With advances in surgical treatment for gastric cancer and improvements in long-term prognosis, increasing attention has been directed toward late nutritional complications. This retrospective study focused on body composition as an indicator of nutritional status, aiming to elucidate mid- to long-term changes following minimally invasive gastrectomy (MIG). A total of 102 3-year cancer survivors who underwent curative laparoscopic or robotic gastrectomy were included. Body composition indices, including subcutaneous fat, visceral fat, and skeletal muscle, were calculated using multidetector computed tomography images. All indices decreased relative to preoperative levels and remained lower during long-term postoperative follow-up. The reduction was more pronounced during the mid-term period. Although the body fat indices demonstrated a slight trend toward recovery, skeletal muscle showed persistently reduced levels in the long term. Multiple regression analysis revealed that only total gastrectomy (MITG) was identified as an independent predictor of reductions in all indices (all P < 0.01). When stratified by the extent of gastrectomy, the postoperative values of all indices were lower in the MITG group than in the distal gastrectomy group. To address late nutritional complications following MIG, particular attention should be paid to the mid-postoperative period, when nutritional status reaches its lowest point, as well as to patients undergoing MITG.
Fasting-mimicking diet (FMD) exerts antitumor effects in multiple cancer types, but the role of neural regulation remains unclear. Here, we investigated the involvement of peripheral and central nervous systems in FMD-mediated suppression of colorectal cancer using a murine MC38 tumor model. Cyclic FMD treatment significantly inhibited tumor growth. Three-dimensional imaging revealed abundant neural fibers within colorectal tumor tissues. To assess the contribution of distinct neural pathways, enteric denervation, vagotomy, sympathetic denervation, and sensory nerve ablation were performed. Enteric denervation markedly attenuated the antitumor effect of FMD, whereas vagal, sympathetic, and sensory denervation had limited impact. In addition, c-Fos immunofluorescence demonstrated region-specific central neural responses to FMD, including increased neuronal activation in the arcuate nucleus and insular cortex and altered activity in the rostral ventrolateral medulla. These findings suggest that neural signaling contributes to the antitumor effects of FMD and implicate enteric nerves in this response. Our study highlights the potential involvement of both peripheral and central neural pathways in the regulation of colorectal cancer progression during dietary intervention.
Purpose: Acute Myeloid Leukemia (AML) is a highly aggressive hematological malignancy driven by mutations in early hematopoietic cells, leading to uncontrolled myeloid cell proliferation. The development of efficacious and less toxic therapies remains a critical challenge.Methods: Herein, we evaluated the anti-leukemic potential of a 70% tocotrienol-enriched fraction (TEF), a vitamin E isoform, using different AML models.Results: TEF demonstrated selective cytotoxicity against AML cells, evidenced by low IC50 values and significant induction of apoptosis in AML cell lines and primary AML patient samples, with minimal impact on nonmalignant cells. Mechanistic studies revealed that the TEF treatment disrupted mitochondrial function, leading to reduced mitochondrial membrane potential and ROS generation in AML cells. This triggered the intrinsic apoptotic pathway, as indicated by decreased BCL2 and increased active caspase-3 levels. In a 3D bone marrow niche co-culture system, the treatment with TEF effectively diminished AML cell populations (OCI-AML3 and primary AML cells) while preserving mesenchymal stromal cells and endothelial cells. Importantly, administration of TEF reduced AML burden in leukemic mice.Conclusions: These comprehensive results suggest that the 70% tocotrienol-enriched fraction holds significant promise as a selective anti-neoplastic agent for AML, capable of targeting leukemic cells even within the protective bone marrow microenvironment.
