Vasculature-induced tumor tissue heterogeneity impedes predicable drug distribution and presents notable challenges for optimizing nanoparticle (NP)-based drug delivery. However, mesoscopic-scale tumor heterogeneity across entire brain remains poorly characterized. To address this, we integrated micro-optical sectioning tomography (MOST) with high-precision three-dimensional (3D) reconstruction analysis to map pathological features of orthotopic glioma at submicron resolution across whole mice brain. Our findings uncovered significant heterogeneity in glioma invasiveness, vasculature, and compensatory angiogenesis while precisely delineating NP distribution throughout the tumor. Notably, early-stage glioma co-opted and migrated 680-micrometer upstream along the main cerebral artery within 4 days after glioma implantation. Blood-brain barrier permeability gradually increased during glioma progression, enabling NP penetrated via large-diameter vessels instead being restricted to capillaries. This work establishes a multiscale, high-resolution, 3D atlas of glioma heterogeneity and NP distribution, and bridges mesoscopic structural complexity to functional drug delivery barriers, advancing strategies to enhance oncotherapy precision in heterogeneous brain tumors.

Geography and geospatial data science hold the potential to make unique contributions to the reduction of the burden of cancer on society. Here we use colorectal cancer (CRC) as an example to show how spatial insights into CRC risk factors and priority areas for screening may be obtained to achieve geographically targeted screening. We obtained data from the UK Biobank and divided the participants into the older (50<=age < 70) and young (age < 50) adult groups. The data consists of 2,080 CRC cases and 8,062 controls. We used a case-control study and geographically weighted logistic regression (GWLR) to explore spatial variations in risk levels of significant factors at a fine geographic resolution. Analysis results reveal that, among all significant risk factors, polygenic risk score (PRS) is the most important risk factor for both age groups. Findings suggest that the top priority screening areas for older adults, using PRS as the sole risk factor, are between Sheffield, Birmingham, Cardiff, Bristol, and west of Greater London. For young adults, the top priority areas are between the south of Glasgow and Edinburgh and northwest of Greater London. Furthermore, the approach used in this study holds promise for developing more effective targeted cancer screening.

As effective melanoma treatments have become available, utilizing isolated limb perfusion (ILP) to treat unresectable melanoma limited to the limb has decreased. However, some patients still receive long-term benefits from ILP. We aimed to identify features of the pretreatment tumor microenvironment (TME) to identify patients who may benefit from ILP. Pretreatment metastatic melanoma samples from 22 patients treated at Helsinki University Hospital with ILP from 2008 to 2018 were analyzed with multiplex immunohistochemistry (mIHC) and digital image analysis. Antibody panels evaluated the proportions of immune cells in the intratumoral and extratumoral compartments. We examined whether treatment response and median progression-free survival (PFS) after ILP correlated to findings in the TME. A statistically significant positive correlation was found between PFS and lower immune cell infiltrations in the intratumoral compartment (CD3+, CD4+, and CD11c+ cells), and increased numbers of immune cells in the extratumoral compartment were associated with longer PFS (CD3+, CD4+, CD8+, all expressing PD-1). Furthermore, the distribution of some immune cell subsets correlated with complete treatment response (PD-1/PD-L1-positive CD4+ and PD-1-positive CD8+ cells). Our results suggest that patients may have a better ILP outcome if the metastases exhibit a lower distribution of specific immune cell subtypes intratumorally and a higher extratumoral distribution of some immune cell subtypes.

Treatment-induced nausea (TIN) is a persistent and distressing symptom among women undergoing breast cancer therapy, despite adherence to antiemetic guidelines. A history of pregnancy-induced nausea and vomiting (PNV) and genetic variations in GDF15, a stress-responsive cytokine, may contribute to nausea susceptibility. The purpose of this study was to understand the relationship between GDF15 variants, history of PNV, and the prediction of TIN severity across the first 6 months following breast cancer surgery.

