Background: Non-nutritive sweeteners (NNS) are chemical substances developed by the food industry to reduce sugar and calories while preserving sweetness. Epidemiological studies have indicated a potential increased risk of certain cancers, including breast cancer (BC), associated with NNS consumption. However, the evidence has exclusively relied on self-reported dietary information rather than objective measurements of NNSs. We examined the association of urinary concentrations of NNS with BC risk in women from the large Moli-sani Study. Methods: Using a case-cohort design, a sample of 988 middle-aged women (mean age 55 ± 12 y) was randomly selected as a sub-cohort and compared to 272 women with incident BC (38 premenopausal and 234 postmenopausal). A total of 6 commonly used NNSs (i.e., aspartame, acesulfame, saccharin, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography-mass spectrometry in spot urine samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005-2010). The multivariable hazard ratios (HRs) were estimated using weighted Cox regression models for the case-cohort design, with each NNS modelled as a binary variable (i.e., presence vs. absence). The sum of these values produced a total urinary NNS score, which could range from 0 to 6, and was further categorised as low (0-1) or high (2-5). Results: The predominant NNS detected in urine was saccharin (E954), contributing to 77% of total NNSs, followed by steviol glycosides (E960;11%). In multivariable-adjusted Cox analyses, neither individual NNSs nor total NNS urinary concentrations were associated with overall BC risk (HR = 1.09; 95% CI 0.80-1.48 for high vs. low). However, the presence of sucralose (E955) was directly linked to premenopausal BC (HR = 5.90; 95% CI 1.44-24.20; p = 0.014), although this estimate was based on only 38 cases and was imprecise. Conclusions: Urinary NNS concentrations were not associated with overall BC risk. The observed association between urinary sucralose and premenopausal BC should be considered exploratory and hypothesis-generating and requires independent replication.

Photodynamic therapy (PDT) offers spatially confined, repeatable and mechanistically orthogonal tumor control, yet its broader clinical impact remains limited by inadequate light access, oxygen dependence and incomplete biological selectivity. Boron-dipyrromethene (BODIPY) dyes provide an unusually programmable platform for addressing these constraints. Although native BODIPYs are fluorescence-biased and inefficient triplet photosensitizers, their absorption, intersystem crossing, reactive oxygen species identity, aggregation, targeting and activation can be independently engineered through modular scaffold modification. In this Review, we present BODIPY as a programmable photochemical chassis for precision-oriented PDT. We first define the structure-photophysics-function relationships that convert BODIPY fluorophores into red- or near-infrared-responsive, type I- or type II-tunable and formulation-compatible photosensitizers. We then introduce a tumor-context-adaptive framework that integrates light-delivery routes, oxygen economy, multiscale targeting, organelle vulnerability and microenvironment-locked activation. Finally, we examine how BODIPY PDT can extend beyond direct cytotoxicity to vascular remodeling, immunogenic cell death, the potential to support in situ vaccination and rational combination therapy, while proposing translational go/no-go criteria for clinically credible candidates. We argue that progress will depend less on molecular complexity than on indication-first co-design of BODIPY chemistry, tumor biology and deployable light hardware.

Background and Objectives: Gastric cancer is one of the most common malignancies worldwide and continues to be associated with high mortality. The hemoglobin-to-red cell distribution width (HGB/RDW) ratio has emerged as a promising hematological prognostic biomarker in various cancers. However, its prognostic significance in patients with curative-intent resection of non-metastatic gastric cancer remains insufficiently investigated. This study aimed to evaluate the association between the pretreatment HGB/RDW ratio and progression-free survival (PFS) as well as overall survival (OS) in patients with non-metastatic gastric cancer. Materials and Methods: In this multicenter study, a total of 175 patients with non-metastatic gastric cancer who received perioperative FLOT chemotherapy (four preoperative and four postoperative cycles) and underwent curative-intent surgical resection were retrospectively analyzed. A cut-off value for the HGB/RDW ratio was calculated using receiver operating characteristic (ROC) curve analysis. Survival outcomes, including progression-free survival (PFS) and overall survival (OS), were analyzed using the Kaplan-Meier method. Multivariate Cox proportional hazards regression analysis was performed to identify independent prognostic factors. Results: Patients with an HGB/RDW ratio > 0.85 demonstrated significantly superior 2-year and 5-year OS rates (76.2% vs. 59.6% and 51.6% vs. 27.7%, respectively; p = 0.003) and PFS rates (69.4% vs. 49.6% and 53.7% vs. 36.4%, respectively; p = 0.047) compared to those with HGB/RDW ≤ 0.85. Multivariate analysis identified HGB/RDW ≤ 0.85 as an independent predictor of both increased mortality risk (HR: 1.88, 95% CI: 1.16-3.06; p = 0.011) and disease progression risk (HR: 1.79, 95% CI: 1.18-2.72; p = 0.006). Conclusions: The pretreatment HGB/RDW ratio is an independent prognostic factor for OS and PFS in patients with curative-intent resection of non-metastatic gastric cancer and may be considered a practical marker that could contribute to treatment planning in this patient population.

