Gene fusions exist with low prevalence in colorectal cancer (CRC), and the clinical utility of fusion testing in advanced CRC remains unclear. We sought to identify oncogenic fusions in patients with advanced CRC using a fusion partner-agnostic circulating tumor DNA (ctDNA) assay to better understand their clinical relevance.

We performed a retrospective analysis using de-identified data from 18,558 patients with advanced CRC who underwent ctDNA next-generation sequencing with Guardant360^® from 2017 to 2022. These samples were subsequently reanalyzed with a partner-agnostic bioinformatics method to identify both clonal and non-clonal fusions. We analyzed for associations between fusions and MSI-H status, as well prior EGFR-directed therapy signature.

Fusions were identified in 221 (1.3%) of CRC patients analyzed. 193 patients had 258 activating fusions, while 28 patients had fusions of uncertain significance. Among patients with activating fusions, there were 18 clonal fusions (7%) and 240 (93%) subclonal fusions. Clonal fusions were more common in patients with MSI-H status, and subclonal fusions were associated with prior EGFR exposure signature.

Among patients with advanced CRC, partner-agnostic ctDNA fusion detection is possible and improves identification as a blood-based approach by extension of fusion calling partners. Detection of fusions in the ctDNA may provide rationale for potential therapeutic strategies according to clonality as informed by the ctDNA, whereas subclonal fusions may play a role in acquired resistance to EGFR inhibitors in KRAS/NRAS/BRAF^wild-type tumors.

This study examines the global burden of colorectal cancer (CRC) attributable to diet low in milk among middle-aged and elderly populations from 1990 to 2021 and projects future trends to 2050.

Data from the Global Burden of Disease (GBD) 2021 study were obtained via the Global Health Data Exchange. The burden was assessed using number of cases and rates of Disability-Adjusted Life Years (DALY) and death, stratified by age, sex, region, nation, and Socio-Demographic Index (SDI). Temporal trends were analyzed using estimated annual percentage change (EAPC), and future trends were projected using the Bayesian Age-Period-Cohort (BAPC) model.

In 2021, the global DALY and death cases of CRC attributable to a diet low in milk among middle-aged and elderly populations was 2.71 million and 0.14 million, respectively, representing increases of 92.81% and 103.02% from 1990. However, the corresponding DALY and death rates decreased from 209.65 to 182.64 per 100,000 population and from 9.96 to 9.13 per 100,000 population, respectively, with EAPCs of - 0.54 and - 0.36. The DALY and death rates rise with age, peaking in the 95 + age group. From 1990 to 2021, among regions, Southern Sub-Saharan Africa and Eastern Europe saw the largest increases in these rates, while Australasia, High-income North America, and Western Europe had the largest decreases. At the national level, Lesotho, Cabo Verde, and Georgia saw the largest increases in the DALY and death rates, while Austria, Australia, and Germany experienced the largest decreases. The correlation analysis showed that the DALY and death rates across 21 regions increased with rising SDI levels up to approximately 0.67, then declined and stabilized. Projections suggest a significant rise in DALY and death cases, with a slight increase in DALY and death rates.

The burden of CRC attributable to a diet low in milk remains substantial among middle-aged and elderly populations globally, with significant age, sex, regional and national disparities. These findings highlight the need for targeted dietary interventions to mitigate the growing burden of CRC among middle-aged and elderly populations.

Distant metastasis remains the leading cause of mortality in breast cancer, yet comprehensive population-based evaluations of metastatic site combinations and their survival implications are limited. This study aimed to explore the clinicopathological determinants and prognostic outcomes of site-specific and multi-organ metastases in breast cancer using SEER data. A total of 200,558 female breast cancer patients diagnosed between 2014 and 2023 were extracted from the SEER database. Logistic regression was used to assess associations between clinicopathological features and metastatic patterns. Kaplan-Meier analysis and Cox proportional hazards models were applied to evaluate overall survival (OS) across different metastatic site combinations. Among patients with distant metastasis classified into 15 common metastatic patterns, bone was the most common metastatic site (21.3%), followed by lung (16.1%), liver (9.2%), and brain (2.9%). Molecular subtypes showed distinct organotropism: HR+/HER2 - tumors were prone to bone-only metastasis, whereas HER2-positive and triple-negative subtypes were more likely to involve visceral and brain metastases. Multi-organ metastases, especially combinations including the brain (e.g., brain + liver + lung), were associated with the poorest prognosis (median OS: 4.0 months). Younger age (≤ 40 years), higher histological grade (Grade III), and tumor location in the axillary tail or unspecified regions were independently associated with increased metastatic risk. Grade III tumors exhibited broader visceral spread and significantly worse survival compared to lower-grade tumors. This is the first population-based study to systematically characterize 15 metastatic site combinations and their survival outcomes across molecular subtypes. The findings highlight the heterogeneity of breast cancer metastasis and underscore the need for subtype-specific, site-targeted surveillance strategies and prognostic assessment tools.

