Malnutrition in patients with gastrointestinal (GI) cancers can be the result of functional and/or anatomical changes in the alimentary tract, secondary to malignancy or oncologic therapies. Understanding the underlying mechanisms of malnutrition in these patients is imperative in providing appropriate interventions that can not only improve quality of life for these individuals, but also improve their tolerance of oncologic treatment and progression towards remission or cure. In this narrative review, we address common nutritional deficiencies associated with GI malignancies, including pancreatic, biliary, and hepatic cancers. Furthermore, we address common issues related to these deficiencies and causes of nutrition barriers as they relate to organ malfunction or surgical alterations of anatomy. Recommendations for counseling, dietary modifications, nutritional supplements, and pharmacologic interventions are provided based on individual barriers and the vital role of multidisciplinary care is highlighted. Additionally, we highlight novel techniques, such as the role of psychosocial care, prehabilitation, digital health, and machine learning, which can improve nutritional outcomes, provide patient-directed care, and improve risk stratification for this complex and multifaceted issue that faces patients diagnosed with GI cancers.

Background: Sleep disturbance (SD) is very common in breast cancer (BC) patients, resulting in poor therapeutic efficacy and prognosis. Diet may be associated with SD through systemic inflammation. This study aimed to evaluate the association between the energy-adjusted Dietary Inflammatory Index (E-DII) and SD, as well as the potential mediating role of inflammatory biomarkers in patients with BC. Methods: In this cross-sectional study, 302 BC patients were recruited, from whom 103 blood samples were obtained for the determination of plasma inflammatory biomarkers. Dietary intake was evaluated using 3-day, 24 h dietary recalls, while SD was assessed using the Pittsburgh Sleep Quality Index (PSQI). Results: SD was observed in 91 (30.13%) patients, who exhibited significantly higher E-DII scores, C-reactive protein (CRP), interleukins (IL-1β, IL-6, and IL-10), and tumor necrosis factor-α (TNF-α) levels compared to non-SD participants (p < 0.05). After adjusting for covariates, for every 1-point elevation in E-DII, the risk of SD increased by 23.0% (OR = 1.23; 95% CI: 1.04, 1.44; p = 0.014). Among the E-DII components, only vitamin C showed an inverse correlation with SD (OR = 0.99; 95% CI: 0.99, 1.00; p = 0.015). Mediation analysis showed that IL-1β, IL-10, IL-6, TNF-α, and CRP statistically mediated the association between E-DII and SD (all p < 0.05). The sensitivity parameters ρ were 0.3, 0.5, 0.4, 0.4, and 0.4, respectively. Conclusions: A diet with pro-inflammatory potential was correlated with SD among BC patients, which might be mediated by circulating IL-1β, IL-10, IL-6, TNF-α, and CRP.

Background/Objectives: Iodine intake influences thyroid-related and metabolic diseases that have important public health implications. However, longitudinal evidence of the association between iodine intake and mortality remains scarce and limited to Western populations. Given the markedly high iodine intake among Asians and possible ethnic or regional differences in iodine sensitivity, population-based data from Asian cohorts are needed. Methods: We analyzed 5497 adults from the Korean National Health and Nutrition Examination Survey (2013-2015) linked with mortality follow-up through 2021. Urinary iodine concentration (UIC) was quantified from spot urine samples using inductively coupled plasma mass spectrometry. Iodine intake was estimated from UIC and categorized into four groups: below the estimated average requirement, low-normal, high-normal, and above the tolerable upper level (UL). The primary outcome was all-cause mortality. Cardiovascular disease-specific and cancer-specific mortality were also assessed. Multivariable Cox proportional hazards models accounting for the complex survey design were used to estimate hazard ratios and 95% confidence intervals. Sensitivity analysis excluded participants with thyroid disease or early death, and subgroup analyses by age and sex were also conducted. Results: During a median 8.4-year follow-up, 139 deaths occurred. Compared with the low-normal intake group, excessive iodine intake (above UL) was not associated with all-cause mortality (HR 1.09, 95% CI 0.36-3.27), cardiovascular mortality (HR 1.27, 95% CI 0.21-7.61), or cancer mortality (HR 1.71, 95% CI 0.40-7.29). No significant trends were observed across intake categories (p > 0.2), and similar findings were obtained when UIC levels were analyzed. Excluding participants with thyroid disease or early death did not change the results, and no significant interaction was observed by age or sex. Conclusions: In this first population-based Asian study on iodine intake to mortality, neither estimated iodine intake nor UIC was associated with all-cause mortality. These results suggest that the relationship between iodine exposure and mortality may differ across populations, underscoring the need for further large-scale studies.

