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Clinical manifestations, genetic characteristics and laboratory markers of patients with epidermolysis bullosa: a single tertiary referral center experience.1 week agoEpidermolysis bullosa (EB) is a group of genetically and clinically heterogeneous diseases that presents as blisters, erosions, crusts, and scars.
In this retrospective study, we report the clinical manifestations, genetic characteristics, and laboratory markers of patients with EB.
Fifteen patients with EB were included in the study. The most common type was dystrophic EB (DEB) (n = 10), followed by EB simplex (EBS) (n = 3), junctional EB (JEB) (n = 1), and Kindler EB (n = 1). The disease onset was from birth in 13 patients. The most common cutaneous manifestations were erosions (n = 12), vesicles and bullae (n = 8), scars (n = 6), and milia (n = 6). Nail abnormalities were observed in 11 patients and mucosal involvement in seven patients. The most common genetic mutation was COL7A1 gene mutation (n = 10), followed by PLEC (n = 2), ITGB4 (n = 1), KRT5 (n = 1), and FERMT1 (n = 1). Laboratory examination revealed iron deficiency in 10 patients. One patient had moderate vitamin D deficiency, and five had mild vitamin D deficiency.
EB is a genetic disease that may associated with many systemic comorbidities. Multidisciplinary management of wound care is essential for the early management of severe EB to avoid wound progression into scars and deformities. The levels of vitamins such as ferritin and zinc, and the levels of hemoglobin and albumin, should be optimal levels to optimize wound healing.CancerAccessCare/ManagementAdvocacy -
Oncological Outcomes of Transoral Robotic Surgery and Neck Dissection Without Adjuvant Therapy in Patients With Low-, Intermediate-, and High-Risk Pathological Features in Oropharyngeal Carcinoma-An Institutional Experience.1 week agoPathologic risk features after transoral robotic surgery (TORS) inform the need for adjuvant therapy in oropharyngeal cancer (OPC); however, traditional risk stratification criteria may not fully apply to oropharyngeal carcinoma treated with TORS, especially for HPV+ disease.
The purpose of this study was to determine oncological outcomes including disease-free survival and overall survival in patients with intermediate-risk and high-risk histopathological features who underwent TORS without adjuvant radiation therapy.
We conducted a cohort study of patients with OPC, with intermediate-risk and high-risk pathological features who underwent primary TORS with neck dissection and without adjuvant treatment between 2015 and 2023 at the Princess Margaret Care Centre in Toronto, Canada.
Adult patients with a diagnosis of oropharyngeal carcinoma treated at the Princess Margaret Cancer Center/University Health Network between January 2015 and December 2023 were included in the study.
Transoral robotic surgical removal of primary oropharyngeal carcinoma with concurrent neck dissection.
Oncologic outcomes assessed included local, regional, and distant recurrence along with disease-free survival (DFS) and overall survival (OS).
Forty-two patients (27 male: 15 female; median age = 58) with 43 primary oropharyngeal cancers were included, of whom 33 (79%) were p16 positive. At a median follow-up of 49 months, 41 patients (98%) remained disease-free. Three patients (7%) developed second primaries in different sites that were successfully salvaged.
Patients with OPC treated with TORS alone have favorable oncologic outcomes, although second primary tumors remain a risk, likely related to field cancerization or multifocality.
