement year). Statistical significance was set at P < 0.05., Results: We included 540 trial protocols (pancreatic (35.2%), colorectal (33.3%) and gastric (31.5%)), with most trials from Europe (44.1%). Trial lead investigator was from academia (28.3%), industry (27.6%) and government (26.3%). Allied health professional involvement (26.9%) occurred at eligibility. Adjuvant therapy in trials was mainly treatment-related (68.1%). Additional medication included anti-nausea (2.2%) and analgesia (0.9%). Trial protocols mostly recorded overall survival (90.4%) and toxicity (78.9%), and the symptoms appetite loss (26.1%) and diarrhoea (19.1%), with the other symptoms recorded in <10% of the trials. Reporting of physical activity (P = 0.001), dietary limitations (P = 0.002), lean muscle mass (P = 0.027), appetite loss (P < 0.001), pain (P = 0.001), nausea (P = 0.012), and oral mucositis (P = 0.049) varied depending cancer type. Toxicity/side effects (P = 0.022), physical activity (P < 0.001), appetite loss, nausea, and vomiting (all P < 0.001), diarrhoea (P = 0.010), pain (P = 0.001), fatigue/insomnia (P = 0.001) varied depending on the trial location. Trial funding was predominantly from private/industry (34.3%) and influenced the reporting of overall survival (P = 0.049), weight/BMI (P = 0.005), caloric intake (P = 0.015), and pain (P = 0.031). Performance status and PROs tools were mentioned in 91.2% and 46.3% of the trials, respectively. Trials that incorporated PROs tools were more likely to report cachexia related outcomes, except for overall survival, lean muscle mass, and oral mucositis. The proportion of trials measuring weight/BMI increased with trial commencement year (P = 0.04)., Conclusions: Cachexia-related outcomes were under-recorded in gastrointestinal cancer chemotherapy trials. As trial patients experience a high symptom burden, cachexia-relevant measures and symptoms should be assessed throughout the trial, and integrated with primary endpoints to support their progress., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Venous thromboembolism (VTE) chemoprophylaxis is the standard of care after gastrointestinal (GI) cancer surgery; however, variation in risk based on pathologic factors (eg, stage and histology) is unclear. This study aimed to evaluate the association of pathologic factors with VTE after GI cancer surgery., Methods: The American College of Surgeons National Surgical Quality Improvement Program procedure targeted datasets were queried for patients who underwent colorectal, pancreatic, primary hepatic, and esophageal cancer surgery between 2017 and 2020. Disease-specific and pathologic factors associated with postoperative VTE were evaluated using multivariable logistic regression., Results: Among 70,934 patients who underwent GI cancer surgery, the incidence rates of 30-day postoperative VTE were 3.3% for pancreatic cancer, 3.2% for esophageal cancer, 2.7% for primary hepatic, and 1.3% for colorectal cancer. T stage was associated with VTE for colorectal cancer (T4 vs T1; odds ratio [OR], 1.79; 95% CI, 1.24-2.60), pancreatic cancer (all T stages vs T1; P < .05), and primary hepatic cancer (T4 vs T1; OR, 2.80; 95% CI, 1.55-5.08). N stage was associated with VTE for colorectal cancer (N2 vs N0; OR, 1.33; 95% CI, 1.04-1.68) and pancreatic cancer (N2 vs N0; OR, 1.36; 95% CI, 1.03-1.81). M stage was associated with VTE for colorectal cancer (OR, 1.47; 95% CI, 1.17-1.85) and esophageal cancer (OR, 2.54; 95% CI, 1.24-5.19). Histologic subtype was not associated with VTE, except for pancreatic neuroendocrine tumors vs adenocarcinoma (OR, 1.34; 95% CI, 1.03-1.74)., Conclusion: Pathologic factors were associated with higher 30-day VTE risk after GI cancer surgery. Acknowledging the association of pathologic factors on VTE is an important first step to considering a more tailored approach to chemoprophylaxis., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Background: Iron deficiency anemia (IDA) is a prevalent hematological complication associated with gastrointestinal (GI) cancers due to an increased loss of iron and decreased iron absorption. The purpose of this systematic review is to evaluate the use of parenteral iron to treat IDA in patients with GI cancer., Methods: PubMed, Cochrane, EMBASE, CINHAL and Scopus were searched from January 1, 2010 to September 29, 2023 with no language restrictions. We excluded editorials, case reports, abstracts, conference papers, and poster presentations. Studies were included if they discussed IDA, GI neoplasms, use of iron supplementation (with or without erythropoietin-stimulating agents [ESAs]), defined anemia and had an adult patient population. We assessed the efficacy of parenteral iron in comparison