Women with breast cancer experience body composition and dietary changes, which may lead to reduced muscle strength (MS) and muscle mass. This study aimed to analyze the relationship between MS and dietary protein intake in this population. A cross-sectional study was conducted with women aged over 20 years diagnosed within ≤12 months. Sociodemographic, behavioral, clinical, and anthropometric data were collected. MS was assessed based on handgrip strength. Food intake was estimated using a food frequency questionnaire. Adjusted binary logistic regression was performed (p < 0.05). The sample comprised 149 women (mean age: 55.6 ± 11.2 years). Most participants self-identified as black or brown (67.1%), had invasive lobular carcinoma (66.4%), and were overweight (35.6%), while 28.2% exhibited low grip strength. The group with low MS had higher intakes of carbohydrates, plant protein, and magnesium as well as lower intakes of total fat, total protein, and animal protein (p < 0.05 for all). Each additional gram/day of animal protein was associated with a 7% reduction in the likelihood of having low muscle strength (β = -0.042; OR = 0.93; 95% CI: 0.921-0.977; p = 0.035). Animal protein intake was inversely associated with low muscle strength in women with breast cancer.
Although anamorelin improves appetite and body composition in cancer cachexia, early discontinuation is common. We aimed to evaluate predictors of 12-week treatment completion and longitudinal changes among patients who completed treatment. This single-center, retrospective study included patients with advanced gastrointestinal cancer who received anamorelin for cachexia (July 2021-March 2025). Baseline factors were compared between continuation and discontinuation groups, and predictors were assessed using multivariable logistic regression. Of 89 eligible patients, 36 (40.4%) completed 12 wk of treatment. In multivariable analyses, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥1 (OR, 0.39; 95% CI, 0.15-0.98; p = 0.048) and neutrophil-to-lymphocyte ratio (NLR) ≥3.0 (OR, 0.35; 95% CI, 0.12-0.95; p = 0.047) were associated with lower treatment completion. In another model, NLR ≥3.0 remained significantly associated with lower treatment completion, while concurrent systemic anticancer therapy at anamorelin initiation showed a nonsignificant association with treatment completion (OR, 4.42; 95% CI, 0.92-43.07; p = 0.064). In the continuation group, nutritional status, body composition, handgrip strength, and anorexia-related symptoms improved, whereas NLR increased. Impaired ECOG PS and elevated NLR were associated with failure to complete 12-week anamorelin treatment. Earlier initiation of anamorelin before performance status declines and systemic inflammation progresses may support treatment completion.
Weight loss is a common symptom in patients with esophageal cancer and can negatively impact survival outcomes. This meta-analysis aimed to systematically evaluate the relationship between weight loss and survival outcomes in individuals diagnosed with esophageal cancer. We conducted a comprehensive search of PubMed, Embase, and Web of Science for studies reporting the association between weight loss and overall survival or progression-free survival in patients with esophageal cancer. Pooled adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using a random-effects model. Eleven studies involving 3,566 esophageal cancer patients were included. The pooled results indicated that weight loss was significantly associated with poorer overall survival (HR 1.68; 95% CI 1.49-1.90) and progression-free survival (HR 1.61; 95% CI 1.39-1.86). Subgroup analyses revealed a numerically higher HR for overall survival in patients aged 60 years or younger, those assessed for weight loss during treatment, patients with a follow-up duration exceeding 36 months, and individuals diagnosed with squamous cell carcinoma. Weight loss was significantly associated with poorer overall survival in patients with esophageal cancer. Regarding progression-free survival, a preliminary pooled analysis based on only two studies suggested a potential association; however, this finding requires confirmation in future research.
In gastric cancer (GC) patients, malnutrition is associated with a worse prognosis. Decreases in body mass index (BMI) can reflect malnutrition. Here, we determined whether preoperative time-dependent changes (Δ/day) in BMI provide better prognostic insights than single point-in-time measurements of BMI. A single-center retrospective analysis of 140 GC patients was performed. BMI was measured at both the initial surgical visit and then again at the time of hospitalization for surgery. ΔBMI/day was determined. Associations with time to surgery, intraoperative blood loss, tumor stage, and survival were determined. ΔBMI/day was strongly associated with time to surgery (P = 0.001), magnitude of intraoperative blood loss, tumor stage, progression-free survival (PFS), and overall survival (OS) (all Ps <0.001). In multivariable Cox analyses adjusted for age, sex, Eastern Cooperative Oncology Group Performance Status, pathological stage, surgical approach, blood loss, time-to-surgery, and static BMI measurements, large ΔBMI/day was associated with worse PFS (hazard ratio 2.81, 95% confidence interval 1.07-7.42, P = 0.037) whereas static measurements of BMI at the time of the initial visit or surgery were not independently associated with PFS. ΔBMI/day was not independently associated with OS. In conclusion, preoperative changes in BMI/day provide better prognostic insights, particularly for PFS, compared to measurements of BMI at a single point in time.
