Background: Curative-intent management of locally recurrent rectal cancer (LRRC) generally comprises neoadjuvant therapy and surgery. In patients with unresectable LRRC, where surgical intervention is not feasible, management is limited to non-operative bimodality therapy with systemic therapy and radiotherapy. Evidence guiding the optimisation of non-operative management remains limited. In this context, the therapeutic goal is to achieve prolonged local control while minimising treatment-related adverse events and preserving quality of life. Radiotherapy dose escalation has been proposed as a potential strategy to achieve this balance. However, its feasibility and safety in the non-operative management of unresectable LRRC have not yet been established. As such, this study aims to evaluate the feasibility and safety of this radiotherapeutic approach, and to determine its impact on both symptom control and oncological outcomes. Methods: This prospective, multicentre, single-arm feasibility study will enrol 30 patients with unresectable or inoperable LRRC without distant metastases, or with (oligo)metastatic disease not requiring immediate systemic therapy. Previously irradiated patients will undergo reirradiation with stereotactic body radiotherapy (re-SBRT; 5 & times; 9 Gy) when feasible, or, alternatively hyperfractionated chemo-reirradiation (50.4 Gy in 1.2 Gy twice-daily fractions with concurrent capecitabine). Radiotherapy-na & iuml;ve patients will receive chemoradiotherapy with a simultaneous integrated boost (25 & times; 2.6 Gy, EQD2Gy alpha/beta=5Gy of 71 Gy with concurrent capecitabine). [1] The primary endpoint is treatment regimen feasibility, defined as grade >= 3 acute radiotherapy-related adverse events (CTCAE version 5.0) occurring in no more than seven patients (23%). Secondary endpoints include late adverse events, quality of life and symptom control, and 1-and 3-year progression-free survival, disease-free survival, and overall survival. Discussion: This protocol describes the STEP-UP study, which will determine the feasibility of radiotherapy dose escalation in unresectable LRRC. If feasible and safe, this approach could provide an effective treatment intensification strategy to improve local control and symptom burden in patients with unresectable LRRC, addressing a major unmet clinical need. Trial registration: ClinicalTrials.gov: NCT07721181 Overview of Medical-Scientific Research in the Netherlands (OMON) Registry: NL-011150. International Clinical Trial Registry Platform (ICTRP): NL-OMON61161.
To estimate major clinical event rates for patients with atrial fibrillation (AF) and atherosclerotic disease treated with edoxaban in routine practice, and to evaluate how well such patients were represented in ENGAGE AF-TIMI 48, the seminal randomized trial comparing edoxaban against warfarin for AF. ETNA-AF-Europe is a prospective cohort of AF patients receiving edoxaban in routine care. We compared patients with coronary or peripheral artery disease (CAD/PAD) to: (1) those without CAD/PAD in ETNA-AF-Europe, and (2) CAD/PAD patients in ENGAGE AF-TIMI 48. Of 13,164 patients in ETNA-AF-Europe, 23.3
Oral leukoplakia (OL) is a precancerous condition typically assessed through histopathological examination of mucosal lesion biopsies. Identifying histological features of oral lichenoid lesions (OLL) within OL samples is clinically important, as they influence the risk of malignant transformation and may indicate oral lichen planus (OLP). However, interpretation is challenging, with substantial intra- and inter-observer variability. Artificial intelligence (AI) offers the potential to provide reproducible, objective support for histopathological classification. We developed an AI system to (a) segment histological layers and extract characteristics of the keratinization zone, (b) classify keratinization types, and (c) distinguish OL from OLL. A retrospective cohort of 240 histological slides from 192 patients was included. Of these, 175 transversely sectioned slides underwent manual segmentation of subepithelium, epithelium, keratinization zone, and nuclei in the keratinization zone. Measurements of keratin thickness and nuclei density were performed to classify the keratinization zone into (hyper)orthokeratosis, parakeratosis, or hyperparakeratosis. All 240 slides were labeled as OL or OLL and crops were extracted for diagnosis classification. Segmentation was evaluated with Dice–Sørensen coefficient (DSC), and classification was evaluated by accuracy. Segmentation of histological layers was highly effective (DSC > 0.92), with lower performance for nuclei (DSC = 0.68). Keratinization classification reached 0.92 accuracy: (hyper)orthokeratosis 0.98, hyperparakeratosis 0.93, parakeratosis 0.94. Lesion-level OL/OLL classification achieved 0.929 accuracy, with slightly better effectiveness in transverse sections than tangential sections (0.944 vs. 0.925). The AI system demonstrated strong segmentation and classification capabilities, supporting its potential to enhance diagnostic accuracy, reproducibility, and efficiency for the assessment of OL samples.