A prospective, 6-month longitudinal cohort study enrolled 290 women undergoing surgery for early-stage breast cancer. Nausea severity was assessed using a 0-10 numeric rating scale at multiple time points post-surgery and during adjuvant therapy. Saliva samples were genotyped for GDF15 single nucleotide polymorphisms (SNPs) (rs810804, rs1227731, rs8101249, rs1059369). Group-based trajectory modeling (GBTM) identified nausea severity patterns. Associations between GDF15 SNPs, PNV history, and TIN severity were analyzed using multivariate logistic regression.

Three nausea severity trajectories were identified: extremely low (41%), low (47%), and moderate (12%). A history of PNV significantly predicted higher TIN severity (p < 0.05). Additionally, GDF15 SNPs rs8101249 and rs1227731 were associated with TIN severity trajectories. In the final multivariate model, PNV history and rs1227731 remained significant predictors.

PNV history and GDF15 genetic variants influence TIN severity in women undergoing breast cancer treatment. Identifying at-risk patients may improve symptom management. Future research should explore GDF15-targeted interventions to reduce nausea burden.

Osteosarcoma has a global incidence of 3.4 cases per million annually, with 10-20% of patients presenting with metastasis at diagnosis. Its high metastatic potential is attributed to a highly proliferative cell population and cancer stem cells that drive tumorigenesis and metastasis. This study examines the relationship between CD133 and CXCR4 expression and metastasis in osteosarcoma.

Using a cross-sectional approach, blood serum from osteosarcoma patients diagnosed at two centers was analyzed for CD133 and CXCR4 levels via Reed Biotech ELISA KIT. Absorbance quantified marker levels, and metastasis data were obtained from medical records. A chi-square test assessed the relationship between marker levels and metastasis, with significance set at p < 0.05.

Among 40 patients (80% < 40 years), mean CD133 was 0.23 ± 0.02 pg/ml and mean CXCR4 was 6015.82 ± 2345.55 pg/ml. CD133 and CXCR4 levels were significantly associated with metastasis (p = 0.009 and p < 0.001, respectively).

These findings suggest that higher expression of CD133 and CXCR4 correlates with increased metastasis in osteosarcoma, underscoring their potential roles in predicting metastatic behavior and aiding in targeted therapeutic strategies.

It is currently recommended to perform open radical nephroureterectomy (oRNU) with bladder cuff excision in patients with locally advanced (cT3-4 or cN1-2) upper tract urothelial carcinoma (laUTUC). We tested the hypothesis that bladder recurrence-free survival (BRFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) are not influenced by the surgical approach in patients with laUTUC using a large multicenter series.

This was a multicenter retrospective cohort study including 361 patients with preoperative cT3-4 cM0 or cN1-2 cM0 laUTUC treated with open or minimally invasive RNU from 1999 to 2019 at 21 academic centers in Europe, Asia, and the United States. Missing values of relevant baseline characteristics were estimated through multiple imputation of chained equations. Baseline patients' heterogeneity was balanced using a 1:1 propensity score matching estimated using logistic regression. Uni- and multivariable Cox regression analyses for bladder recurrence, metastasis, cancer-specific death and overall death were performed according to clinical and pathological characteristics. Kaplan Meier (KM) estimates and log-rank test were used to compare BRFS, MFS, CSS and OS according to clinical and pathological features.

Median follow-up was 28 months. After propensity score matching, two cohorts of 115 laUTUC patients each with similar baseline and preoperative tumor characteristics were obtained. In the matched cohort, pT ≥ 3 stage was found in 84 (73%) and 67 (58.3%) patients in the oRNU and miRNU groups, respectively. Positive lymph nodes were detected in 27 (23.5%) and 32 (27.8%) patients in the oRNU and miRNU groups, respectively. In the multivariable regression analysis, pT ≥ 3 and positive lymph nodes were associated with an increased risk of metastasis (HR 3.22, 95% CI 1.26-8.23, and HR 4.03, 95% CI 2.05-7.89, respectively). The surgical approach (oRNU vs. mi RNU) did not influence oncological outcomes as shown by uni- and multivariable analyses as well as Kaplan-Meier estimates, regardless of pT stage.