Background: Liver regeneration is essential after hepatectomy, but it is frequently impaired in patients with hepatocellular carcinoma (HCC) due to cirrhosis, metabolic dysfunction, sarcopenia, malnutrition, aging, and systemic inflammation. Post-hepatectomy liver failure remains a major clinical challenge. Objective: This review summarizes metabolic mechanisms underlying liver regeneration and explores metabolic vulnerabilities in patients with HCC, along with emerging therapeutic strategies to enhance regenerative capacity. Methods: A narrative review of current literature was conducted focusing on hepatic regenerative biology, metabolic reprogramming, and clinical metabolic interventions relevant to perioperative liver care. Results: Liver regeneration is regulated not only by growth factor signaling but also by coordinated metabolic reprogramming, including energy metabolism, lipid oxidation, amino acid homeostasis, mitochondrial function, and inter-organ crosstalk. Patients with HCC often exhibit impaired regenerative metabolism. Emerging interventions include nutritional optimization, branched-chain amino acid supplementation, L-carnitine administration, exercise-based prehabilitation, and modulation of the gut-liver axis. L-carnitine is highlighted as a mitochondrial modulator with potential benefits for hepatic function and muscle preservation. Conclusion: Targeting metabolic pathways represents a promising strategy to enhance liver regeneration. Integrating metabolic biomarkers and personalized interventions may improve perioperative outcomes in HCC patients undergoing hepatectomy.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute leukemia; however, the first year after transplantation is associated with an increased risk of morbidity and mortality. This study aimed to evaluate changes in nutritional intake and body composition during the first 100 days following allo-HSCT and to examine their associations with one-year all-cause mortality. In this single-center prospective study, 152 adults scheduled to undergo allo-HSCT were assessed at baseline and on days +30 and +100 after transplantation. Assessments included anthropometric and body-composition measurements, dietary intake evaluation, and nutritional risk screening using the Nutritional Risk Screening 2002 (NRS-2002) tool. The prevalence of nutritional risk increased from 8.6% at baseline to 69.1% on day +30. In the primary analysis, a greater decline in fat-free mass (FFM) was associated with an increased risk of death within one year after transplantation (adjusted HR = 1.04 per 1-kg loss). However, this association was no longer observed in the landmark sensitivity analysis. During the first 100 days following allo-HSCT, nutritional status and body composition deteriorated markedly. A greater decline in FFM was associated with higher one-year mortality in the primary analysis; however, this association was attenuated and was no longer statistically significant in the landmark sensitivity analysis.
BACKGROUND:Sarcopenia is increasingly recognized as a prognostic factor in oncology; however, most studies have focused on static baseline muscle mass in heterogeneous populations. Whether dynamic skeletal muscle loss during systemic therapy carries independent prognostic value, particularly in clinically stable patients with controlled disease, remains unclear. We investigated the prognostic relevance of three-dimensional volumetric muscle assessment in advanced urothelial carcinoma (UC) patients who achieved disease control with first-line platinum-based chemotherapy and subsequently received maintenance therapy. METHODS:This multicenter retrospective study included 82 patients with unresectable or metastatic UC across 10 institutions. Psoas muscle volume (PMV) was quantified using three-dimensional computed tomography (CT) reconstruction. The relative percentage change in PMV during induction chemotherapy (ΔPMV) was calculated as: (PMV at pre-maintenance - PMV at baseline)/PMV at baseline × 100. A predefined PMV loss ≥ 5% (defined as ΔPMV ≤ -5%) was considered clinically significant. Baseline cross-sectional muscle indices, including skeletal muscle index (SMI), total psoas index (TPI), and paraspinal muscle index (PMI), as well as inflammatory and nutritional markers, were evaluated. Overall survival (OS) was analyzed using multivariable Cox regression. RESULTS:During a median follow-up of 19 months, 35 deaths occurred. Baseline cross-sectional muscle indices (SMI, TPI, and PMI) were not associated with OS. In contrast, patients with PMV loss ≥ 5% (ΔPMV ≤ -5%) had significantly shorter OS. In multivariable analysis adjusting for clinical, inflammatory, and nutritional factors, PMV loss ≥ 5% remained independently associated with worse OS (HR 2.14, 95% CI 1.02-4.50, p = 0.044). Dynamic volumetric muscle decline may reflect clinically meaningful physiologic vulnerability despite tumor control. CONCLUSIONS:Dynamic loss of PMV during systemic therapy is a strong independent prognostic marker in advanced UC patients with controlled disease, whereas static baseline muscle indices lack prognostic significance. These findings highlight the clinical importance of preserving skeletal muscle mass during systemic therapy and support further investigation of targeted nutritional or supportive interventions.
