Cancer Research Articles

Mechanosensitive nuclear uptake of chemotherapy.

The nucleus is at the nexus of mechanotransduction and the final barrier for most first line chemotherapeutics. Here, we study the intersection between nuclear-cytoskeletal coupling and chemotherapy nuclear internalization. We find that chronic and acute modulation of intracellular filaments changes nuclear influx of doxorubicin (DOX). Rapid changes in cell strain by disruption of cytoskeletal and nuclear filaments sensitize nuclei to DOX, whereas chronic reduction of cell strain desensitize nuclei to DOX. Extracted nuclei from invasive cancer cells lines from different tissues have distinct nuclear permeability to DOX. Last, we show that mechano-priming of cells by paclitaxel markedly improves DOX nuclear internalization, rationalizing the observed drug synergies. Our findings reveal that nuclear uptake is a critical, previously unquantified aspect of drug resistance. With nuclear permeability to chemotherapy being tunable via modulation of nuclear mechanotransduction, mechano-priming may be useful to help overcome drug resistance in the future.

Exploring Gender Differences in Receipt of the 5As for Smoking Cessation for Recently-Diagnosed Cancer Patients (ECOG-ACRIN EAQ171CD).

Smoking cessation is important for men and women diagnosed with cancer. Oncology clinicians should encourage all patients to quit and offer resources to help them do so, following the 5As framework (Ask, Advise, Assess, Assist, and Arrange follow-up). This study tests gender differences in self-reported receipt of the 5As by an oncology provider among 306 recently-diagnosed male and female cancer patients. Receipt of praise for quitting efforts was also assessed as an indicator of empathic communication. Participants completed baseline surveys as part of a larger clinical trial focused on smoking cessation (NCT03808818), reflecting on pre-trial interactions with their oncology clinicians. Most male and female patients received "Ask," "Advise," and "Assess" (i.e., asking patients if they smoke, advising them to quit, and assessing their interest in doing so), though significant gender differences emerged in receiving "Assist" and "Arrange follow-up." Women were less likely to receive assistance (e.g., medication or counseling referral; 85.25% versus 93.18%, respectively) or a follow-up appointment to discuss their progress (28.11% versus 40.91%, respectively). Approximately half of men and women were praised for their quitting efforts. In exploratory sensitivity analyses, gender differences in arrange-follow-up were attenuated when adjusting for cancer location (smoking-related or not), self-reported distress, and self-reported coping ability. Women may be at risk for suboptimal smoking-related support during cancer care, as assistance and follow-up are essential to sustained abstinence. Clinicians should consistently deliver each of the 5As to all cancer patients who smoke, regardless of cancer type or expressed distress/coping difficulty. The current study findings add to the growing literature describing gender disparities in tobacco treatment access. Findings highlight an addressable gap in access to tobacco treatment for a group of women who have cancer. Advancements in the equitable delivery of smoking cessation counseling have the potential to improve cessation outcomes for women with cancer who smoke.

Collagen Density Is Associated With Pathological Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients.

The tumor-associated stroma is an essential compartment in breast cancer, and collagen fiber organization in the stroma has been reported to be correlated with prognosis. In this study, we sought to evaluate collagen fiber characteristics in relation to pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 388 breast cancer patients receiving NAC were enrolled. The stroma type was manually assessed on pretreatment hematoxylin and eosin (HE)-stained slides, and the collagen fiber features were quantified by a computer tool. The relationship between syndecan-1 expression and collagen fibers and its correlation with treatment efficacy were detected by immunohistochemistry. The pCR rate of patients with collagen-dominant stroma was lower than that of patients with lymphocyte-dominant stroma (19.6% vs. 40.0%, p = 0.001). Patients who achieved pCR had straighter and less dense fibers in pretreatment biopsied tissue than non-pCR patients (p = 0.031, p = 0.044). Additionally, the pCR group had greater syndecans-1 expression on the tumor epithelium than the non-pCR group (p < 0.001), while there was no statistically significant difference in the stroma (p = 0.333). Collagen fiber density was the only factor associated with pCR after correction for other clinicopathological variables in triple-negative breast cancer (TNBC)patients (OR 0.466, 95% CI 0.227-0.956, p = 0.037); patients with lower fiber density had a greater pCR rate (37.5% vs. 12.5%, p = 0.021). Collagen fiber density was associated with pCR in patients with breast cancer, and it could be a potential candidate for discriminating between responders and nonresponders for TNBC patients receiving NAC.