to other iron supplementation methods when treating IDA in patients with GI cancer. The Cochrane Risk of Bias Tool 2 (RoB 2) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) assessment tools were used to assess the quality of the included studies. Moreover, the Cochrane Effective Practice and Organization data collection form was used to collect pertinent study information., Results: Our search yielded 3,969 studies across all databases. Twenty-one studies were included (6 randomized control trials; 15 non-randomized studies). Of the 15 studies evaluating hemoglobin (Hb) response, seven studies found an increase in Hb levels when patients were treated with IV iron. The 14 studies evaluating red blood cell (RBC) transfusion rates found conflicting differences in RBC transfusion needs when treated with IV iron. Studies analyzing health related outcomes typically found an increase in quality of life and decreased post-operative complications., Discussion: This review demonstrates improved outcomes of IDA in patients with GI cancer treated with IV iron instead of other iron supplementation methods. Timely diagnosis and appropriate IDA management can greatly improve quality of life in this patient population, especially if myelosuppressive chemotherapy is required., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Christine Brezden-Masley has received research funding from Novartis Pharmaceuticals Canada Inc., Eli Lilly Canada Inc., and Pfizer Canada Inc.; a travel grant from Knight, and honoraria; and has been involved as a consultant for Agendia Inc., Astellas, AstraZeneca, Bristol–Myers Squibb, Eisai, Eli Lilly Canada Inc., Gilead, Knight, Merck Sharp and Dohme LLC, Mylan, Novartis Pharmaceuticals Canada Inc., Pfizer Canada Inc., Roche, Sanofi, Seagen, and Taiho Pharma Canada Inc.., (Copyright: © 2024 Nandakumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Patients undergoing major surgery for gastrointestinal cancer are at high risk of developing or worsening malnutrition and sarcopenia. In malnourished patients, preoperative nutritional support may not be sufficient and so postoperative support is advised. This narrative review addresses several aspects of postoperative nutritional care in the setting of enhanced recovery programmes. Early oral feeding, therapeutic diet, oral nutritional supplements, immunonutrition, and probiotics are discussed. When postoperative intake is insufficient, nutritional support favouring the enteral route is recommended. Whether this approach should use a nasojejunal tube or jejunostomy is still a matter of debate. In the setting of enhanced recovery programmes with early discharge, nutritional follow-up and care should be continued beyond the short time in hospital. In enhanced recovery programmes, the main specific aspects of nutrition are patient education, early oral intake, and post-discharge care. The other aspects do not differ from conventional care., Competing Interests: Declaration of competing interest P Funk Debleds and C Chambrier declare no competing interests related to this review. K Slim declares competing interests with Viatris and Merck, but with no relationship with this review., (Copyright © 2023 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Objectives: This study was conducted to determine the effects of illness perception on death anxiety and satisfaction with life in patients with advanced gastrointestinal cancer., Methods: This cross-sectional and correlational study was conducted with 125 patients with cancer who were admitted to the oncology clinic of a university hospital in the Central Anatolian Region of Turkey between March and December 2022 and who met the research criteria and accepted to participate in the study. The data were collected with "Patient descriptive information form," "Brief Illness Perception Questionnaire (BIPQ)," "Scale of Death Anxiety (SDA)," and "Satisfaction with Life Scale (SWLS).", Results: It was found that mean BIPQ score of the patients was 39.54 ± 12.82, the mean SDA score was 8.02 ± 3.16, and the mean SWLS score was 14.74 ± 5.19. BIPQ total score was found to affect SDA total score positively ( β  = .751) and SWLS total score negatively ( β  = - .591). SDA total score was found to affect SWLS total score negatively ( β  = -.216) ( p  < .05)., Significance of Results: It was found that patients with advanced gastrointestinal cancer had moderate level of illness perception and life satisfaction, and high death anxiety. It was found that as illness perception of the patients increased, their death anxiety increased and satisfaction with life decreased. In addition, it was found that as the death anxiety of patients increased, their satisfaction with life decreased.

