While somatic mitochondrial dysfunction occurs in diverse cancers, the association between oncogenesis and germline mitochondrial gene pathogenic variants remains unclear. Further, few clinical observations have been reported of cancer occurring in primary mitochondrial disease (PMD) patients. To improve understanding of the potential modulating role for PMD gene disorders in cancer prevalence. 727 individuals, including 100 with PMD, from 97 unrelated families were retrospectively surveyed to assess their history of individual cancer occurrence. We evaluated survey responses by characterizing the cancer prevalence among the study cohort and comparing to the general U.S. population via the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database. Odds ratio calculation was performed to determine the association of survey responses and cancer prevalence. Although overall cancer prevalence in PMD probands and their families was elevated compared to the NCI SEER rate (8800 vs 5600 cases per 100,000), odds ratio calculation determined that PMD did not significantly increase the likelihood of developing cancer, with a non-significant trend observed toward less cancer occuring in PMD that needs to be explored in further studies. Cancer prevalence was significantly correlated with advanced age. Significantly reduced prevalence of prostate cancer was seen across the entire cohort. Surprisingly, while low absolute prevalence (n = 3), a 9-fold increased odds ratio of cancer was seen in POLG patients relative to those with other causes of PMD. No evidence of increased cancer odds was identified in a cohort of PMD patients and their close relatives. Interestingly, a possible inverse association, which did not reach statistical significance, was suggested between mitochondrial disease status and cancer odds. Future prospective investigations in larger PMD kindreds are warranted to validate and evaluate potential mechanistic relations between cancer prevalence and PMD. No increased odds ratio but rather a non-significant trend toward inverse relationship between cancer and primary mitochondrial disease was observed in a retrospective cohort survey study, based on which future studies are warranted. Mitochondria are key organelles in our cells that make energy, help control cell death, and regulate the production of reactive oxygen species. Because of these roles, scientists have long suspected that mitochondrial dysfunction might influence cancer development. Tumors often show abnormal mitochondrial activity, but it is unknown whether people who are born with inherited mitochondrial disorders—called primary mitochondrial diseases (PMD)—are more or less likely to develop cancer. PMD includes many different inherited conditions caused by gene changes in either mitochondrial or nuclear DNA. Although cancer cells often acquire mitochondrial mutations, inherited mitochondrial gene changes that impair mitochondrial energy production in the respiratory chain have not been shown to strongly increase cancer odds. To explore this question, we collected health information from 727 individuals across 97 families, including 100 people with PMD. We compared how often cancer occurred in these families to cancer rates from the National Cancer Institute. We also observed whether having PMD, carrying a PMD disease gene variant, or relation to someone with PMD affected a person’s likelihood of developing cancer. A higher overall cancer prevalence was seen in PMD families compared to the general population that appeared attributable to advanced age, as older adults had higher cancer rates regardless of PMD status. Importantly, PMD status did not increase the likelihood of developing cancer. Rather a non-significant trend was observed toward a negative association. One surprising exception was that individuals with POLG-related PMD showed a higher odds ratio of cancer compared to those with other PMD types, although the affected patient number was small and absolute prevalence remained low. Collectively, these results did not reveal a statistically significant association between primary mitochondrial disease and cancer prevalence. Larger studies are needed to confirm these findings and understand whether and how inherited mitochondrial dysfunction might influence cancer development.
Ovarian cancer is the eighth most common cancer among women and an important cause of cancer-related mortality, particularly in high-income countries. Scientific studies show that hypertension may play a significant role in the initiation of cancer. Therefore, we conducted the first meta-analysis to comprehensively examine the association between hypertension and ovarian cancer risk. We performed a literature search of all of the observational studies published as original articles from inception to July 2024, and we searched the following electronic databases: PubMed, Embase, and Cochrane Library. Finally, we included ten full-text cohort and case-control studies addressing the effect of hypertension on ovarian cancer in this meta-analysis. Our study was preregistered with International Prospective Register of Systematic Reviews (PROSPERO CRD42024565574) and followed the PRISMA statement. Effect size was presented as risk ratios (RRs) and 95% confidence intervals (CIs). Heterogeneity test evaluation was performed using Cochran's Q test and I 2 statistics. The meta-analysis included a total of 2,497,898 women. There was a statistically significant association (RR = 1.10, 95% CI: 1.02-1.23, p < 0.011) between hypertension and ovarian cancer risk. Subgroup analysis showed that parity may significantly reduce the ovarian cancer risk, which was higher among women who had never given birth (RR = 1.43, p < 0.0025), while a body mass index (BMI) > 25 kg/m2 increased the risk of ovarian cancer (RR = 1.12, p < 0.0001). The findings of this comprehensive review and meta-analysis indicate that hypertension is associated with higher overall risk of ovarian cancer. While the present data provide novel evidence, further prospective studies are needed to elucidate the association between hypertension and ovarian cancer risk.