Overall survival and locoregional control do not appear to be compromised in patients with OPSCC and adverse intermediate-to-high-risk features on histopathology who do not proceed to adjuvant therapy.CancerAccessAdvocacyEducation -
Healthcare providers' perspectives on implementing a primary care-based initiative to increase equitable bowel cancer screening participation in Australia.1 week agoBowel cancer is the fifth most common cancer in Australia and the second leading cause of cancer-related death. Although the National Bowel Cancer Screening Program mails test kits to eligible Australians, uptake remains suboptimal, particularly among underserved populations. The Alternative Access Model (AAM) is a primary care-based strategy through which healthcare providers (HCPs) distribute kits directly to eligible patients, enabling practitioner endorsement and patient navigation. This study explored HCPs' perceptions of the acceptability, feasibility, barriers, and enablers of implementing the AAM in general practices serving ethnically and socioeconomically diverse populations. Semi-structured interviews were conducted with primary HCPs in Melbourne, Australia. Nine general practice clinics participated in a two-phase study. Thirty-seven interviews were conducted with general practitioners (n = 13), practice nurses (n = 15), and practice managers (n = 9). Data were analysed using NVivo 15. Most participants (89%) were unfamiliar with the AAM. Once explained, the model was perceived as acceptable because it aligns with primary care's preventive role; however, implementation would be feasible only if barriers such as lack of financial incentives, system integration, and maintenance are addressed and provided. Improving equitable access requires more than making screening kits available. Tailored, culturally responsive, multi-faceted resources that could address perceived low bowel health literacy and cultural beliefs about screening, along with practitioners' endorsement and encouragement, and enhanced patient navigation within primary care are perceived having potential benefits in supporting more equitable bowel cancer screening participation among underserved populations.CancerAccessCare/ManagementPolicyAdvocacy
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The Prognostic Role of Vimentin Expression in Triple-Negative Breast Cancer: A Retrospective Cohort Study.1 week agoTriple-negative breast cancer (TNBC) is a subtype of breast cancer with the poorest prognosis and aggressive biological behavior. In Indonesia, approximately 15%-25% of breast cancer cases fall into the TNBC category. One of the biological markers involved in the epithelial-mesenchymal transition (EMT) process and tumor progression of TNBC is vimentin. Positive vimentin expression has been reported to correlate with reduced survival; however, data in the Indonesian population remain limited.
This retrospective study included 29 TNBC patients who received treatment at Dr. Cipto Mangunkusumo National General Hospital between 2017 and 2022, with a 3-year follow-up period. Clinicopathological data and vimentin expression were analyzed using bivariate analysis and Kaplan-Meier survival analysis.
Most patients were aged ≥ 40 years (82.8%), had a normal body mass index (82.8%), presented with locally advanced disease (72.4%), high histopathological grade (62.1%), and high Ki-67 expression (72.4%). A significant association was observed between vimentin expression and overall survival (p = 0.019), where increased vimentin expression was associated with reduced survival (mean survival 30.42 months in the negative group vs. 20.86 months in the positive group). Vimentin expression was also significantly associated with Ki-67 expression (p = 0.045), indicating a link between cellular proliferation and activation of EMT. Further analysis in patients with TNBC demonstrated that positive vimentin expression significantly increased the risk of mortality (p = 0.015; HR 5.64; 95% CI 1.39-22.7), while inadequate treatment was also associated with poorer overall survival (p = 0.011; HR 4.05; 95% CI 1.37-11.9).
Vimentin expression is significantly associated with reduced overall survival in patients with TNBC and correlates with high Ki-67 expression, reflecting tumor aggressiveness and activation of EMT. Inadequate treatment also contributes to poorer survival outcomes. These findings highlight the potential role of vimentin as a prognostic molecular marker in TNBC within the Indonesian population.CancerAccessAdvocacy -
Peripheral Lymphocyte Subsets Predict Efficacy and Overall Survival in Gastric Cancer Patients Receiving Preoperative Chemotherapy: A Retrospective Cohort Study.1 week agoPathologic complete response (pCR), which reflects the local immune status and preoperative chemotherapy efficacy, has garnered significant attention in gastric cancer research. However, the predictive value of peripheral lymphocyte subsets for pCR in gastric cancer patients receiving preoperative chemotherapy remains unclear.
This study aims to assess the correlation between preoperative peripheral lymphocyte subsets and pCR in gastric cancer patients.
In this retrospective study, gastric cancer patients who underwent curative gastrectomy following preoperative chemotherapy were included. Cytokines and peripheral lymphocytes were measured using flow cytometry. Clinicopathological characteristics, peripheral lymphocyte data and cytokine data were collected for the analysis. Overall survival (OS) was analyzed using Kaplan-Meier curves. Of 173 patients, 15 (8.7%) achieved pCR. A lower proportion of CD19+ B cells (7.5% vs. 10.4%, p = 0.008) was associated with pCR, and a high absolute count of NK cells was associated with better OS (p = 0.044).