Cardiovascular mortality trends and disparities in U.S. breast cancer patients, 1999–2020: a population-based retrospective study

BackgroundBreast cancer survivors face a higher risk of cardiovascular disease (CVD) compared to non-breast cancer patients, yet contemporary data on CVD-related mortality within this group remains scarce.ObjectiveTo investigate trends and disparities in CVD mortality among breast cancer patients.MethodsWe queried the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research (CDC Wonder) and conducted serial cross-sectional analyses on national death certificate data for CVD mortality in breast cancer patients aged 25 and above from 1999 to 2020. We calculated age-adjusted mortality rates (AAMR) per 100,000 individuals and analyzed trends over time using the Joinpoint Regression Program, with further analyses stratified by age, race, census region, and urbanization level.ResultsA total of 74,733 CVDs with comorbid breast cancer in the United States were identified between 1999 and 2020. The AAMR from CVDs with comorbid breast cancer decreased from 2.57 (95% CI [2.50–2.65]) in 1999 to 1.20 (95% CI [1.15–1.24]) in 2020, with an average annual percent change (AAPC) of − 4.3. The three most common causes of CVDs were ischemic heart disease (47.8%), cerebrovascular disease (17.1%), and hypertensive disease (10.6%). Our analysis revealed a significant decrease in AAMR for all CVD subtypes, except for hypertensive diseases and arrhythmias. The decrease in annual percent change (APC) was more pronounced in individuals aged ≥ 65 years compared to those < 65 years (-4.4, 95%CI [-4.9, -3.9] vs. -2.9, 95%CI [-4.1, -1.7], respectively. Notably, non-Hispanic Blacks consistently exhibited the highest AAMR (1.95, 95%CI [1.90–1.99]), whereas Hispanic or Latina patients had the lowest AAMR (0.75, 95% CI [0.72–0.78]). The AAMR was also higher in rural regions than in urban areas (1.64, 95%CI [1.62–1.67] vs. 1.55, 95%CI [1.53–1.56]).ConclusionThe study highlights a significant decline in CVD mortality among breast cancer patients over two decades, with persistent disparities by race and region. Exceptionally, hypertensive diseases and arrhythmias did not follow this declining trend.

The effect of maternal dietary polyphenol consumption on offspring metabolism.

The early intrauterine environment of mothers during pregnancy significantly affects the metabolic health of their offspring. Existing studies suggest that poor maternal nutrition during pregnancy increases the risk of obesity or diabetes in offspring, so it is highly important to intervene during pregnancy to prevent metabolic disorders in mothers and their offspring. Polyphenols with anti-inflammatory and antioxidant properties are found in many foods and have protective effects on obesity, diabetes, cancer, and cardiovascular disease. Furthermore, recent evidence indicates that maternal dietary polyphenols could be a potential therapy for improving pregnancy outcomes and offspring metabolism. In this review, we discuss the studies and mechanisms of different kinds of maternal dietary polyphenols during pregnancy and lactation in improving the metabolism of offspring, analyze the limitations of the current studies, and propose possible directions of further research, which provide new ideas and directions for reducing metabolic diseases in offspring.

The Effect of Reflexology Socks in the Management of Opioid-Induced Constipation: A Randomized Controlled Trial.