Gastric cancer (GC) remains a leading cause of mortality in Vietnam, where distant metastasis is frequently present at diagnosis. Since accessible biomarkers are scarce, we evaluated the association of Neutrophil-to-Lymphocyte Ratio (NLR) and Platelet-to-Lymphocyte Ratio (PLR) with distant metastasis in a Vietnamese cohort to develop a model for patient stratification. This retrospective study analyzed 114 patients, categorizing into metastatic (Stage IV) and non-metastatic groups per AJCC 8th criteria. The optimal cutoffs were determined using receiver operating characteristic (ROC) curve analysis. The diagnostic efficacy between models was compared by DeLong's test. LASSO regression was employed to identify stable indicators. A multivariable logistic regression model was constructed, and its performance was evaluated using 1,000 bootstrap resamples. Clinical utility was assessed via Decision Curve Analysis (DCA). Distant metastasis was 44.7% of cases. Optimal cutoffs of 2.0 for NLR and 181.5 for PLR were identified. Both markers were significantly higher in metastatic group and positively correlated with disease progression. LASSO identified PLR, NLR, and tumor location as the most robust determinants. In multivariable analysis, only multiple tumor location and high PLR remained independent prognostic factors. The combined model integrating clinical factors with NLR and PLR significantly outperformed clinical features alone (AUC: 0.766 vs. 0.619, p=0.0036), with an optimism-corrected C-index of 0.708. At a 0.586 threshold, the model achieved 82.5% specificity and 62.7% sensitivity, supporting a conservative "rule-out" strategy. Calibration slope was 0.659. DCA demonstrated superior net benefit across a 15%-90% risk range; specifically, at a 40% threshold, model spared 19 per 100 patients from unnecessary intervention. This study establishes the first baseline for NLR and PLR in the Vietnamese cohort, showing an association of these biomarkers with GC distant metastasis. A model integrating PLR, NLR and tumor location optimizes patient stratification and resource allocation in resource-constrained healthcare environments. Gastric cancer (stomach cancer) is a leading cause of cancer-related deaths worldwide. In Vietnam, many patients are diagnosed only after the cancer has already spread to distant parts of the body (metastasis). When cancer spreads, it becomes much harder to treat. Doctors need affordable and reliable ways to identify which patients are at a higher risk of metastasis to improve how they manage the disease. Researchers studied 114 gastric cancer patients at the Ho Chi Minh City Oncology Hospital. They looked at two specific markers found in routine, inexpensive blood tests: the Neutrophil-to-Lymphocyte Ratio (NLR) and the Platelet-to-Lymphocyte Ratio (PLR). These markers measure the balance of different white blood cells and platelets, which partially reflect the body’s “inflammation” levels in response to a tumor. The study found that patients with advanced, metastatic cancer had significantly higher NLR and PLR levels compared to those in earlier stages. By combining these blood markers with other clinical information—such as the patient’s and tumor’s data —the researchers created a diagnostic model. This combined model was much more accurate at identifying patients with distant metastasis than using clinical information alone. Because these blood tests are simple, low-cost, and already widely available in hospitals, they offer a practical way for doctors to monitor cancer progression. Using the NLR and PLR ratios can help healthcare providers in Vietnam and elsewhere better identify high-risk patients and personalize their treatment plans more effectively.