Objective: Various psychological interventions have been demonstrated to be effective at preventing anxiety and depression symptoms in patients with gastrointestinal (GI) cancer. However, it remains unclear which intervention is the best option. This study aimed to evaluate the impact of various psychological interventions on anxiety and depression in symptomatic patients with GI cancer., Methods: The PubMed, Cochrane Library, Embase, CNKI, WanFang Data, and VIP databases were systematically searched from inception to June 2023 to identify randomized controlled trials (RCTs). The primary outcomes were anxiety and depression levels. Two reviewers independently selected the studies, extracted the data based on prespecified criteria, and evaluated the risk of bias using the Cochrane Collaboration risk of bias tool. Stata 14.0 was used to conduct network meta-analysis., Results: Thirty-two RCTs (2453 patients) involving 9 psychological interventions were included. The results of the network meta-analysis showed that cognitive-behavioral therapy (CBT; mean difference [MD] = -4.98, 95% CI (-7.04, -2.93), relaxation therapy (MD = -4.39, 95% CI (-7.90, -0.88), reminiscence therapy (MD = -5.01, 95% CI (-8.20, -1.81)), and narrative nursing (MD = -4.89, 95% CI (-8.54, -1.23)) significantly reduced anxiety levels, and CBT (MD = -2.15, 95% CI (-4.28, -0.02), reminiscence therapy (MD = -7.20, 95% CI (-10.48, -3.91), and narrative nursing (MD = -7.20, 95% CI (-10.48, -3.91)) significantly reduced depression levels in patients with GI cancer compared with conventional nursing care., Conclusion: The findings of this network meta-analysis revealed that CBT, reminiscence therapy and narrative nursing can be actively considered as part of sequential therapy to reduce anxiety and depression levels in patients with GI cancer., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Longitudinal change in patient-reported cognitive complaints (CC) in older adults with cancer is poorly understood. The purpose of this study was to evaluate early longitudinal CC and predictors among older adults with cancer., Methods: We examined early CC change on the PROMIS® Short Form4a Cognitive Function among adults ≥ 60 years with GI cancer enrolled in the Cancer and Aging Resilience Evaluation (CARE) undergoing geriatric assessment (GA) at baseline and one 3-6-month follow-up. Multivariable linear regression examined associations of demographics, socioeconomics, GA domains, baseline cognitive score, and treatment toxicities on follow-up cognitive score. Bayesian analysis of covariance (ANCOVA) determined best fitting model., Results: A total of 218 participants were included. The median follow-up was 3.7 months, the mean age was 69.2 ± 7.1, and 57.3% were male. The most common cancer was colorectal (30.7%) with most stage III/IV (73.7%). About half (51.8%) had stable cognition baseline to follow-up (follow-up t-score ± 5 points of baseline), 20.6% improved (≥ 5 increase), and 27.5% declined (≥ 5 decrease). After adjustment, there were no significant baseline predictors of follow-up cognitive t-score. Baseline t-score was the best-fitting predictor of follow-up t-score., Conclusions: In this first study, examining early change in CC among older adults with cancer, ~ 28% exhibited cognitive decline. Baseline cognition is the most important early predictor of follow-up cognition. Longer follow-up is needed to identify long-term predictors of CC change in cancer survivors., Implications for Cancer Survivors: Cognitive decline, even early, may occur in many older adults with cancer. Baseline and regular follow-up assessments of cognitive symptoms are an important component of