Our study indicated that a lower proportion of CD19+ B cells may serve as a predictive biomarker for pCR, while an increased peripheral NK cell count could function as an auxiliary factor for risk stratification when combined with clinical parameters to assess long-term outcomes in gastric cancer patients receiving preoperative chemotherapy.CancerAccessCare/ManagementAdvocacy -
Intermediate OLGA/OLGIM Stages as Early Risk Markers for Gastric Cancer: A Systematic Review and Meta-Analysis.1 week agoThe Operative Link on Gastritis Assessment (OLGA) and Operative Link on Gastric Intestinal Metaplasia Assessment (OLGIM) systems stratify gastric cancer (GC) risk according to the extent of gastric atrophy and intestinal metaplasia. However, the clinical significance of intermediate stages remains uncertain.
To evaluate the association between OLGA/OLGIM stages and GC, with particular focus on the potential role of intermediate stages as early histological risk markers.
A systematic review and meta-analysis (PROSPERO CRD42024549931) was conducted according to PRISMA 2020 guidelines. Cohort, case-control, and cross-sectional studies reporting GC incidence or prevalence according to OLGA and/or OLGIM stage were included. Methodological quality was assessed using the Newcastle-Ottawa Scale and certainty of evidence using GRADE. Random-effects models were used to calculate pooled odds ratios (OR) and risk ratios (RR).
Twenty-eight studies involving 23,390 patients were included. Methodological quality was high and certainty of evidence was moderate. Advanced OLGA III-IV and OLGIM III-IV stages were strongly associated with GC (OR 6.49 and 7.76; RR 13.26 and 4.34, respectively). Intermediate stages were also associated with GC in observational studies: OLGA II (OR 2.77; 95% CI 1.83-4.20; I2 = 71%) and OLGIM II (OR 3.63; 95% CI 2.90-4.55; I2 = 0%). However, prospective cohort studies did not demonstrate a statistically significant increase in future GC incidence for OLGA II (RR 1.20; 95% CI 0.85-1.69).
Intermediate OLGA and OLGIM stages may represent early histological markers associated with gastric carcinogenesis. Prospective studies are required to determine their predictive value and potential implications for surveillance strategies, particularly in high-incidence populations.CancerAccessCare/ManagementAdvocacy -
Urinary Extracellular Vesicle-Associated EphA2 Predicts Intravesical Recurrence in Bladder Cancer.1 week agoTo examine the clinical usefulness of EphA2 detected on urinary extracellular vesicles (uEphA2) for bladder cancer detection and for estimating the risk of intravesical recurrence after transurethral resection of bladder tumor (TURBT).
An enzyme-linked immunosorbent assay was established to measure EphA2-positive urinary extracellular vesicles. The diagnostic cohort comprised 191 participants, including 120 patients with bladder cancer and 71 controls.
uEphA2 concentrations were higher in patients with bladder cancer than in controls. Receiver operating characteristic analysis yielded an area under the curve of 0.679, with 46.7% sensitivity and 87.3% specificity. Among patients evaluable for post-TURBT recurrence, high uEphA2 levels were associated with shorter intravesical recurrence-free survival. This association remained significant in multivariable Cox regression analysis after adjustment for the EORTC risk score and age.