The association between hypertension and the incidence of colorectal cancer remains controversial. This study aimed to clarify this relationship in a Japanese population using two large-scale cohort datasets. We conducted a population-based retrospective cohort study using the Shizuoka Kokuho Database, which contains insurance claims from the Shizuoka region and medical checkup data collected between 2012 and 2022. Propensity score matching was used to compare colorectal cancer incidence between normotensive and hypertensive groups, and cumulative incidence was analyzed using Gray's test, with death treated as a competing risk. Among individuals not taking antihypertensive medications, the normotensive and hypertensive group included 113,724 and 85,399 individuals, respectively. During the follow-up period (median, 4.38 years), colorectal cancer developed in 1130 individuals in the normotensive group and 850 in the hypertensive group. After propensity score matching, colorectal cancer incidence was significantly higher in the hypertensive group, with a hazard ratio of 1.15 (95% confidence interval, 1.02-1.30). This association was observed in men. Among individuals taking antihypertensive medications, an increased risk of colorectal cancer was observed in women. To evaluate whether genetically determined susceptibility to hypertension influences colorectal cancer incidence, we additionally analyzed polygenic risk score for blood pressure using a separate Japanese prospective cohort (Japan Multi-Institutional Collaborative Cohort). No positive association between polygenic risk score for blood pressure and colorectal cancer incidence was identified. This discordance between epidemiological findings and genetic analysis warrants careful interpretation, including, but not limited to, the possibility of previously unrecognized environmental factors shared by colorectal cancer and hypertension.
International guidelines recommend fertility counseling at diagnosis for all women with cancer of child-bearing potential, yet whether gestational surrogacy (GS) is included in such counseling is not clear, nor is whether and what proportion of survivors are aware of GS. We assessed the counseling and use of GS, and predictors of oncologist-provided GS counseling among female cancer survivors. A survey on fertility and GS counseling was distributed via national advocacy organizations (April-November 2024). Descriptive statistics and logistic regression evaluated predictors of GS counseling. A total of 519 participants were included. Median age at diagnosis was 32. Most participants had breast (61.5%) or hematologic (14.5%) cancers; 58.2% of participants learned about GS at diagnosis, most often from non-clinical sources (73.2%), including internet/social media (46.0%). Among those aware of GS at diagnosis (n = 302), 134 (44.5%) considered it. Of these, 20 (14.9%) pursued GS, and 16 (80%) ultimately had a child using GS. Commonly cited barriers included cost (45.3%), not ready to build a family (41.4%), and preference to carry the pregnancy (29.9%). While 82.1% remembered receiving counseling on fertility risk, 18.7% recalled GS being included in the conversation. Younger patients without children and those with gynecologic cancers were more likely to receive oncologist-led GS counseling. Fewer than one in five survivors recalled GS counseling from their oncologist at diagnosis, with most learning from non-clinical sources. Predictors of oncologist-led GS counseling included younger current age, having no children, and gynecologic cancers. These findings highlight the need for improved family-building counseling at cancer diagnosis, including GS.
This study aimed to identify germline pathogenic/likely pathogenic variants in DNA damage repair genes associated with increased cancer risk in Korean patients with biliary tract cancer and characterize their population-specific patterns. In this retrospective multicenter cohort study, we performed germline whole-exome sequencing in 172 Korean patients diagnosed with intrahepatic cholangiocarcinoma (n = 83) or gallbladder cancer (n = 89) between June 2001 and February 2022. Germline variants were analyzed in 210 hereditary cancer genes, and the germline landscape of this cohort was compared with that of global cohorts. Pathogenic/likely pathogenic variants were identified in 24 of 172 (14.0%) patients, predominantly in DNA damage repair genes (18 of 24 [75.0%]). BRCA2 was among the most frequently altered genes, harboring two distinct pathogenic variants (2 of 24 [8.3%]; both cases of intrahepatic cholangiocarcinoma). Of the 24 carriers, five (20.8%) harbored Tier 1-2 variants of potential, tumor-confirmation-dependent therapeutic relevance. Notably, 15 of 24 (62.5%) carriers reported no family cancer history. In population-stratified comparisons across nine biliary tract cancer cohorts (n = 4,018), PMS2 showed a Korean-enriched signal after accounting for heterogeneous gene coverage, whereas TP53 showed only a directional, non-significant increase after multiple-testing correction. The study findings provide reference data for genetic counseling in East Asian patients with biliary tract cancer and suggest that germline testing may warrant consideration regardless of family history.