Background It is crucial to identify the high-risk factors associated with the recurrence and metastasis of endometrial cancer (EC) in order to implement more precise clinical stratification and management strategies for EC patients. Methods A total of 336 patients with stage I-III EC were retrospectively analyzed. According to the recurrence site, they were divided into locoregional recurrence (LR) and poor-prognosis recurrence (PPR). The factors that may affect the prognosis of EC were analyzed and the subgroups were analyzed. Results Among the no recurrence (NR), LR and PPR groups, 5-year OS were 89.4%, 60.2% and 46.8%, 5-year RFS were 100%, 15.4% and 6.4%. The FIGO stage, molecular classification, lymphovascular space invasion (LVSI) and smoking history were independent risk factors affecting 5-year OS and 5-year RFS in EC patients (p < 0.05). Pathological type and progesterone receptor (PR) were independent risk factors affecting 5-year OS (p < 0.05). Histologic Grade and adjuvant therapy were independent risk factors affecting 5-year RFS (p < 0.05). Myometrial invasion, LVSI and FIGO stage were independent risk factors in the LR subgroup (p < 0.05), FIGO stage, ER and PR were independent risk in the PPR subgroup (p < 0.05). Conclusions Patients with myometrial invasion ≥ 1/2 and substantial LVSI may be more likely to have LR, while patients with positive ER and PR are more likely to have PPR. We need to pay attention to these factors to help us judge the prognosis of EC patients.

The overall prognosis of stage IV gastric cancer (GC) is poor. Large-scale and high-quality evidence on the role of conversion surgery (CS) is limited. This study aims to compare the long-term survival and morbidity in stage IV GC between systemic treatment followed by CS vs systemic treatment only (i.e. no CS).

A systematic search was performed on PubMed, Embase, Scopus, and Cochrane Library till September 2024. The inclusion criteria were patients with stage IV GC who received systemic chemotherapy + / - immunotherapy/other adjunct therapies. Pooled hazard ratio was calculated to compare survival between CS and no CS, and various subgroup analyses were performed.

There were 36 studies with 3177 patients (CS n = 1273, no CS = 1904) included, consisting of 29 retrospective cohort studies, 6 prospective non-randomized trials, and 1 retrospective case series. The most commonly used chemotherapy regimen (n = 10 studies) was S-1 + cisplatin. The median OS range was 14.4-60.0 months and 4.7-19.9 months in the CS and no CS groups, respectively. Pooled OS (n = 2826 patients, HR 0.36, 95% CI: 0.32-0.40) and PFS (n = 609 patients, HR 0.38, 95% CI: 0.31-0.46) were superior in CS compared to no CS. Overall incidence of anastomotic leak, intra-abdominal abscess, and post-operative bleeding following CS were 5.4%, 3.6%, and 2.0%, respectively.

Survival in patients with stage IV GC is superior with CS following systemic treatment compared to systemic treatment alone, but however, quality of evidence is low considering the predominant inclusion of retrospective studies and heterogeneous selection criteria for CS which may favour those with good tumour biology.

Observational studies found that phosphodiesterase 5 (PDE5) inhibitors use is linked to both increased and decreased risk of cancer; while the causal relationship remains unclear. To clarify whether PDE5 inhibitors medication may affect the risk of cancer, 2-sample cis-Mendelian randomisation (MR) analysis was therefore performed. Uncorrelated (linkage disequilibrium [LD] r² < 0.001) single-nucleotide polymorphisms (SNPs) in PDE5A gene associated (P < 5.0 × 10^-8) with circulating levels of PDE5A protein identified from UKB-PPP were used as genetic instrument to mimic the action of PDE5 inhibition. Summary-level data for 22 types of cancer obtained from site-specific GWAS were analyzed in discovery stage (428,361 cancer cases) and then replicated in the FinnGen study (87,505 cancer cases). Inverse-variance weighted random-effects models were used as primary analysis. After multiple testing correction, genetically predicted, per-standard deviation (SD) decrease in PDE5A protein was associated with decreased risk of colorectal cancer with a pooled odds ratio (OR) of 0.80 (95% confidence interval [CI]: 0.75-0.86; P = 6.15 × 10^-11). A significant MR association (OR = 0.48, 95% CI: 0.34-0.68; P = 4.70 × 10^-5) with gastric cancer (GC) was also observed in combined analysis. There was little evidence to support associations between genetically proxied PDE5 inhibition and other 20 studied cancers. We found an protective effect of genetically proxied PDE5 inhibition on CRC and GC risk. Our drug target MR analyses provide genetic evidence in predicting long-term safety profiles of PDE5 inhibitors on cancer risk and highlight the potential of drug repurposing in CRC and GC.