We conducted the first epidemiologic study to examine the dose-response relationship between body mass index (BMI) and the likelihood of reporting an overall cancer diagnosis, along with the association between overweight or obese and cancer diagnosis among college students in the United States.

The American College Health Association-National College Health Assessment (ACHA-NCHA) self-reported, cross-sectional data on demographic information, physical activity, BMI, smoking status, and overall cancer from 2019 to 2022 (n = 275,185; 0.08% cancer cases) were used. A cubic spline model and logistic regression analyses were performed to evaluate associations between BMI and the likelihood of reporting a cancer diagnosis, adjusting for relevant covariates.

The cubic spline observed that higher BMI (kg/m²) was associated with a greater likelihood of reporting an overall cancer diagnosis after adjusting for age, sex, race, ethnicity, education level, physical activity, and smoking status (p for linear relation = 0.02 and p for overall association < 0.0001). Specifically, each 1 kg/m² increase in BMI was associated with a 1% increase in the odds of a cancer diagnosis. Multivariable-adjusted logistic regression analyses revealed that both overweight (30 > BMI ≥ 25 kg/m²) [odds ratio (OR): 1.20 (95% confidence interval (CI): 1.08-1.34)], and obesity (BMI ≥ 30 kg/m²) [1.48 (1.32-1.65)] were positively associated with a cancer diagnosis.

Higher BMI, especially overweight/obesity, was associated with a greater likelihood of reporting a cancer diagnosis among college students in the United States. To prevent and control cancer, targeted interventions aimed at maintaining a healthy weight in this population are warranted.

Owing to concerns about overdiagnosis and overtreatment associated with prostate-specific antigen (PSA) screening for early prostate cancer detection, recent guidelines have lowered the PSA cutoff value for recommending biopsy. This study aimed to evaluate the diagnostic accuracy of a lower PSA cutoff value in Korean men and to explore whether additional clinically useful criteria can be proposed.

A retrospective cohort study of 17,539 Korean men who underwent their first prostate biopsy due to lower urinary tract symptoms was conducted at six tertiary hospitals between 2011 and 2019. The diagnostic performance of various PSA and PSA density (PSAD) cutoff values across age groups was evaluated by analyzing the data on demographics, PSA levels, PSAD, and biopsy results.

Among the participants, 44.1% were diagnosed with prostate cancer, of whom 73.7% had clinically significant cancer (Gleason score ≥7). No significant differences in cancer detection rates were found between PSA levels of 3-4 ng/mL and 4-5 ng/mL across age groups. PSAD further increased the area under the receiver operating characteristic curve by 5.5%-11.4%.

These findings suggest that diagnostic yield may not be impacted by merely lowering the PSA cutoff. Rather, combining PSA, PSAD, and patient age enhances screening accuracy while minimizing unnecessary biopsies and overdiagnosis. Our results highlight the need for more data to refine national screening guidelines and promote a more tailored approach to prostate cancer screening in Korea.

Radical cystectomy (RC), which is the standard of care for muscle-invasive and high-grade noninvasive bladder cancer, is accompanied by postoperative renal function deterioration. We aimed to evaluate the effect of serum albumin level on postoperative renal function decline after RC.