As survival after gastric and esophageal cancer continues to improve, sustained work participation has become an important survivorship outcome. We aimed to evaluate return-to-work (RTW) rates 18 months after curative-intent surgery for gastric and esophageal cancers and to identify clinical and socioeconomic factors associated with delayed or failed RTW. This multicenter, longitudinal, prospective cohort study evaluated working-age Japanese patients undergoing curative-intent surgery for gastric or esophageal cancer. Working status was assessed preoperatively and at 6, 12, and 18 months postoperatively. The primary outcome was working status at 18 months. Secondary outcomes included time to first RTW, and factors associated with non-working and delayed RTW. Exploratory analyses evaluated 6-month patient-reported outcomes (QLQ-C30) and postoperative weight loss. Among 158 eligible patients, 124 (78.5%) were working at 18 months. Older age (≥ 65 years) and pathological stage≥ III were associated with non-working at 18 months, whereas sedentary work and self-employment were associated with a lower risk of non-working. Postoperative appetite loss, financial difficulties (QLQ-C30), and ≥ 10% body weight loss at 6 months were associated with non-working status. Median time to first RTW was 30 and 70 days for gastric and esophageal cancers, respectively. Esophageal cancer and advanced stage were consistently associated with delayed RTW, with weaker evidence for associations with female sex and preoperative retirement. Approximately 80% of patients were working at 18 months after surgery. Postoperative nutritional impairment and symptom burden were associated with long-term work participation and may help identify patients at risk of not working after surgery.
Young age is an independent risk factor for the development of breast cancer brain metastases (BM). Prior work showed that 17β-estradiol (E2), the predominant premenopausal hormone, promotes BM of tumors intrinsically unresponsive to E2, in part through modulating estrogen receptor-alpha expressing (ERα⁺) glial cells. However, how E2 reshapes the brain tumor microenvironment (TME), particularly microglia‑mediated immunity, and its impact to BM progression remains unclear. scRNA sequencing and multiparametric flow cytometry were used to define the impact of E2 and E2-suppression on brain immune-cell populations across different stages of BM progression using spontaneous and experimental models of BM. Depletion of microglia and T-cell co-cultures were used to study microglia's role in E2-induced BM. The effects of E2-suppression alone or in combination with whole brain radiotherapy were tested in preclinical models mimicking late-stage BM. E2 repressed immune surveillance and immune activation programs in microglia from early to late stages of brain metastatic progression, suppressing recruitment of effector immune cells to BM. Estrogen suppression, in turn reactivated anti-tumoral signaling in microglia and increased recruitment of effector immune cells to the brain. Microglia from E2-treated BM-bearing mice showed a reduced capacity to promote T-cell expansion, effector potential, and CD8⁺T cell-mediated tumor cell killing. Conversely, E2-suppression reactivated an effective anti-tumoral response and synergized with RT to significantly decrease BM progression. These findings reveal a previously unrecognized mechanism by which E2 accelerates BC‑BM progression through microglial immunosuppression and support evaluation of endocrine therapies as adjunct treatments for ER⁻ breast cancer brain metastases. Brain metastases from breast cancer are especially common in younger women, but the reasons why are unclear. This study investigated how the hormone estrogen (E2) influences the brain’s immune environment during metastasis. We found that E2 suppresses microglia-the brain’s immune sentinels-and limits the activity and recruitment of cancer‑fighting T cells. Removing or blocking E2 restored microglial defenses, increased immune cell entry into the brain, and improved the effectiveness of radiation therapy. These findings show that estrogen helps create a brain environment that supports tumor growth and suggest that blocking estrogen may improve treatment even for estrogen-receptor-negative breast cancers.
Pain is among the most prevalent and distressing symptoms in advanced cancer, impairing physical, emotional, and social well-being. Management often requires support from family caregivers, whose own health and psychological well-being may also be adversely affected. This study examined the potential utility of digital phenotyping-moment-to-moment quantification of individual-level human behavior-to assess pain and physical quality of life (QOL) in patients with advanced cancer and their family caregivers. Patients with advanced cancer (n = 14) and their caregivers (n = 32) installed the Beiwe smartphone application, which enabled passive GPS data collection over 24 weeks. Raw GPS data were processed into daily mobility features and aggregated using biweekly moving averages and variability measures. Participants completed PROMIS measures of pain (intensity and interference) and physical QOL every 6 weeks. Within-person regression models were used to examine associations between changes in passive mobility features and changes in outcomes, with adjusted R² interpreted as effect size (small = 0.02, medium = 0.13, large = 0.26). Caregiver GPS-derived mobility features predicted a large proportion of variance in patient pain intensity (R² = 0.31) and pain interference (R² = 0.32). Combined caregiver and patient mobility data predicted large variance in caregiver physical QOL (R² = 0.43) and medium-to-large variance in patient pain intensity (R² = 0.16) and pain interference (R² = 0.33). Patient mobility features alone predicted small variance in caregiver physical QOL (R² = 0.02). When examining patient data predicting patient outcomes, mobility features were associated with small variance in physical QOL (R² = 0.03), pain intensity (R² = 0.05), and pain interference (R² = 0.08). These findings suggest that digital phenotyping may be a useful approach for predicting pain and physical QOL in advanced cancer, particularly when incorporating both patient and caregiver data. Further research is warranted to evaluate digital phenotyping as a novel method for monitoring symptoms and functional outcomes in advanced cancer care.