Breast cancer remains a major global health challenge, and increasing evidence suggests that high red meat intake may contribute to its burden. However, the magnitude and long-term trends of red meat-attributable breast cancer across major economies remain unclear. This study quantified the breast cancer burden attributable to high red meat intake from 1990 to 2021 and projected trends to 2040 across G20 countries using Global Burden of Disease (GBD) 2021 data. Using GBD 2021 estimates, we assessed red meat-attributable breast cancer burden based on the Comparative Risk Assessment (CRA) framework. Temporal trends were evaluated using estimated annual percentage change (EAPC), and age-period-cohort (APC) and Bayesian APC (BAPC) models were applied to identify cohort patterns and generate projections through 2040. We found a substantial global increase in age-standardized incidence (ASIR), rising from 3.9 to 6.7 per 100,000 between 1990 and 2021. The United States, China, and Japan together contributed nearly 45% of G20-attributable Disability-Adjusted Life Years (DALYs). Trends varied markedly by development level: high Socio-demographic Index (SDI) countries showed declining or stable burdens, whereas low- and middle-SDI countries experienced pronounced increases. Younger cohorts (particularly ages 30-49) exhibited the highest APC-derived risks, indicating a shift toward earlier-onset burden. BAPC projections suggest that red meat-attributable DALYs will continue to rise and may increase by approximately 30%-50% by 2040 if no further interventions are implemented. High red meat intake is a significant and growing contributor to breast cancer burden, with particularly rapid increases in low- and middle-SDI settings and among younger cohorts. Strengthening dietary risk reduction strategies and targeted prevention efforts in G20 countries is essential to mitigate the projected rise in burden over the coming decades.
The associations between dietary factors, whole and refined grains, and colorectal cancer (CRC) remain unclear, particularly in Middle Eastern populations. This multicenter, population-based case-control study assessed the associations between whole and refined grain intake and CRC risk in adults across three provinces in Iran. A total of 402 CRC patients and 825 controls were included. CRC was confirmed by colonoscopy, and dietary intake was assessed using a validated food-frequency questionnaire. Individuals in the highest tertile of whole-grain consumption had a 52% lower risk of CRC compared with those in the lowest tertile (OR: 0.48; 95% CI: 0.32-0.74), whereas individuals in the highest tertile of refined grain intake had 2.62 times higher odds of CRC (OR: 2.62; 95% CI: 1.62-4.24). Dose-response analyses indicated a non-linear inverse association for whole grains, with the greatest risk reduction observed between 50 and 100 g/day. Substitution analyses showed that replacing refined grains with whole grains was associated with a modest reduction in CRC risk (OR: 0.91; 95% CI: 0.85-0.97). These findings suggest that higher whole-grain intake significantly reduces CRC risk, whereas refined-grain consumption substantially increases it, supporting dietary strategies that promote whole-grain intake for CRC prevention.