This study evaluates incisional hernia incidence 13 years after accrual ended. QuestionDoes small-bites fascial closure reduce the long-term incidence and severity of incisional hernias compared with large-bites closure after elective midline laparotomy?FindingsIn this multicenter randomized trial with median follow-up of 8 years (maximum 15 years), cumulative incidence of incisional hernia at 13 years was 34% in the small-bites group vs 49% in the large-bites group. Hernias in the small-bites group were smaller and quality of life was lower in patients with an incisional hernia.MeaningSmall-bites fascial closure significantly reduced long-term incidence and size of incisional hernia and should be considered standard practice. ImportanceIncisional hernia after midline laparotomy causes long-term morbidity and reduced quality of life; closure technique may affect long-term risk. Superiority of the small-bites fascial closure technique in reducing incisional hernia rate at 1 year after midline laparotomy was previously demonstrated in the STITCH trial.ObjectiveTo evaluate incisional hernia incidence 13 years after accrual ended.Design, Setting, and ParticipantsThis multicenter, double-blind randomized clinical trial took place between October 2009 and March 2012 at 10 participating centers in the Netherlands, including surgical and gynecological departments. The study included 559 patients undergoing elective midline laparotomy. These data were analyzed from January 2025 through June 2025.InterventionsContinuous small-bites fascial closure (5 mm & times; 5 mm, polydioxanone 2-0 on 31-mm needle) vs large bites (10 mm & times; 10 mm, looped polydioxanone on 48-mm needle) in the control group.Main Outcomes and MeasuresPrimary outcome was cumulative incidence of incisional hernia (clinical and radiologic) analyzed with time-to-event methods accounting for competing risks. Secondary outcomes included hernia width, repair rates, and patient-reported quality of life.ResultsA total of 275 patients were randomized to small-bites fascial closure and 284 to the control group. Median time to censoring was 8 (IQR, 2-13) years. At final follow-up, 170 patients were alive without evidence of incisional hernia. Of these, 122 (72%) underwent additional abdominal ultrasound. Abdominal imaging performed as part of patient care was available for 238 patients. At 13 years, cumulative incidence of incisional hernia was 34% in the small-bites group and 49% in the large-bites group (hazard ratio, 0.61; 95% CI, 0.43-0.86). Corresponding outcomes for hernia width more than 20 mm were 17% and 34%, respectively (hazard ratio, 0.36; 95%CI, 0.21-0.60). Hernias were significantly smaller after small-bites closure at final follow-up (mean, 25 mm vs 43 mm; P = .02). Hernia repair rates were similar. Patients with an incisional hernia reported significantly lower quality of life.Conclusions and RelevanceIn this study, the small-bites technique reduced the long-term risk and width of incisional hernias after elective midline laparotomy. Given its simplicity, cost neutrality, and broad applicability, it should be regarded standard practice. Further research should explore strategies to enhance adoption and assess broader patient-centered outcomes.Trial RegistrationClinicalTrials.gov Identifier: NCT01132209
To optimize surveillance in individuals with a family history (FH) of colorectal cancer (CRC), knowledge on the incidence rate of non-advanced adenomas (nAAs) and their progression rate to advanced neoplasia (AN) is crucial. We jointly estimated personalized adenoma incidence and progression rates using a novel statistical approach. We used data of individuals with ≥ 1 first-degree relative with CRC who underwent ≥ 2 colonoscopies (n = 876 individuals; n = 2384 colonoscopies). Interval-censored data on timing and yield (no adenomas/nAA/AN) of each colonoscopy were available. nAA incidence and progression time from nAA to AN were estimated using a Bayesian progressive three-state model. Over a median follow-up of 6 years (interquartile range 5–6), 60 (6.8