Purpose To develop and evaluate a new deep learning-based risk model that explicitly captures bilateral and longitudinal asymmetries on sequential mammograms for predicting breast cancer risk. Materials and Methods In this institutional review board (IRB)-approved retrospective case-control study, the images of sequential mammographic examinations (at least two per patient with interexamination intervals of 12-36 months)-all of which were acquired on Hologic systems-were extracted from the CSAW-CC dataset (406 cancer patients, 6,053 controls) and an independent dataset (293 cancer patients, 297 controls). A novel model, STA-Risk, whose architecture incorporates side encoding, temporal encoding, and customized asymmetry loss, was constructed using these data. Fivefold cross-validation with the individual datasets and joint training with a mixed dataset were performed. Model performance was reported with the concordance index (C-index) and the time-dependent area under the curve (AUC) (1-5 years). Results STA-Risk achieved C-indexes of 0.72 with the CSAW-CC data and 0.73 with the independent cohort data and outperformed all the compared risk models (0.67-0.70 and 0.66-0.72, respectively), with consistently higher AUCs in the 1-to 5-year risk predictions. Ablation studies revealed that all three key components of STA-Risk contributed to this improved performance. Domain shifts were observed, but their effects were mitigated with joint training strategy; the resulting model achieved cross-cohort test C-indexes of 0.75 with the CSAW-CC dataset and 0.67 with the independent dataset. Conclusion The STA-Risk deep learning risk model constructed from spatiotemporal asymmetries detected on longitudinal mammograms improves breast cancer risk prediction over existing models. ©RSNA, 2026.
Several studies have reported the potential effectiveness of indocyanine green fluorescence angiography (ICG-FA) for preventing anastomotic leakage (AL) in rectal cancer surgery; however, its clinical benefit remains uncertain. The purpose of this study was to investigate the effectiveness of ICG-FA in rectal cancer surgery in Japan using real-world data. We retrieved data from the Diagnosis Procedure Combination database in Japan for rectal cancer surgeries between April 2018 and March 2022. A total of 68,022 cases were registered, and 55,299 eligible patients were analyzed. Using a two-level structure of nested individuals from 1,057 hospitals, we applied multilevel logistic regression. A total of 40,013 laparoscopic (72.4%), 7,464 robotic (13.5%), and 7,822 open (14.1%) operations were performed. The rate of AL was 4.3% in the ICG-FA group and 5.1% in the non-ICG-FA group. After adjustment for patient- and hospital-level factors, ICG-FA was associated with a lower risk of AL (OR 0.87, 95% CI 0.76-1.00, p = 0.043); however, after additional adjustment for fiscal year, the association was no longer statistically significant (OR 0.91, 95% CI 0.79-1.04, p = 0.167). ICG-FA may be associated with a lower risk of AL after rectal cancer surgery in real-world settings, although the benefit was not statistically significant after additional adjustment for fiscal year.