Constipation is an important symptom that is common in patients using opioids and leads to major health problems among patients. Reflexology is one of the approaches utilized to manage constipation. To examine the effect of reflexology socks on constipation in patients with opioid-induced constipation. This study was designed as a single-blind, randomized, controlled experimental trial. The study was conducted with the participation of a total of 101 patients who were suffering from cancer and other noncancer diseases, using opioids, and complaining of constipation. The patients in the intervention group (n = 51) were advised to walk with reflexology socks for 4 weeks, whereas the patients in the control group (n = 50) were advised to walk only. It was found that the severity of opioid-induced constipation was lower in the intervention group than in the control group at the end of the fifth week (P < .05). Additionally, after the application, the quality-of-life mean score was lower in the intervention group (mean, 48.46 ± 24.66) compared with control group (mean, 109.88 ± 10.62), and reflexology socks were effective in enhancing quality of life in the intervention group (P < .05). This study concluded that reflexology socks were an effective approach to the management of constipation. Reflexology socks may be more useful for patients to manage constipation because it is difficult to find a reflexologist, and reflexology sessions are charged and expensive. In this way, patients will wear reflexology socks comfortably and easily at home, and the severity of constipation will be alleviated.

A comprehensive analysis of household air pollution due to traditional cooking in the himalayan belt

Abstract Household air pollution (HAP) and its health concerns are a significant challenge in the Indian subcontinent and other developing nations. Approximately 4.3 million deaths worldwide are attributed to indoor air pollution rather than outdoor air pollution, most of which occur in low- and middle-income countries. Traditional cookstoves, widely used in rural Himalayan areas of India, Nepal, and Pakistan, emit pollutants like particulate matter (PM), carbon monoxide (CO), and carbon dioxide (CO2). These stoves, which burn solid fuels such as wood, dung, charcoal, and agricultural waste, contribute to respiratory infections, cancer, premature mortality, and cardiovascular diseases. Improving biomass cookstoves can help reduce exposure to the harmful indoor air pollutants. This study evaluates household pollution levels in Uttarakhand, India, using direct data collection to determine the daily contaminant exposure. The findings show extremely high PM 2.5 and 10 emissions (2,100 μg/m³ and 5,000 μg/m³, respectively) due to inefficient cookstove design and incomplete fuel combustion. By comparing traditional and improved cookstoves using standardized testing protocols, the study also measures the efficiency and identifies the causes of high emissions. The results corroborated the hypothesis that traditional cookstoves have a very low thermal efficiency of ∼11 %, leading to the high emissions gathered from sensor data. This comparison provides specific insights into the reasons behind high emissions and suggests targeted improvements. The findings suggest potential improvements in cookstove efficiency, offering a foundation for further research and stakeholder involvement to enhance rural livelihoods in India.

End Binding Proteins: Drivers of Cancer Progression.

Cancer, a complex and heterogeneous disease, continues to be a major global health concern. Despite advancements in diagnostics and therapeutics, the aggressive nature of certain cancers remain a significant challenge, necessitating a deeper understanding of the underlying molecular mechanisms driving their severity and progression. Cancer severity and progression depend on cellular properties such as cell migration, cell division, cell shape changes, and intracellular transport, all of which are driven by dynamic cellular microtubules. Dynamic properties of microtubules, in turn, are regulated by an array of proteins that influence their stability and growth. Among these regulators, End Binding (EB) proteins stand out as critical orchestrators of microtubule dynamics at their growing plus ends. Beyond their fundamental role in normal cellular functions, recent research has uncovered compelling evidence linking EB proteins to the pathogenesis of various diseases, including cancer progression. As the field of cancer research advances, the clinical implication of EB proteins role in cancer severity and aggressiveness become increasingly evident. This review aims to comprehensively explore the role of microtubule-associated EB proteins in influencing the severity and aggressiveness of cancer. We also discuss the potential significance of EB as a clinical biomarker for cancer diagnosis and prognosis and as a target for therapeutic intervention.

Factors associated with post acute care utilization after mastectomy for breast cancer patients.