A total of 272 patients with estimated glomerular filtration rate (eGFR) ≥60 mL/minute/1.73 m² who underwent RC between October 2003 and December 2020 were included. Acute kidney injury (AKI) was defined according to the KDIGO (Kidney Disease Improving Global Outcomes) criteria, while postoperative chronic kidney disease (CKD) progression was defined as an eGFR <60 mL/minute/1.73 m² at ≥3 months after RC.

In our cohort, 20 (7.4%) and 99 (36.4%) patients experienced postoperative AKI and CKD progression, respectively, with a median follow-up period of 51.5 months. The median preoperative serum albumin level and eGFR were 4.1 g/dL and 82.0 mL/minute/1.73 m², respectively. Preoperative serum albumin less than the median (4.1 g/dL) was associated with postoperative AKI (odds ratio [OR] 3.76, p=0.027) and CKD progression (OR 2.87, p<0.001) after adjusting for other factors.

Serum albumin level <4.1 g/dL was associated with short- and long-term renal function decline after RC, suggesting that close monitoring of renal function after RC might be considered in these patients.

To develop and validate an artificial intelligence (AI)-based personalized outcome prediction model for upper-urinary tract urothelial carcinoma patients undergoing radical nephroureterectomy.

Data from patients who underwent radical nephroureterectomy between 2010 and 2020 across three hospitals were retrospectively analyzed. A model was developed using one tertiary center's data and externally validated with data from two other hospitals. An AI model using XGBoost as risk estimator and bootstrapped Weibull Accelerated Failure Time model for 10-year survival probability was employed. Hyperparameter tuning used Optuna method. Model efficacy was assessed using concordance index, average Brier score, D-calibration, and six-month interval time-dependent area under the curve (AUC).

Of 1,039 patients, 627 qualified after excluding 50 with neoadjuvant chemotherapy. Model development used 564 patients (507 training, 57 test) with 9:1 stratified random split, plus 63 for internal validation and 362 for external validation. Significant parameters included preoperative glomerular filtration rate (p<0.001), hydroureteronephrosis (p=0.013), pathological N stage (p<0.001), concurrent carcinoma in situ (p<0.001), disease progression (p<0.001), and survival rate (p<0.001). Disease-free survival (DFS) model's concordance index: internal validation 0.789, external validations 0.734 and 0.771. Overall survival (OS) model's concordance index: internal validation 0.819, external validations 0.780 and 0.771. Mean time-dependent AUC was 0.66-0.77 for DFS and 0.67-0.80 for OS during 10-year periods.

AI-based model effectively predicts disease-free and OS outcomes for upper-urinary tract urothelial carcinoma patients with post-radical nephroureterectomy, showcasing robust performance across multicenter settings.

Immunotherapy is considered a promising treatment approach for advanced biliary tract cancers (BTCs), but only a small number of patients can respond to immunotherapy. This study aimed to develop and validate a clinical-radiomics nomogram integrating radiomic features from lymph nodes (LNs) for predicting immunotherapy efficacy in advanced BTCs.

A total of 258 patients with advanced BTCs were enrolled, comprising 206 patients in the retrospective cohort and 52 patients in the prospective cohort. Radiomic features were extracted from the LNs. The maximum relevance and minimum redundancy and least absolute shrinkage and selection operator were used to develop the radiomics signature (Rad-score). Univariate analysis and multivariate logistic regression (LR) were used to construct the clinical model. A clinical-radiomics nomogram was constructed using LR. The performance of all the models was analyzed using receiver operating characteristic curves.

Nine radiomic features were combined to construct the Rad-score. The nomogram incorporated the six clinical parameters and the Rad-score, and achieved the best discriminative ability with the areas under the curve (AUCs) of 0.899, 0.843 and 0.874 in the training, validation and testing cohorts. The clinical model showed better predictive performance than the Rad-score with the AUCs of 0.834, 0.878 and 0.740 in the training, validation and testing cohorts. The calibration curve and Brier score indicated the goodness-of-fit of the nomogram. Patients with higher nomogram scores had better overall survival (OS) and progression-free survival (PFS) in comparison to those with low scores.