Despite clinical advances, breast cancer screening adherence remains stagnant in Japan (<50%) compared with the United States (>70%). Understanding distinct cross-cultural barriers is essential; however, traditional methodologies often fail to capture visceral, real-world individual experiences and hidden deterrents to screening. This study aims to characterize and compare cross-cultural informatics profiles of barriers to breast cancer screening across Japanese-language and English-language social media discourse. We developed an automated natural language processing pipeline on a cloud-based informatics platform to analyze 46,823 screening-related posts (30,027 in Japanese and 16,796 in English) from X (formerly Twitter) collected in 2025, derived from an initial 76,955 posts after noise exclusion. The methodology integrated large language model-assisted sentiment polarity scoring with strict negation-handling, co-occurrence network topology analysis, and advanced distributional visualizations, including raincloud and ridgeline plots. Subgroup comparisons (prescreening vs postscreening and ultrasound with vs without mammography) were evaluated. Among the 46,823 screening-related posts, overall sentiment distributions showed no practically meaningful cross-cultural divergence (Cohen d=0.049); however, domain-specific analyses revealed sharp disparities in barrier prevalence. Within the English-language cohort containing 16,796 posts, discourse exhibited a concentrated, moderate negative sentiment regarding systemic barriers, featuring "Cost" as the primary barrier (n=1239, 7.4%), while "Pain" ranked considerably lower (n=842, 5.0%). In contrast, the Japanese-language cohort containing 30,027 posts was heavily bottlenecked by psychosomatic barriers, governed by a tightly interconnected network of "Pain," "Fear," and "Appointment." "Pain" emerged as the overwhelmingly dominant barrier (n=5788, 19.3%). In the English-language cohort, "Dense" breasts emerged as a prominent clinical topic due to elevated public awareness, distinct from the financial narrative. The Japanese subgroup analyses identified a temporal transition from anticipatory psychological anxiety ("Fear," 739/3805, 19.4%) and logistical concerns ("Appointment," 1556/3805, 40.9%) before screening to a strong persistence of the discomfort memory of "Pain" (1160/7419, 15.6%). Furthermore, sentiment scores for mammography were significantly more negative than those for ultrasound alone (P<.001, Cohen d=0.264), and pain-related descriptors for ultrasound spiked from 5.0% (106/2110, ultrasound alone) to 18.2% (733/4017) when performed concurrently with mammography. Despite comparable overall emotional equilibrium, a fundamental dichotomy emerged. The English-language discourse predominantly reflects US-specific systemic financial burdens, whereas the Japanese experience is characterized by emotional volatility transitioning from anticipatory anxiety to a tightly interconnected "Pain-Fear-Appointment" network. Physical discomfort of mammography dominates the screening narrative, overshadowing concurrent painless modalities like ultrasound. Improving adherence in Japan requires individualized pain-mitigating compression protocols and optimized clinical workflows to decouple mammographic discomfort from supplemental screening, thereby preventing pain-associated defensive avoidance and reducing logistical hurdles to improve equitable access.
We sought to compare real-world outcomes of robotic hysterectomy (RH) with laparoscopic (LH) and open (OH) hysterectomy among adults living with endometrial cancer in Alberta, Canada. We used administrative data to identify adults living with endometrial cancer who underwent a total hysterectomy (2012 to 2022) in Alberta. We applied generalized linear regression models and adjusted for confounders using propensity score overlap weighting. We presented predicted means and estimated probabilities with 95% confidence intervals (CIs). We included 4555 patients. In adjusted analyses, patients who underwent RH had a shorter length of hospital stay (1.2 [95% CI 1.2 to 1.3] d) than those who underwent LH (2.0 [95% CI 1.9 to 2.1] d) or OH (3.7 [95% CI 3.6 to 3.8] d). Duration of surgery for RH was shorter than LH (172 [95% CI 169 to 174] min v. 186 [95% CI 183 to 189] min), and longer than OH (173 [95% CI 171 to 175] min v. 169 [95% CI 167 to 171] min). Compared with patients who underwent OH, those who underwent RH had reduced probabilities of blood transfusions (2.2% [95% CI 1.3% to 3.9%] v. 6.6% [95% CI 4.8% to 9.0%]), perioperative complications (12.7% [95% CI 10.2% to 15.8%] v. 20.5% [95% CI 17.3% to 24.0%]), infections (16.5% [95% CI 13.6% to 19.8%] v. 33.8% [95% CI 30.0% to 37.9%]), and 30-day acute care readmissions (11.7% [95% CI 9.2% to 14.6%] v. 17.9% [95% CI 14.9% to 21.3]); no differences were observed in comparisons with LH. Among adults living with endometrial cancer in Alberta, RH was associated with a shorter length of hospital stay than LH and OH; we also noted fewer blood transfusions, complications, infections, and readmissions for RH compared with OH but not LH. Findings can be used in the context of surgical volumes and outcomes, along with other considerations, to guide decisions.
Purpose We aimed to describe the treatment landscape for biliary tract cancer (BTC), including patient characteristics, initial treatment patterns, and survival outcomes, and examine factors associated with receiving no active anticancer treatment (NT). Methods We conducted a retrospective cohort study of patients diagnosed with BTC between April 2014 and March 2020 identified through cancer registries and linked with the Kyoto City Integrated Database. Patient characteristics, factors associated with NT, and median overall survival (mOS) were analyzed using multivariate logistic regression and Kaplan-Meier methods. Results Among 1367 eligible patients, 30.1% underwent curative surgery, whereas 44.3% received NT. NT was significantly associated with distant metastasis (adjusted odds ratio [AOR] 4.24; 95% CI 2.92-6.15), certified long-term care (AOR 2.34; 1.76-3.10), and age ≥75 years (AOR 2.23; 1.70-2.93). The mOS was 54.6 months in the curative surgery group, 7.7-18.0 months in the noncurative surgical and nonsurgical treatment groups, and 5.2 months in the NT group. Conclusions Over 40% of patients with BTC in Kyoto City received no active treatment and had shorter survival. Older age and certification for long-term care were significantly associated with the selection of no active treatment. These findings describe treatment patterns among older adults with BTC and may help inform future strategies to improve treatment access, supportive care, and early detection.