Although the demand for care immediately after mastectomy is rising, and such medical services are referred to as post-acute care (PAC), there is limited evidence on the factors influencing PAC choices among these patients in Korea. A total of 106,670 patients diagnosed with breast cancer and undergoing mastectomy were extracted from the Central Cancer Registry data from 2012 to 2019 using Public Cancer Library data of KCURE. PAC was defined as utilization of long-term care hospital (LTCH), hospital-based nursing care (HBNC), or HBC (hospital-based care) within 2 months post-surgery. Multinomial logistic regression was used to identify factors associated with different types of PAC utilization. The utilization patterns of different types of PAC within 2 months after mastectomy were associated with age, income, cancer severity, and particularly the region of residence (Metropolitan; HBNC, OR 0.16, 95% CI 0.10-0.26; LTCH, OR 2.35, 95% CI 2.21-2.50; HBC, OR 2.17, 95% CI 1.97-2.39), as well as the location (capital areas; HBNC, OR 12.46, 95% CI 4.97-31.25; LTCH, OR 1.21, 95% CI 1.15-1.28; HBC, OR 1.90, 95% CI 1.74-2.07) and type of the hospital (tertiary hospital; HBNC, OR 13.70, 95% CI 7.86-23.86; LTCH, OR 1.45, 95% CI 1.37-1.53; HBC, OR 3.38, 95% CI 3.00-3.80) where the surgery was performed. In this study, we found the factors associated with PAC utilization on mastectomy patients. Our study found that middle-aged breast cancer patients, residents of metropolitan or rural areas, and those who underwent surgery at hospitals in capital area were particularly associated with higher utilization of inpatient-related PAC services. Breast cancer patients with higher income, older adults, metropolitan residents, patients who underwent breast cancer surgery at metropolitan hospitals, and those treated at tertiary hospitals were strongly associated with higher utilization of HBNC services. Identifying factors that determine the use of PAC has meaningful implications for patients and healthcare systems.

Personalized deep learning auto-segmentation models for adaptive fractionated magnetic resonance-guided radiation therapy of the abdomen.

Manual contour corrections during fractionated magnetic resonance (MR)-guided radiotherapy (MRgRT) are time-consuming. Conventional population models for deep learning auto-segmentation might be suboptimal for MRgRT at MR-Linacs since they do not incorporate manual segmentation from treatment planning and previous fractions. In this work, we investigate patient-specific (PS) auto-segmentation methods leveraging expert-segmented planning and prior fraction MR images (MRIs) to improve auto-segmentation on consecutive treatmentdays. Data from 151 abdominal cancer patients treated at a 0.35T MR-Linac (151 planning and 215 fraction MRIs) were included. Population baseline models (BMs) were trained on 107 planning MRIs for one-class segmentation of the aorta, bowel, duodenum, kidneys, liver, spinal canal, and stomach. PS models were obtained by fine-tuning the BMs using the planning MRI ( ). Maximal improvement by continuously updating the PS models was investigated by adding the first four out of five fraction MRIs ( ). Similarly, PS models without BM were trained ( and ). All hyperparameters were optimized using 23 patients, and the methods were tested on the remaining 21 patients. Evaluation involved Dice similarity coefficient (DSC), average ( ) and the 95th percentile (HD95) Hausdorff distance. A qualitative contour assessment by a radiation oncologist was performed for BM, , and . and networks had the best geometric performance. and BMs showed similar DSC and HDs values, however models outperformed BMs. predictions scored the best in the qualitative evaluation, followed by the BMs and models. Personalized auto-segmentation models outperformed the population BMs. In most cases, delineations were judged to be directly usable for treatment adaptation without further corrections, suggesting a potential time saving during fractionatedtreatment.

Reconstruction of the pelvic floor and perineal wound after extralevator abdominoperineal resection of the rectum.

This article presents an innovative technique for perineal wound reconstruction following extralevator abdominoperineal excision (ELAPE) in rectal cancer surgery. The authors trace the evolution of surgical methods for rectal cancer treatment, from W.E. Miles' abdominoperineal resection (APR) to T. Holm's ELAPE technique introduced in 2007. The proposed metod's primary advantage lies in its ability to completely fill the extensive deep and superficial perineal wound defect by moving two flaps from both sides of the wound and overlapping them. This approach potentially reduces postoperative complications and improves patients' quality of life following ELAPE. The authors describe the procedure in detail, including specific measurements and angles for flap creation. They also present a case study of a 52-year-old female patient with lower rectal ampulla cancer, demonstrating the practical application of this technique. This innovative reconstruction method addresses the current lack of consensus on perineal wound plastic surgery techniques following ELAPE and offers a promising solution to reduce postoperative morbidity in rectal cancer patients undergoing this procedure.