The oncological outcomes of laUTUC for cT3-4 cM0 or cN1-2 cM0 disease are comparable whether RNU is performed via an open or minimally invasive approach. Therefore, the decision to opt for oRNU or miRNU should be guided by the surgeon's expertise and the patient's comorbidities, rather than concerns over long-term oncological outcomes associated with either surgical technique.

Children with cancer frequently experience fatigue that affects their quality of life, yet current management practices remain poorly understood. We aimed to assess health care professionals' (HCPs) knowledge, attitudes, and practices regarding fatigue management in pediatric oncology.

We conducted a cross-sectional, web-based survey of pediatric hematology-oncology HCPs in the United States of America and Canada to assess fatigue education, management practices, barriers to fatigue management, and perspectives on future clinical trials for fatigue.. Quantitative data were analyzed using descriptive statistics, chi-square test, and logistic regression. A framework approach was used to analyze qualitative data from open-ended survey response items.

In total, 528 HCPs completed survey: 49% oncologists, 27% nurses, and 23% nurse practitioners. Only 29% and 32% of HCPs attended educational events on fatigue and screened patients for fatigue primarily through verbal assessments during outpatient settings, respectively. Although 91% of HCPs emphasized importance of assessing fatigue, only 18% were familiar with fatigue management guidelines, and only 1% followed them. Commonly recommended fatigue interventions included sleep hygiene (91%), physical exercise (82%) and rest (78%). Themes for improving fatigue management included enhancing education for HCPs and patients, implementing routine fatigue screening, and disseminating guidelines and fatigue management resources. Barriers to effective fatigue management were insufficient education, lack of routine screening, and limited access to fatigue screening tools. Most HCPs (94%) supported future clinical trials for fatigue management, and 86% preferred these trials to test non-pharmacological interventions for fatigue management.

Most HCPs acknowledge the importance of assessing fatigue, but significant gaps remain in education, routine screening, and guideline implementation. Addressing barriers such as insufficient education and limited access to resources is essential for improving fatigue management practices.

The purpose of this study was to investigate the association between the full spectrum of visual acuity categories and risks of all-cause, cardiovascular disease (CVD)-related, cancer-related mortality in the UK Biobank study.

A total of 131,468 participants (aged 40-79 years) with visual acuity measurement from the UK Biobank prospective cohort were included. Visual acuities of both eyes were used to assign each participant into one of the following groups: bilateral normal, unilateral near normal, bilateral near normal, unilateral visual impairment (VI), mild VI, and low vision. Cox proportional hazards multivariable regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the risks of all-cause, CVD-related, and cancer-related mortality.

Over a median follow-up of 13.49 years, a total of 9372 deaths were recorded, including 4682 cancer-related deaths and 1926 CVD-related deaths. Compared with the bilateral normal group, participants with decreased visual acuity had increased risks of all-cause and CVD-related mortality with dose-response-type gradients, but no elevated risk of cancer-related mortality was observed. Decreased unilateral visual acuity but not bilateral near normal vision was associated with increased risks for all-cause and CVD-related mortality. For all-cause and CVD-related mortality, the adjusted HRs were 1.17 (95% CI = 1.09-1.25) and 1.24 (95% CI = 1.07-1.44) for the unilateral near normal group, and 1.20 (95% CI = 1.14-1.27) and 1.26 (95% CI = 1.12-1.42) for the unilateral VI group.

Decreased unilateral visual acuity was associated with increased all-cause and CVD-related mortality risks among participants without VI in the UK Biobank.

Achieving bilateral vision balance may contribute to reducing the mortality risk of individuals with decreased unilateral visual acuity.