The clinical-radiomics nomogram showed promising performance for predicting the response to immunotherapy in patients with advanced BTCs.

Mitochondrial antiviral signaling protein (MAVS), a central adaptor in cytosolic RNA sensing, is critical for antitumor innate immunity and maintains mitochondrial homeostasis via its mitochondrial localization. Mitochondrial dysfunction acts as a key driver and amplifier of the senescence-associated secretory phenotype (SASP), a double-edged sword in tumor progression. However, whether tumor-intrinsic MAVS can regulate antitumor immunity via cellular senescence independently of its well-established interferon signaling remains unclear.

Our study employed an integrated strategy. Clinically, we profiled MAVS expression and its association with prognosis and immune infiltration in renal tumor specimens. Mechanistic insights into tumor-intrinsic MAVS were gained through a battery of techniques spanning quantitative PCR, immunoblotting, RNA sequencing, senescence and mitochondrial function assays, confocal imaging, immunohistochemical, mass spectrometry, and co-immunoprecipitation. In vivo, we used MAVS-deficient models combined with CD8⁺ T-cell depletion, programmed cell death protein-1 (PD-1) blockade, or reactive oxygen species (ROS) scavenging by N-acetylcysteine (NAC), with immune infiltration characterized by flow cytometry.

Clinical evidence links elevated MAVS expression in renal tumors to poor prognosis and diminished CD8⁺ T-cell infiltration. Strikingly, tumor-intrinsic MAVS deficiency curbed malignant progression by triggering cellular senescence and fostering a permissive niche for CD8⁺ T-cell activation and recruitment. Mechanistically, MAVS orchestrates mitochondrial integrity by co-localizing with and stabilizing chemokine-like factor-like MARVEL transmembrane domain-containing 6 (CMTM6), thereby shielding it from lysosomal degradation. Disruption of this axis provoked mitochondrial dysfunction and ROS accumulation, culminating in senescence and an SASP marked by chemokine C-C motif ligand 3 (CCL3). Thus, despite dampening canonical innate immune signaling, MAVS deletion unleashed potent antitumor immunity via CCL3-mediated CD8⁺ T-cell recruitment, an effect abolished by CD8⁺ T-cell depletion or ROS scavenging with NAC. Leveraging this paradigm, we demonstrated that tumor-specific MAVS deficiency acts synergistically with PD-1 blockade to achieve robust therapeutic efficacy.

Our findings establish the tumor-intrinsic MAVS/CMTM6/CCL3 axis as a previously unrecognized critical regulator of senescence-driven antitumor immunity in renal carcinoma. Therapeutic targeting of this axis presents a promising strategy to curtail tumor progression and potentiate immunotherapy.

Bladder cancer ranks as the 11th most frequent form of cancer and is the most common malignancy of urinary tract cells. A major contributor to bladder cancer development is oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and is found to regulate oxidative stress in cancer cells. This study aimed to investigate the relationship between oxidative stress and the NRF2/TAZ pathway in bladder cancer. In this study, a total of 35 bladder cancer patients and 35 healthy subjects were recruited. The expression of NRF2 and TAZ genes was evaluated using real-time PCR. Total Oxidant Status (TOS) and total antioxidant capacity (TAC) of the samples were measured. Our findings revealed a higher expression of NRF2 (p < 0.001) and TAZ (p < 0.001) mRNA in cancerous tissue as compared to healthy subjects. We also found that there is a positive correlation between tumor grading and NRF2 (r = 0.522, p = 0.001) as well as TAZ (r = 0.462, p = 0.02) genes mRNA expression. Also, our results revealed that there is a significant correlation between TAZ and NRF2 genes mRNA expression in bladder cancer patients. Furthermore TAC level was considerably lower in bladder cancer patients (p < 0.01), while the TOS level was significantly higher compared to the control group(p < 0.05). Finally, our findings suggested that NRF2 and TAZ, as transcriptional factors, are associated with higher grades of bladder cancer as well as oxidative stress in patients with bladder cancer.