Indicators of a poorer food environment, such as low food environment index scores, food deserts, and food swamps, have been linked to increased mortality and decreased survival among colorectal cancer (CRC) cases. This retrospective study of 47,807 primary CRC cases from the Kentucky Cancer Registry (KCR) database diagnosed between January 1995 and December 2021 used Cox-proportional-hazard (Cox-PH) regression models to estimate adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for CRC-specific mortality and all-cause mortality associated with residential fast-food exposures. Residential fast-food exposures were not associated with CRC-specific mortality. However, residing within 0.5-mile of a fast-food outlet was associated with a 7% higher hazard of all-cause mortality (aHR: 1.07; 95% CI: 1.02-1.11; P-for trend: 0.001) compared with those living more than 3 miles away. Similar associations for all-cause mortality were observed for higher fast-food coverage (aHR: 1.05; 95% CI: 1.02-1.07; P-value: 0.001) and fast-food density (aHR: 1.05; 95% CI: 1.02-1.07; P-value: 0.001) within a mile radius. Residential fast-food exposures, such as closer proximity, higher fast-food coverage and greater fast-food density, may contribute to a modest increase in all-cause mortality among individuals diagnosed with CRC. These findings underscore the potential role of neighborhood food environments in the survival of CRC patients.
Glioblastoma (GBM) is an aggressive glioma associated with poor prognosis and a median survival of under one year. Standard therapies-surgery, radiotherapy, and temozolomide-impose substantial financial burdens and reduce quality of life, driving interest in less invasive adjunctive approaches. The ketogenic diet (KD) has shown promise by targeting tumor metabolic vulnerabilities, as GBM cells rely heavily on glucose and exhibit limited capacity for ketone metabolism. Although KD is well-validated in epilepsy and diabetic ketoacidosis, its application in GBM yields inconsistent results due to small trials, low adherence, and variability in study designs. Emerging evidence suggests that interindividual differences in gut microbiota (GM) composition may significantly contribute to this inconsistency. GM modulates host metabolism, influences KD efficacy, and exhibits bidirectional interactions with tumor progression. Notably, glioma patients display distinct GM profiles that may alter therapeutic responses. This comprehensive review synthesizes current literature on the interplay between KD and GM in GBM, highlighting mechanisms by which GM variability affects metabolic outcomes. Understanding these interactions is essential to reconcile discrepant findings and optimize patient selection for KD-based interventions, ultimately advancing personalized metabolic strategies in neuro-oncology.
Taste dysfunction is increasingly recognized as a treatment-related adverse effect in pediatric oncology and may contribute to nutritional vulnerability. This prospective longitudinal study evaluated 60 children aged 8-18 years with solid tumors at an early-treatment baseline, defined as within the first month after diagnosis and following completion of the first chemotherapy cycle, and during treatment at months 2 and 4. Twenty healthy peers served as baseline controls. Self-reported taste alterations were assessed using a validated self-report instrument, and gastrointestinal symptoms and nutritional risk were evaluated using standardized scales. Subjective taste alterations increased during therapy, while objective PROP testing indicated progressively reduced bitterness responsiveness. Gastrointestinal symptom burden also increased significantly over time. Nutritional risk scores were positively correlated with both gastrointestinal symptom severity (r = 0.30-0.42, p < 0.05) and taste alteration scores (r = 0.28-0.43, p < 0.05). Children receiving multimodal treatment tended to exhibit more pronounced sensory alterations and higher nutritional risk. These findings suggest that treatment-associated taste changes co-occur with greater gastrointestinal symptom burden and higher nutritional risk in children with solid tumors. Longitudinal assessment of sensory changes may help identify patients at increased nutritional vulnerability during oncological therapy.