uEphA2 showed modest diagnostic accuracy but high specificity and was independently associated with intravesical recurrence. These results support its potential use as a non-invasive urinary marker for post-TURBT risk stratification.CancerAccessCare/ManagementAdvocacy -
Using Joint Models in Phase I Dose-Finding Designs in Oncology: Considerations for Frequentist Approaches.1 week agoDose-finding trials for oncology studies are traditionally designed to assess safety in the early stages of drug development. With the rise of molecularly targeted therapies and immuno-oncology compounds, biomarker-driven approaches are increasingly importance. In this article, we propose a novel approach to dose-finding that incorporates biomarkers which predict for the subsequent development of clinical toxicity. The proposed joint model framework, which incorporates repeated biomarker measurements, is compared to the likelihood-based continual reassessment method (CRM) using only binary toxicity data, across various dose-toxicity relationship scenarios. Our findings highlight a critical limitation of likelihood-based approaches in early-phase dose-finding studies with small sample sizes: estimation challenges that have been previously overlooked in the phase I dose-escalation setting. We explore potential remedies to address these challenges and emphasize the appropriate use of likelihood-based methods. Simulation results demonstrate that the proposed joint model framework, by integrating biomarker information, can alleviate estimation problems in the likelihood-based CRM and improve the proportion of correct selection. However, we highlight that the inherent data limitations in early phase dose-finding studies remain a significant challenge that cannot be fully overcome in the frequentist framework.CancerAccessCare/ManagementAdvocacy
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The Lipid Line of Defence: Monounsaturated Fatty Acids (MUFAs) in Cancer and Ferroptosis.1 week agoMonounsaturated fatty acid (MUFA) metabolism promotes cancer progression and survival by regulating membrane lipid composition, maintaining lipid homeostasis and preserving redox balance. A growing body of evidence indicates that altered MUFA metabolism promotes tumour growth while protecting cancer cells from ferroptosis.
This review summarises current knowledge on the contributions of MUFA metabolism to carcinogenesis, regulation of ferroptosis and treatment response across different cancers. Further, we discussed the emerging treatment strategies targeting MUFA metabolic pathways.
Relevant experimental and clinical studies investigating MUFA metabolism, lipid metabolic reprogramming, ferroptosis and therapeutic interventions in cancer were comprehensively reviewed and critically analysed.
Enhanced de novo MUFA synthesis and incorporation into membrane phospholipids increase the MUFA-to-polyunsaturated fatty acid (PUFA) ratio, thereby reducing the availability of oxidation-prone PUFAs, limiting lipid peroxidation, and protecting cancer cells from ferroptosis. MUFA-driven membrane remodelling enhances membrane fluidity and activates oncogenic signalling pathways, including epithelial-mesenchymal transition (EMT), cancer cell migration, invasion and metastasis. These effects are mediated by the dysregulated expression of key lipogenic enzymes and signalling pathways that reprogramme lipid metabolism to meet the metabolic demands of cancer cells. Multiple studies have shown that MUFA metabolism is a promising therapeutic target. Furthermore, the inhibition of stearoyl-CoA desaturase-1 (SCD1) and fatty acid synthase (FASN), key enzymes in MUFA metabolism, sensitises cancer cells to ferroptosis by enhancing lipid peroxidation.
MUFA metabolism is a key regulator of cancer progression and ferroptosis resistance. Targeting MUFA metabolic pathways is a promising therapeutic strategy. However, mechanistic studies are required to elucidate the molecular mechanisms underlying sensitivity to ferroptosis and to optimise clinical applications.CancerAccessCare/ManagementPolicy -
A new era of research in the U.S. Department of War Serum Repository: a review of published studies, 2013-2024.1 week agoThe Department of War Serum Repository (DOWSR, formerly DODSR1) was established in 1989 after the initiation in 1985 of the U.S. Department of War's universal mandatory human immunodeficiency virus (HIV) screening program. DOWSR, which is currently maintained by the Armed Forces Health Surveillance Division (AFHSD), preserves over 78 million serum specimens. Similar to a study that investigated research conducted from 1985 through 2012 utilizing the serum repository, this study evaluated DOWSR specimen availability, stratified by demographic variables, and conducted an analysis to determine total number and types of research studies performed using the DOWSR from 2013 through 2024. Two methods were employed: a structured PubMed search and an exhaustive online search based on records of requests for serum samples from AFHSD. Results show that the focus of DOWSR's research within the past decade has increased, especially in regulatory molecules, autoimmune indicators, and microRNA expression patterns, with increases in both the number of sponsored studies and variety of analytes investigated. Changes in the types of studies pursued by DOWSR research may reflect changing trends in funded research regarding health concerns for service members and veterans. This review identified 112 published and 21 non-published studies that used DOWSR sera during the study period. Of the published 112 studies, 30 investigated infectious diseases, 25 investigated autoimmune disorders, 13 investigated neoplasms, and 11 investigated chronic metabolic outcomes. More studies using DOWSR specimens were published on environmental exposures and autoimmune disorders compared to prior years.CancerAccessCare/Management