Robotic-assisted radical laparoscopic prostatectomy (RARP) is a standard treatment for localized prostate cancer. While surgical factors are often considered, the impact of anesthesiological factors, particularly intraoperative fluid management, on postoperative outcomes remains understudied. This study aimed to evaluate the relationship between fluid management and early complications after RARP. The study retrospectively analyzed data from 285 patients who underwent RARP at a single institution between 2019 and 2021. Fluid administration was quantified as corrected fluid dosage (mL/kg/h) and total fluid balance. Postoperative complications within 30 days, including anastomotic leakage and lymphocele formation, were assessed. Multivariable modeling and propensity score matching were used to evaluate the association between fluid management and lymphoceles. We found no significant association between fluid management and major complications (Clavien-Dindo grade ≥ II) or anastomotic leakage. However, a significant association was observed between higher fluid administration and lymphocele formation (p < 0.001). In the generalized linear model, the association of fluid dosage with lymphocele occurrence was confirmed (p = 0.002), independently of a peritoneal flap procedure. At a fluid dosage threshold of 7.73 ml/kg/h, propensity score matching confirmed the association. While major complications following RAPR are rare, generous fluid management was associated with a higher incidence of lymphocele formation. While these mostly remained asymptomatic, this finding suggests that intraoperative fluid management is a modifiable risk factor for lymphoceles and may prevent symptomatic lymphoceles as major complications in larger collectives. Moreover, it provides new insights into their potential pathogenesis.

Cancer is a life-threatening disease that can attack humans at any part of the body as a consequence of abnormal cell growth and proliferation, leading to tumors that can be fatal. Breast cancer is one of the deadliest ailments in the world after lung cancer. Through hormonal and genetic changes that occur in DNA, breast cancer can affect women. The quantitative structural-property relationship (QSPR) is used to provide a comprehensive study of 16 drugs involved in the treatment of breast cancer. According to their chemical structure, the drugs being studied are modeled as molecular graphs. The purpose of this study is to examine the utility of new entire neighborhood topological indices in characterizing the physicochemical properties of a range of breast cancer drugs. Cubic regression analysis was initially employed, followed by multiple linear regression modeling to enhance the correlation between the entire neighborhood topological indices and some properties of the aforementioned drugs. The analysis results are presented and discussed, leading to conclusions about the potential of these new indices for pharmaceutical and chemical research on breast cancer treatments.

As the main undertakers of home care for urostomy patients after discharge, family caregivers play an important role in patients' postoperative recovery. Family caregivers of patients with urostomy may be under greater pressure than patients themselves, and there is a heavy burden on caregivers, and their care needs are complicated and urgent. However, there is a lack of research on the care needs of family caregivers of bladder cancer patients with urostomy, and tools to assess the specific needs of family caregivers of bladder cancer patients with urostomy are lacking. This study aimed to develop an assessment tool to measure the specific needs of family caregivers for bladder cancer patients with urinary ostomies and to examine its reliability and validity. The development of the scale is based on the Supportive Care Framework, and the item pool is determined through literature retrieval and qualitative research. The items of the scale were revised via Delphi expert consultation, and 198 family caregivers of urostomy patients in five 3 A hospitals in Taiyuan City, China, were investigated. SPSS 26.0 and AMOS 22.0 were used for data analysis. Exploratory factor analysis and confirmatory factor analysis were carried out to evaluate the reliability, content validity, discrimination validity, structure validity, and convergence validity of the scale. Exploratory factor analysis identified three dimensions of the 21-item scale of care needs of family caregivers of patients with bladder cancer undergoing urostomy, namely, demand for disease information, demand for physical and mental comfort, and demand for social support. Cronbach's α coefficient and half-reliability of the whole scale and each dimension are greater than 0.7, indicating high internal consistency. Confirmatory factor analysis shows that the scale fits the data well, and the content validity, discrimination validity, and convergence validity of the scale are excellent, which provides evidence of support. The scale developed by the authors is a relatively reliable and effective tool for evaluating the specific care needs of family caregivers of patients with bladder cancer undergoing urostomy. Future research could develop role-specific subscales tailored to distinct kinship categories (e.g., spouses, daughters, sons) to enable precision assessment of caregiving needs.

Adult T-cell leukemia/lymphoma develops decades after Human T-lymphotropic virus type 1 (HTLV-1) infection. Factors like proviral load (PVL), soluble interleukin-2 receptors (sIL-2R), and clonality are associated with its pathogenesis. However, a comprehensive assessment using multiple factors of ATL development and progression based on flow cytometry (HAS-Flow) has not been performed. We conducted a 10-year clinical follow-up of 160 asymptomatic people living with HTLV-1 using HAS-Flow, PVL, sIL-2R, and the HTLV-1 integration site identification. The cases were classified into three groups based on cell adhesion molecule 1 (CADM1)-expressing cells by HAS-Flow: Group 1 (≤ 10%, 115 cases), Group 2 (> 10% to ≤ 25%, 33 cases), and Group 3 (> 25%, 12 cases). In the follow-up, no cases in Group 1 developed ATL, while five cases in Group 2 and nine in Group 3 did. Among the developed ATL, one case in Group 2 and six in Group 3 progressed to aggressive ATL. Higher CADM1-expressing cells and sIL-2R levels were linked to earlier ATL development. The HTLV-1 integration site was identified in all aggressive ATL cases. Thus, evaluating CADM1-expressing cells by HAS-Flow, assessing sIL-2R, and identifying the HTLV-1 integration site can better predict ATL development and progression to aggressive ATL.