Effects of intravenous anesthesia and inhalation anesthesia on postoperative inflammatory markers in patients with esophageal cancer: a retrospective study

BackgroundInflammatory markers have been confirmed to be associated with the prognosis of cancer patients. In this study, we compared the impacts of intravenous anesthesia and inhalation anesthesia on the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) after esophageal cancer surgery.MethodsWe retrospectively reviewed the electronic medical records of patients who underwent esophagectomy from January 1, 2014 to December 31, 2016. Patients respectively received total intravenous anesthesia (TIVA) or inhalational anesthesia (INHA). Inverse probability of treatment weighting (IPTW) was employed to minimize differences. The Mann-Whitney U test or Kruskal Wallis test was utilized to compare the effect of the two groups on postoperative NLR, PLR and SII.ResultsA total of 519 patients who had undergone esophageal cancer resection were recruited in this study, among whom 339 patients were eligible (TIVA group, n = 201, INHA group, n = 138). After IPTW, there was no statistically significant difference in NLR, PLR, and SII on the first postoperative day(P = 0.1951), (P = 0.5611), (P = 0.9684) and on the third postoperative day(P = 0.5961), (P = 0.1804), (P = 0.9653) between the two groups.ConclusionsIn conclusion, there was no significant difference in NLR, PLR and SII between intravenous anesthesia or inhalational anesthesia. TIVA is not superior to INHA in reducing the perioperative inflammatory response of esophageal cancer.SynopsisInflammatory markers play an important role in the recurrence, metastasis and survival of tumor patients after surgery. In this study, we will compare the effects of different anesthesia methods on inflammatory markers.

Cardiovascular adverse events in patients with HER2-positive breast cancer treated with trastuzumab-drug conjugates : a Bayesian disproportional real world study for signal detection leveraging the FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background The cardiovascular risk profiles of trastuzumab drug conjugates (T-DCs) in the treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer are uncertain. This study analyzed real-world adverse events data from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to investigate the association between T-DCs and major adverse cardiovascular events (MACE). Methods We searched the FAERS database for reports of cardiovascular adverse events in patients with HER2-positive breast cancer receiving trastuzumab, ado-trastuzumab emtansine (T-DM1), and trastuzumab deruxtecan (T-Dxd). The primary endpoint was MACE and the secondary endpoint was other cardiovascular events. Results Between January 2015 and April 2024, out of the 135,226 drug-adverse event pairs analyzed, 8,497 were cardiovascular events, with 4,457 classified as MACE and 4,040 as other cardiovascular events. Trastuzumab reached pharmacovigilance for MACE (ROR = 1.39, 95%CI: 1.30–1.49, IC025 = 0.25), while neither T-DM1 (ROR = 0.78, 95%CI: 0.69–0.88, IC025=-0.51) nor T-Dxd (ROR = 0.63, 95%CI: 0.52–0.76, IC025=-0.93) reached MACE-related pharmacovigilance. Among MACE, stroke linked to T-DM1 (ROR = 1.86, 95%CI: 1.42–2.43, IC025 = 0.35) and T-Dxd (ROR = 2.44, 95%CI: 1.68–3.56, IC025 = 0.57) both reached pharmacovigilance in younger patients (<65 years). Proportionate analysis showed age and weight were the two key factors contributing to the occurrence of T-DCs induced MACE. Conclusion HER2-positive breast cancer patients receiving T-DCs require additional cardiac monitoring, particularly for stroke in younger patients.