The growing availability of public genomic repositories led to increased use of integrative and meta-analytic approaches to combine multi-omics datasets for biomarker discovery. Building on this framework, our study applies a molecular discovery approach to identify diagnostic biomarkers for cervical pre-cancer in high-risk HPV-positive women using aggregated genomic evidence across populations. This study performed a secondary analysis of publicly available DNA-methylation datasets identified through a systematic search of the Gene Expression Omnibus database to enable integrative analysis. After employing standard preprocessing methods across the selected DNA-methylation datasets, statistical analyses (specifically limma and meta-analysis with a random-effects model) were used to calculate the cumulative standardized effect sizes for all 9570 genes across the 4 selected studies. This cross-dataset analysis led to the identification of 4 promising, non-population-specific genes, that show potential for detecting precancerous cervical lesions in high-risk HPV-positive women. Collectively, these genes reflect a molecular profile associated with Cervical Intraepithelial Neoplasia lesions undergoing malignant progression. By leveraging aggregated data, our findings enhance the potential of generalization of biomarker signals and illustrate the strength of multi-data sets integration in advancing cervical pre-cancer triage screening strategies. Given their diagnostic promise, further experimental validation in large and diverse cohorts is warranted to evaluate their clinical applicability.
PANoptosis has emerged as a compelling strategy to potentiate antitumor immune responses. However, achieving specific PANoptotic cancer-cell death while sparing normal tissues remains a central challenge, as current strategies are constrained by inadequate spatiotemporal controllability and insufficient generation of key effector species, particularly reactive oxygen species (ROS). In this study, we report a class of PANoptosis nanoinducer constructed from atomically dispersed high-entropy metal sites, enabling spatiotemporally controlled near-infrared (NIR)-amplified cancer immunotherapy. The unique high-entropy metal-site configuration of the resulting nanozymes (HENA@PEG) boosts catalytic efficiency through atomic-level synergism, while enabling precise, pH-gated control over ROS generation via catalytic activation. In addition, nanozyme-mediated photothermal therapy (PTT) not only induces direct tumor ablation but also supplies exogenous thermal energy to accelerate the catalytic reactions. The co-programmed integration of endogenous and exogenous activations confers tumor-site-adaptive biocatalysis, thereby enabling precise spatiotemporal induction of PANoptosis. Both in vitro and in vivo investigations reveal that the resulting nanoinducer effectively promotes dendritic cell maturation and cytotoxic T-cell activation, ultimately amplifying antitumor immune responses and markedly suppressing 4T1 tumor progression. Overall, this work establishes a high-entropy-engineered nanoinducer that overcomes the limitations of nonspecific PANoptosis and immune evasion, representing a promising avenue toward more efficient and precisely targeted cancer immunotherapy.
Accurate and early detection of breast cancer in screening mammography remains a critical challenge in medical imaging, particularly due to variations in image quality, tissue density, and annotation standards across datasets. This study aims to design and validate a Hierarchical Transfer Learning (HTL) framework that leverages heterogeneous mammography datasets and multi‑stage pre-processing to achieve more accurate and generalizable deep learning-based detection of breast lesions in screening mammography. Our approach integrates five image enhancement techniques, CLAHE, Gamma Correction, Adaptive Histogram Equalization, Global Histogram Equalization, and Unsharp Masking into the learning process, allowing the model to adapt progressively to enhancement specific features. We evaluate the framework using two state-of-the-art object detection architectures, YOLOv8 and Faster R-CNN, across three publicly available datasets (INbreast, CBIS-DDSM, and MIAS) and a locally collected dataset. Our HTL model achieves a peak mean Average Precision (mAP) of 0.981 and accuracy of 0.998, outperforming previous methods in both generalizability and precision. Moreover, the model maintains robust performance on real-world local data, demonstrating its practical utility for deployment in diverse clinical environments. These results confirm that hierarchical learning combined with strategic image enhancement and pre-processing significantly improves detection performance and supports large scale breast cancer screening applications with robust cross-dataset generalization, enabling consistent performance across heterogeneous imaging domains with varying acquisition protocols, image quality, and annotation standards.