survivorship care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Patients with metastatic upper gastrointestinal (GI) cancer may experience a large physical symptom burden. However, less is known about existential, social, and psychological symptoms. To provide the patient with palliative care, quality-of-life questionnaires are used for structured needs assessment. These are sporadically implemented, and there seems to be uncertainty to the efficiency of current practice. The aim of study was to explore the experienced assessment-process and treatment of palliative symptoms, as well as the experienced symptom burden, in patients with metastatic upper GI cancer., Methods: Qualitative, semi-structured interviews were conducted in 10 patients with metastatic upper GI cancer. Data were analyzed using content analysis., Results: The patients did not expect treatment for all physical symptoms. Existential symptoms revolved around death and dying, social issues were mainly related to family, and psychological issues were based in the continuous dealing with serious illness. Existential, social, and psychological symptoms were mostly not considered part of the expected care when admitted to hospital. Patients had only vague recollections of their experiences with structured needs assessment, and the process had been inconsequential in the treatment of symptoms., Significance of Results: Patients with upper GI cancer experience symptoms related to all 4 areas of palliative care being physical, existential, social, and psychological, but these are differentiated in the way patients perceive their origins and treatability. Structured needs assessment was not routinely carried out, and in cases where this had been done, no follow-up was effectuated. This calls for increased focus and proper implementation for the process to be relevant in the treatment of palliative symptoms.

Background: Gram-negative rod (GNR) bacteremia has been suggested as a clinical marker of occult cancer; however, no studies are available in this regard in the Japanese population. Here, we investigated the risk factors for gastrointestinal cancer with GNR bacteremia., Methods: Patients with GNR bacteremia admitted to St. Luke's International Hospital between January 2011 and July 2021 were included. The clinical data of patients with and without cancer, 1 year before and after GNR bacteremia diagnosis, were compared. Univariate analysis was performed using χ2 and Fisher's exact tests for categorical variables and the Mann-Whitney U test for continuous variables, while multivariable analysis was performed using logistic regression analysis, and a P of <0.05 was considered statistically significant., Results: Of 2,296 GNR bacteremia-positive patients, 96 were associated with gastrointestinal cancer, and univariate analysis showed significant differences between the gastrointestinal cancer and comparison groups in terms of mean body mass index (BMI; 20.5 vs. 21.8 kg/m2), Enterobacterales detection (64.6% vs. 81.3%), and anaerobic GNR detection (24.0% vs. 8.5%). Thirty-five (36%) and 61 (64%) patients had upper and lower gastrointestinal cancer, respectively. There were 23 patients with anaerobic GNR bacteremia related to 24 strains (upper and lower gastrointestinal cancer, 5 and 18 cases, respectively). Multivariate analysis identified anaerobic GNR [odds ratio, 3.440; 95% confidence interval (CI): 2.085-5.675, P<0.001] as a significant risk factor for cancer., Conclusions: Anaerobic GNR in blood cultures may be a risk factor for gastrointestinal cancer. Therefore, it is necessary consider cancer workup, such as endoscopy, for patients with anaerobic GNR bacteremia.