Aim: To investigate the relationships of kidney function with clinical and laboratory parameters in multiple myeloma (MM) patients.

Materials and Methods: A cross-sectional study involved 105 MM patients. Data included clinical manifestations and standard laboratory parameters. Kidney function was assessed via estimated glomerular filtration rate (eGFR), serum creatinine, urea, uric acid (UA), calcium (Ca), and albumin-to-creatinine ratio (ACR). The markers of MM activity and burden included M-protein, beta-2 microglobulin (β2m), albumin, hemoglobin (Hb), lactate dehydrogenase (LDH) and platelets (PLT). Rank biserial correlation assessed associations between symptoms and laboratory parameters. Rank-based canonical correlation analysis (RCCA) explored the multivariate relationship between six kidney function indicators and six MM-related markers.

Results: Common laboratory abnormalities included elevated β2m (90,5 %) and anemia (indicated by low Hb in 52,4 % of patients). Frequent symptoms included bone pain (71,4 %) and weakness (68,6 %). Symptoms like weakness/breathlessness correlated significantly with (β2m, M-protein) and renal impairment (creatinine, ACR, eGFR). RCCA identified one significant canonical correlation (R1=0,497; p=0,013), linking impaired renal function (characterized by low eGFR, high ACR, creatinine and urea) with a myeloma profile indicative of disease activity and burden (high β2m, low Hb, low albumin, and high M-protein).

Conclusions: The study confirms a significant multivariate association between a profile of impaired renal function and markers reflecting MM activity, hematopoietic suppression and systemic burden. These findings underscore the multifactorial nature of MM-related kidney injury and highlight the clinical utility of monitoring key laboratory markers (including eGFR, ACR, creatinine, β2m, Hb and albumin) alongside clinical evaluation for comprehensive assessment and management of MM patients.

Restorative proctocolectomy (RPC) is a common surgical indication to manage familial adenomatous polyposis (FAP) patients.

We compared outcomes after ileostomy closure in patients undergoing laparoscopic (LAP) or conventional (OPEN) RPC at one single institution.

Charts from FAP patients (1997-2013) were reviewed. Demographic data (age, sex, previous surgery) and surgical outcomes (original surgical approach, early and late morbidity, complications and reoperations after ileostomy closure) were compared.

A total of 84 patients (53 women and 31 men) submitted to ileostomy closure at a mean age of 30.6 years (11-64) were analyzed. Twenty-one (25%) and 63 patients (75%) formed the OPEN and LAP groups, respectively. Demographic features were similar. After pouch construction, 27 early (32.1%) and 8 late (9.5%) complications occurred, with no mortality. Although overall morbidity rates were similar between both approaches, late complications rate were less common in LAP patients (7.9% x 14.2%). After ileostomy closure, complications were registered in 6 (7.1%) patients, and patients previously operated with the LAP approach also presented less complications (4.7% x 14.2%) and reoperations (3.1% x 9.5%). Additionally, the need for surgical management of complications was greater in the OPEN (9.5%) than the LAP group (3.1%). Besides these numbers, analysis didn't reveal statistical differences among both groups.

In the conditions of the present manuscript, the abdominal approach used for restorative proctocolectomy doesn't seem to decisively influence outcomes after loop ileostomy reversal. In the future, analysis of a greater number of patients may probably demonstrate an expected greater complication and reoperation rates in those previously treated through OPEN procedures.

• Ileostomy closure is an important part of the surgical treatment of FAP patients undergoing restorative proctocolectomy by any approach.

• Complication rates after loop ileostomy reversal occurred in 7% of a group of 84 FAP patients.

• Among those operated with the laparoscopic approach, complications (4.7% x 14.2%) an reoperations (3.15% X .5%) were less common when compared to the group treated with conventional approach.

• In the future, annalysis of a greater number of patients may probably reveal an statistical difference between these numbers, thus clearly demonstrating this great advantage of minimally invasive procedures in this group of patients.