This study aimed to evaluate the prognostic significance of preoperative inflammation-based biomarkers, with a particular focus on the Prognostic Nutritional Index (PNI), in predicting recurrence-free survival (RFS) in patients with non-muscle-invasive bladder cancer (NMIBC). We conducted a retrospective analysis of 210 patients with primary NMIBC diagnosed between January 2019 and June 2020. Various inflammatory indices were calculated from preoperative laboratory data, including PNI, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), neutrophil-to-platelet ratio (NPR), and albumin-to-globulin ratio (AGR). The optimal PNI cutoff was determined using receiver operating characteristic (ROC) curve analysis for 2-year recurrence. Univariable and multivariable Cox proportional hazards models were employed to identify independent prognostic factors for RFS. Survival curves were generated using the Kaplan-Meier method and compared with the log-rank test. A restricted cubic spline (RCS) model was used to examine the dose-response relationship between PNI and recurrence risk. The optimal PNI cutoff for recurrence was 47.5, with an area under the curve (AUC) of 0.816. Multivariable analysis identified high pathological grade (adjusted hazard ratio [HR]: 2.57; 95% confidence interval [CI]: 1.37-4.81; p = 0.003) and low PNI (≤47.5) (adjusted HR: 2.40; 95% CI: 1.31-4.40; p = 0.005) as independent risk factors for reduced RFS. PNI exhibited high discriminative performance, and DeLong pairwise comparisons confirmed its AUC was significantly higher than all other evaluated biomarkers (all p < 0.001). Incorporating PNI into the EAU risk model significantly improved model fit (likelihood-ratio test p = 0.008) and increased the C-index from 0.68 to 0.74. Kaplan-Meier analysis confirmed that patients with low PNI had significantly worse RFS than those with high PNI (log-rank p = 0.005). The RCS model revealed a significant linear inverse relationship between PNI and recurrence risk (P for overall association < 0.001; P for nonlinearity = 0.214). These findings suggest that preoperative PNI is a promising biomarker for recurrence risk stratification in NMIBC, with good prognostic discrimination in this cohort, although external validation is required.
Bladder cancer is a major public health concern worldwide. While smoking and occupational exposures are established risk factors, the role of dietary fatty acids (FAs) in bladder cancer risk remains unclear. Data were collected from 711 bladder cancer cases and 3,297 controls in the IROPICAN study (2017-2020) across ten Iranian provinces. Dietary intake was assessed using a validated food frequency questionnaire. Intakes of total fat, saturated FAs (SFAs), monounsaturated FAs (MUFAs), polyunsaturated FAs (PUFAs), and trans FAs (TFAs) were analyzed. Principal component analysis (PCA) identified fatty acid consumption patterns. Multivariable logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounders. PCA suggested that balancing FA intake, specifically increasing omega-3 FAs, moderating omega-6, and reducing saturated fats, was associated with a favorable profile for bladder cancer risk. OR for stearic acid intake was 0.28 (95% CI: 0.12-0.67). Conversely, OR for high intake of palmitoleic acid, alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA) was elevated. Sex-specific effects were found stearic acid was protective in men, while PUFAs were protective in women. No associations were observed for total fat or cholesterol. These results highlight the importance of FA subtypes, rather than total fat intake, in dietary recommendations.
Cancer-associated cachexia (CAC) is common in cervical cancer (CC) patients. This condition affects the Health-related quality of life (HRQL). This study aims to assess the impact of CAC on HRQL, comparing the Quality of Life Questionnaire (QLQ) QLQ-C30/QLQ-CAX24 and the Functional assessment of anorexia/cachexia therapy (FAACT) instruments. A cohort of CC patients answered the QLQ-C30/QLQ-CAX24 and the FAACT instruments between October 2020 and October 2021. The psychometric/clinimetric characteristics of the instruments were compared. 244 CC patients were included in the study. Correlations between scales ranged from 0.008 to 0.81. The summary score of QLQ-C30 correlated well with the FAACT total score (r = 0.684) and the FAACT Physical Well-being subscale (r = 0.81). The correlation with five nutritional parameters and prognostic indices was poor (r < 0.364). Most symptom scales of the QLQ-CAX24 presented a floor effect, and those of the FAACT did not. The Nausea/vomiting score of the QLQ-C30, and the Loss of control and Forced to eat scales of the QLQ-CAX24 were independently associated with overall survival. The QLQ-C30/QLQ-CAX24 and FAACT instruments differ substantially, but some scales are comparable. We propose an algorithm to select the appropriate instrument to asses HRQL for a research protocol.