Construction of a novel copper-induced-cell-death-related gene signature for prognosis in colon cancer, with focus on KIF7

BackgroundColon cancer (CC) is a leading cause of cancer-related mortality worldwide. Accurate prognostic markers are essential for patient risk stratification and personalized treatment. Copper-induced cell-death-related genes (CRG) have emerged as potential players in cancer prognosis, yet their role in CC remains unclear.MethodsThis study aimed to comprehensively evaluate the expression of CRG and their roles in CC using gene expression and clinical data from TCGA and GEO databases. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses identified prognostic genes, leading to the construction of a CRG prognostic signature. The signature’s predictive accuracy was validated using Kaplan-Meier survival curves, Receiver Operating Characteristic (ROC) curves, and a nomogram model. Additionally, we conducted experiments including immunofluorescence staining and cellular assays to validate the key genes’ biological functions.ResultsA 12-gene CRG signature was significantly associated with overall survival in CC patients. The high-risk group, as classified by median risk score, exhibited significantly shorter survival times compared to the low-risk group. The signature’s predictive accuracy was further confirmed with Area Under the Curve (AUC) scores exceeding 0.75 in TCGA and GSE17536 cohorts. Notably, the risk score was significantly correlated with immune checkpoints, chemotherapy sensitivity, and tumor microenvironment. Furthermore, the risk score showed a strong association with immunotherapy response in patients from GSE78220 and GSE39688 cohorts. Bioinformatics analysis of KIF7, a key gene within the signature, revealed its upregulation in CC and significant associations with tumor mutation burden, microsatellite instability, and immune cell infiltration across various cancers. Experiments confirmed that KIF7 was upregulated in CC and its knockdown reduced cell proliferation, migration, and invasion.ConclusionThe CRG prognostic signature can effectively predict overall survival, immune microenvironment and chemotherapy response in CC. KIF7, as a potential prognostic marker, has significant potential for the prediction and treatment of CC.

Association between EASIX and acute kidney injury in critically ill cancer patients

BackgroundTo analyze the relationship between endothelial activation and stress index (EASIX) and the occurrence of acute kidney injury (AKI) in critically ill cancer patients. MethodsCritically ill cancer patients were selected from the Medical Information Mart for Intensive Care IV (MIMIC-IV). Multivariate logistic regression was used to analyze the association between EASIX and the occurrence of AKI in critically ill cancer patients.ResultsOne thousand forty-one cancer patients were retrospectively included, including 607 men and 434 women with mean age of 64.86 ± 13.67 years. Univariate analysis showed that high EASIX levels were associated with an increased risk of AKI occurrence in intensive care unit (ICU) cancer patients (OR: 1.47,95% CI: 1.13–1.91, P < 0.05). After adjusting for other confounders, high EASIX levels remained an independent risk factor predicting the development of AKI (OR: 1.42,95% CI: 1.08–1.88, P < 0.05). Trends in effect sizes were generally consistent across all subgroups in the prespecified subgroup analyses.ConclusionEASIX is an independent risk factor for AKI in critically ill cancer patients. More prospective studies are needed to validate the effect of EASIX on the occurrence of AKI in critically ill cancer patients in the future.

Validation of the European Oncology toolkit for the self-assessment of Quality of Life (EUonQoL-Kit) in cancer patients and survivors: study protocol of a pan European survey

BackgroundEuropean cancer programmes and policies lack a unified health-related quality of life (HRQoL) assessment tool. The European oncology quality of life toolkit (EUonQoL-Kit) is a novel set of HRQoL questionnaires, co-designed with cancer patients and survivors, translated and culturally adapted into 31 European languages, and with both static and dynamic electronic administration modes. The main aim of this study is the psychometric assessment of the static version. Secondary aims include evaluating the EUonQoL-Kit acceptability, cross-validating the administration modes, exploring individual factors potentially affecting HRQoL and HRQoL inequalities between countries.MethodsA sample of 4,500 participants, including three groups (active treatment, survivors, and palliative care) from 45 centres in 25 EU Member States and 7 associated countries, will be enrolled in a multicentre observational cross-sectional study. All participants will complete the static EUonQoL-Kit; three subsamples (each 10% of the total sample) will also respectively complete the following: a) dynamic EUonQoL-Kit, based on Item Response Theory (IRT)/Computer Adaptive Testing (CAT), b) FACT-G and EQ-5L-5D, and c) static EUonQoL-Kit (re-test). Psychometric analyses will encompass exploratory and confirmatory factor analyses (measurement model and structural validity), Cronbach's alpha (internal consistency), intraclass correlation coefficient (test–retest reliability), Pearson/Spearman correlation (concurrent validity), comparison of group scores (construct validity), and Differential Item Functioning (cross-country item equivalence). Secondary analyses will evaluate participant response time and rate, and static/dynamic score differences. Regression models will estimate associations between individual factors and HRQoL.DiscussionThe EUonQoL-Kit will serve to systematically incorporate patient perspectives into European cancer policies and to address HRQoL inequalities across Europe.Trial registrationClinicalTrials.gov Identifier: NCT05947903, 2023–06-28.