Predicting survival in lung cancer patients, particularly those with brain metastases, is crucial for personalizing treatment plans and estimating patient prognosis. This minireview synthesizes findings from fifteen recent studies published between 2020 and 2026, focusing on survival prediction in lung cancer patients with brain metastases, with key outcomes including overall survival, progression-free survival, and intracranial progressionfree survival. Traditional and current approaches for predicting survival are discussed, along with comparisons between unimodal and multimodal approaches. Moreover, the strengths and limitations of existing methods are critically analyzed. The findings emphasize the potential of advanced predictive modeling to inform personalized treatment plans and improve survival outcomes in this high-risk population.
Chimeric antigen receptor (CAR) T-cell therapy has substantially improved outcomes in refractory hematologic malignancies but may cause cardiovascular complications, particularly in the context of cytokine release syndrome (CRS). Real-world data on incidence, severity, and prognostic relevance of cancer therapy-related cardiovascular toxicity (CTR-CVT) defined by the 2022 ESC cardio-oncology guidelines remain in the context of CAR-T cell therapy limited. This retrospective single-center study includes 104 patients treated with CAR T-cells between 09/2019 and 02/2024 for acute lymphoblastic leukemia, non-Hodgkin lymphoma and multiple myeloma. The primary endpoint was new-onset CTR-CVT during hospital stay, defined as cancer therapy-related cardiac dysfunction (CTRCD), arrhythmia, myocardial infarction, cardiogenic shock, or cardiovascular death. Clinical characteristics, biomarkers, echocardiographic parameters, CRS/ICANS severity, and survival outcomes were analyzed. Fifty-two patients (50%) met criteria for CTR-CVT, predominantly due to asymptomatic biomarker elevation. CTRCD occurred in 48.1%, whereas clinically significant events were rare: three patients developed symptomatic CTRCD, one experienced cardiogenic shock, and no myocardial infarctions or cardiovascular deaths were observed. Cardiovascular events occurred early and were associated with higher-grade CRS and ICANS, as well as elevated inflammatory markers. Reduced baseline left ventricular ejection fraction, elevated systolic pulmonary artery pressure, impaired performance status, and beta-blocker use were associated with increased CTR-CVT risk. Survival was numerically lower in patients with CTR-CVT but did not reach statistical significance. Although half of patients fulfilled ESC criteria for CTR-CVT, clinically relevant cardiac events after CAR T-cell therapy were uncommon. These findings suggest potential overclassification driven by biomarker elevations and underscore the importance of emphasizing clinical relevance when assessing cardiotoxicity in CAR T-cell recipients.
Cervical cancer (CC) remains one of the most common malignancies worldwide, particularly in low-resource countries. Expression of programmed death-ligand 1 (PD-L1) has emerged as an immune-related biomarker with predictive and potential prognostic relevance in several cancer types. However, its prognostic role in CC remains unclear. This study investigated the clinicopathological and prognostic significance of tumoral PD-L1 expression in CC. This monocentric retrospective study included 113 patients diagnosed with invasive CC at the University Hospital Bonn between 2002 and 2016. Clinical and histopathological data were obtained from patient records, and immunohistochemical analyses were performed on tissue microarrays for PD-L1 [evaluated by Tumor Proportion Score (TPS) and Combined Positive Score (CPS)], p16, p53, Ki-67, and estrogen and progesterone receptors. PD-L1 expression was positive by TPS in 15.9% and CPS by 54.9% of cases. No significant association was found between PD-L1 expression and most clinicopathological parameters. In univariate analysis, increasing age was associated with worse overall survival (OS) and showed a trend towards reduced progression-free survival (PFS). Advanced International Federation of Gynecology and Obstetrics (FIGO) stage was associated with reduced PFS and OS. The presence of distant metastases was associated with worse OS but had no impact on PFS. Primary surgical treatment was associated with improved PFS and OS. Progesterone receptor positivity correlated with improved PFS. In multivariate analysis, PD-L1 positivity by CPS was independently associated with improved OS, whereas PD-L1 positivity by TPS was not. FIGO stage remained the dominant prognostic factor for OS. Tumoral PD-L1 expression, assessed by CPS, is an independent favorable prognostic factor for OS in CC, whereas TPS-based assessment lacked prognostic impact. CPS scoring may therefore provide superior biological and prognostic insight into PD-L1-related immune activity in CC.