Background: Gastritis cystica profunda (GCP), commonly observed in remnant gastric anastomosis, is associated with developing gastric cancer., Case: This case report describes a patient with GCP in a previously unoperated stomach that mimicked a pyloric submucosal tumor and caused anorexia, which is rare in clinical practice., Patient Concerns: A 72-year-old woman presented with loss of appetite and weight., Diagnoses: Gastroscopy detected a 20 mm diameter submucosal tumor near the pylorus. Computed tomography and magnetic resonance imaging identified a cystic lesion, unlike a usual submucosal tumor in the stomach. The diagnosis was difficult, even with endoscopic ultrasound-guided fine-needle aspiration., Interventions: Surgery was performed for diagnosis and treatment. The lesion was resected using a submucosal dissection technique after an incision of the gastric wall during open laparotomy. Histopathological examination confirmed the diagnosis of GCP and revealed no dysplasia or cancer., Outcomes: Anorexia resolved after the surgery. Residual or recurrent lesions were not detected during follow-up examinations performed 1 year after surgery., Lessons: GCP occurring in a previously unoperated stomach as a macroscopic lesion like a submucosal tumor causing some symptoms is rare. GCP is associated with a risk of developing cancer. Therefore, careful evaluation and management during treatment are required., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background & Aims: Progresses in management make a higher proportion of cirrhotic patients with gastrointestinal (GI) cancer candidates to chemotherapy. Data are needed on the safety and liver-related events associated with the use of chemotherapy in these patients., Methods: Forty-nine patients with cirrhosis receiving chemotherapy against GI cancer from 2013 to 2018 were identified in the French Health Insurance Database using ICD-10 codes K70-K74, and matched 1:2 to non-cirrhotic controls (n = 98) on age, tumour type and type of treatment. Adverse events (AE), dose tapering, discontinuation rate, liver-related events and survival rate were compared., Results: Patients with cirrhosis (Child-Pugh A 91%) more often received lower doses (38.8% vs 7.1%, p < .001), without significant differences in terms of grade 3/4 AE or dose tapering rates (29.6% vs. 36.7%; 22.3% vs 24.4%, respectively). Treatment discontinuation rate was higher in patients with cirrhosis (23.3% vs. 11.3%, p = .005). Child-Pugh (p = .007) and MELD (p = .025) scores increased under chemotherapy. Five patients with cirrhosis (10.2%) had liver decompensation within 12 months, and 17.2% of deaths in the cirrhosis group were liver-related versus 0% in matched controls. WHO-PS stage > 1 (HR 3.74, CI95%: 2.13-6.57, p < .001), TNM-stage M1 (HR 3.61, CI 95%: 1.82-7.16, p < .001), non-colorectal cancer (HR 1.73, CI 95%: 1.05-2.86, p = .032) and bilirubin higher than 5 mg/dL (HR 2.26, CI 95%: 1.39-3.70, p < .001) were independent prognostic factors of 2-year mortality, whereas cirrhosis was not., Conclusions: Chemotherapy should be proposed only in patients with compensated cirrhosis with close monitoring of liver function. Dose management remains challenging. Multidisciplinary management is warranted to improve these patients' outcomes., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Objectives: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available., Methods: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982., Results: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second-line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow-up time (P = 0.19) or in the recurrence rate (P = 0.45)., Conclusion: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second-line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: The incidence of early-onset obesity-related cancers (diagnosed < 50 years) is increasing in the U.S. We examined the reported historical body mass index (BMI) of adults with early and later-onset cancers to explore relation to obesity., Methods: We queried the 1999-2018 NHANES database for adults diagnosed with obesity-related cancers (colorectal, non-colorectal gastrointestinal, uterine, breast). We classified early and late-onset cancer based on a diagnosis age of < 50 and ≥ 50 years, respectively. Propensity-weighted analysis was used to compare prior historical BMIs between the matched groups., Results: After weighing, we included 2,966,528 patients with obesity-related cancers, 846,211 (28%) of which were < 50 years. In the matched analysis, 69.1% of early-onset CRC cases were diagnosed as obese (BMI ≥ 30 kg/m 2 ) before cancer diagnosis, compared to 47.2% of late-onset cases (p < 0.03). Similarly, a higher percentage of adults with other early-onset gastrointestinal cancers had prior obesity as compared to the late-onset cohort (70.3% vs. 40.5%, p = 0.0002). BMI showed a trend toward higher values at ages 20-24 for early-onset CRC and 30-34 for other gastrointestinal cancers. In contrast, later-onset CRC and other gastrointestinal cancers exhibited higher BMI values at later ages (30-34 and 35-39, respectively). Early-onset uterine cancer was linked to a higher BMI compared to later-onset cancer (34.0 vs. 31.1 kg/m 2 , p < 0.0001), with a trend towards a higher BMI before 19 years old., Conclusions: Our nationally representative data reveal that higher and earlier body fatness in adulthood associates with early-onset gastrointestinal and uterine cancers. These findings underscore the importance of intensifying efforts to combat early-life obesity., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)