Lack of an association between spleen volume and risk of pneumococcal infection in cancer patients: a nested case-control study

BackgroundThe spleen is a key organ in preventing pneumococcal infection, especially in patients with immunocompromised condition such as those with cancer. Previous studies have shown that a small spleen volume in pneumococcal pneumonia patients is associated with severe disease course. However, it is unknown whether a small spleen increases risk of pneumococcal infection. We investigated the association between spleen volume and risk of pneumococcal infection.MethodsThis study was a retrospective cohort study using a nested case-control design and involved adult patients with malignancy who underwent chest and/or abdominal CT scans from January 1, 2008, to September 30, 2020, at a tertiary care center in Japan. Exclusion criteria comprised patients diagnosed with hepatic cirrhosis, leukemia, lymphoma, and/or post-splenectomy. From the cohort group that met all selection criteria (n = 22475), we identified all incident cases of pneumococcal infection (pneumococcal pneumonia and/or invasive pneumococcal diseases) and matched them with four controls by age, sex, and follow-up duration. Odds ratios (ORs) for the association between spleen volume and pneumococcal infection were estimated using conditional logistic regression models adjusted for body surface area, performance status, Charlson comorbidity index, and metastatic cancer.ResultsThe median spleen volume was 85.8 (interquartile range, 65.8–120.8) cm3. Over a median follow-up of 4.95 (interquartile range, 1.54–9.25) years, 60 patients were diagnosed with pneumococcal infection (20 with invasive pneumococcal disease and 40 with pneumonia without invasive pneumococcal disease) and matched with 240 controls. Spleen volume reduction (per 10 cm3) did not increase risk of pneumococcal infection in a crude analysis [OR 1.04 (95% CI 0.98–1.11)]. The outcome remained unchanged in the multivariable analysis (OR 1.01 [95% CI 0.95–1.08]).ConclusionsSmall spleen volume did not increase risk of pneumococcal infection in cancer patients.

Changes in essential cancer medicines and association with cancer outcomes: an observational study of 158 countries

BackgroundCancer is a major cause of mortality worldwide, and differences in cancer mortality rates between countries are, in part, due to differences in access to cancer care, including medicines. National essential medicines lists (NEMLs) play a role in prioritization of healthcare expenditure and access to medicines. We examined the association between amenable cancer mortality and listing medicines used in the management of eight cancers (non-melanoma skin, uterine, breast, Hodgkin lymphoma, colon, leukemia, cervical, and testicular) in national essential medicines lists of 158 countries and summarized changes to the inclusion of cancer treatments in NEMLs.MethodsWe conducted a cross-sectional examination of NEMLs for 158 countries, which were obtained in May 2023. We identified medicines used to treat each of the eight cancers and determined the number of medicines listed by NEMLs for each cancer. We conducted multiple linear regressions to examine the association between the number of medicines listed on the NEMLs and cancer mortality.ResultsWe found associations between cancer medicine listing and outcomes for six of the eight examined cancers (non-melanoma skin cancer (p = 0.001), uterine cancer (p = 0.006), breast cancer (p = 0.001), Hodgkin lymphoma (p = 0.021), colon cancer (p = 0.006), and leukemia (p = 0.002)), when adjusting for healthcare expenditure and population size.ConclusionThere was an association between listing cancer medicines on NEMLs and cancer mortality. Further research is required to explore how cancer mortality may be impacted by other cancer interventions, as well as policies to improve equitable access to cancer care.

HPV genotypes in invasive cervical cancer: prevalence, risk attribution, and optimized vaccine strategies in western China

BackgroundUnderstanding the HPV genotype distribution in invasive cervical cancer (ICC) is essential for vaccine optimization. This study presents a comprehensive analysis of HPV genotypes in ICC tissues from patients in western China, with the aim of informing regional vaccine policy and prevention strategies.MethodsDNA was extracted from 1,908 paraffin-embedded ICC samples, and 23 HPV genotypes were detected via PCR and reverse dot hybridization gene chip assays. The genotypic distribution of HPV infections was analyzed, the attribution of each HPV genotype found in multiple infection cases was calculated using the fractional contribution approximation. Furthermore, the cumulative attribution rates of HPV genotypes included in each vaccine combination were totaled to estimate the potential vaccination coverage of ICC across various histologic types and age groups.ResultsThe overall prevalence of HPV infection was 94.9% (95% CI 93.8–95.8) among 1,908 women with ICC. HPV genotypes 16 and 18 were detected in 1645 of 1810 HPV-positive patients (90.9, 95% CI 89.5–92.1) of ICC. HPV16, 18, 33, 52, and 58 were detected in 1,749 patients (96.6, 95% CI 95.7–97.4), the five most common genotypes in different age groups. HPV genotypes contained in the 9-valent vaccine were detected in 1776 patients (98.1, 95% CI 97.4–98.7). By weighted imputation analysis, the cumulative attribution rates of the bivalent vaccine was 83.4%, and that of the nine-valent vaccine was 89.8%. Optimization group A included the five genotypes with the highest prevalence, HPV16, 18, 33, 52, and 58, with a cumulative attribution rates of 88.5%, and optimization group B included the nine most common HPV genotypes, HPV16, 18, 31, 33, 35, 45, 52, 58, and 59, with a cumulative attribution rates of 90.5%.ConclusionOur comprehensive postsurgical analysis of HPV in ICC patients in western China revealed that the incorporation of the bivalent vaccine into the national program is cost-effective, with group A optimization closely matching the vaccination coverage of the 9-valent vaccine, which can be used to guide future prevention strategies.

Gasdermin D (GSDM D) as a Potential Diagnostic Biomarker in Bladder Cancer: New Perspectives in Detection

Background: Traditional methods of bladder cancer (BC) diagnosis include clinical examination, imaging, urine tests, cystoscopy, and biopsy. Due to the complexity of detection, diagnostic markers of bladder cancer measured in blood are still being sought. The pathogenesis of BC is complex and depends on many factors. However, the available literature data suggest that gasdermin D (GSDM D) has an influence in the pathogenesis of cancers. This study is the first that assesses the significance and diagnostic utility of serum GSDM D in bladder cancer. Methods: A total of 80 serum samples were obtained and analysed from healthy volunteers (C) and bladder cancer patients. The cancer patients were further classified into two groups, low-grade (LG) and high-grade (HG) bladder cancer, according to the TNM classification. The serum levels of GSDM D, CEA, and CA19-9 were assessed following the manufacturer’s instructions using immunoassay techniques. Results: The concentrations of GSDM D were nearly twice as high in the serum of BC patients compared to controls. Additionally, the median of GSDM D concentration was notably elevated in LG and HG bladder cancer than in C. In the total study group, the GSDM D concentration correlated with CRP and CEA levels. The diagnostic sensitivity of GSDM D was higher than that of CEA, but slightly lower in comparison to CA19-9. Moreover, the negative predictive value of GSDM D was the highest among all tested markers. The highest positive predictive value and diagnostic accuracy were observed for CEA, while the accuracy of GSDM D was comparable. GSDM D had an AUC value of 0.741, which was similar to the AUC value of CEA. Conclusions: GSDM D in serum appears to be a valuable diagnostic biomarker, especially when its measurement is used in conjunction with other markers such as CEA. Its high sensitivity makes it effective for the early detection of bladder cancer.