Background and Objectives: End-of-life care in oncology demands a holistic, multidisciplinary framework that pivots clinical priorities from disease-directed therapies toward symptom optimization, comfort, and patient dignity. Within this context, the present study investigated care delivery patterns among advanced cancer patients during their final week of life. Materials and Methods: A retrospective medical record review was conducted, comparing an oncology ward, an intensive care unit, an inpatient palliative unit, and a home-based palliative care setting. We analyzed aggressive interventions, end-of-life care pathways, symptom management, medication use and rationalization, and transitions between care settings. Results: Among the 306 patients studied, diagnostic testing and artificial hydration were universally administered in the oncology and intensive care unit (p < 0.001), where prescriptions focused primarily on pain management. Conversely, palliative care settings addressed a wider range of terminal symptoms. The rationalization of non-essential medications took place between 1.8 and 2.9 days before death, varying significantly across medication classes and clinical settings (p < 0.001). Additionally, intensive care unit admissions were more prevalent among patients with advanced cancer, while home-based patients underwent the greatest number of care transitions. Conclusions: These findings highlight substantial differences in care across settings, emphasizing the need for coordinated planning, continuity, and patient-centered approaches to ensure comfort and dignity in the final week of life.

Background and Objectives: Intra-corporeal esophagojejunostomy after totally laparoscopic total gastrectomy (TLTG) remains one of the most technically demanding steps of minimally invasive gastric surgery. The management of the common entry hole in linear stapler-based reconstructions still relies on advanced intra-corporeal suturing. The sutureless L-shape esophagojejunostomy with endoscopic assistance (SLEJ) technique, previously described by our group, was developed to overcome this limitation by combining an L-shaped linear stapler configuration with intraoperative endoscopic quality control. Building upon our initial results on the perioperative feasibility of the technique, the present study aimed to evaluate its intermediate-term anastomotic, functional, and oncological outcomes. Materials and Methods: Patients who underwent TLTG with D2 lymph node dissection and SLEJ reconstruction for gastric cancer between July 2024 and January 2026 were evaluated. Eligibility criteria included a minimum postoperative follow-up of six months, clinical and endoscopic surveillance, and complete contrast-enhanced thoraco-abdominopelvic computed tomography records. Protocol-based upper gastrointestinal endoscopy was performed at six-month intervals irrespective of symptoms to objectively assess anastomotic lumen width, mucosal healing, reflux findings, and possible intraluminal recurrence. The primary endpoint was anastomosis complication-free survival (anastomotic stenosis, alkaline reflux/reflux esophagitis, marginal ulcer, bleeding due to ulceration, and intraluminal recurrence); secondary endpoints were disease-free survival (DFS), local recurrence and changes to nutritional status. Results: A total of 26 patients (18 men and 8 women; mean age 59.0 ± 7.8 years) were analyzed. Anastomotic stricture developed in two patients and was successfully managed with two sessions of endoscopic balloon dilation in both. Similarly, alkaline reflux was documented in two additional patients and resolved under medical treatment. None of the patients required surgical revision. The mean ACFS follow-up duration was 12.42 months with ACFS rates of 92.3% at six months and 81.1% from the twelfth month onward. No local anastomotic recurrence was detected during follow-up. Disease progression occurred in four patients (15.4%), presenting as distant organ metastasis (n = 2) or peritoneal carcinomatosis (n = 2). The mean DFS follow-up duration was 12.62 ± 6.18 months, and the twelve-month OS and DFS rates were 82.1% and 84.0%. Postoperative body weight decreased significantly compared with preoperative values (76.69 ± 15.59 kg vs. 63.23 ± 10.55 kg; p < 0.001). A significant decrease was observed in the mean SMI between the preoperative and follow-up assessments (p < 0.001). The mean preoperative SMI was 49.90 ± 9.04 cm²/m², compared with 44.53 ± 7.98 cm²/m² at follow-up. No statistically significant changes were observed between the preoperative and follow-up periods for serum albumin and PNI variables (p = 0.703 and p = 0.970). Conclusions: The present intermediate-term analysis suggests that the SLEJ technique is feasible and associated with acceptable intermediate-term anastomotic, functional, and oncological outcomes in this preliminary single-center cohort. By standardizing common entry-hole management without intra-corporeal suturing and incorporating intraoperative endoscopic quality control, the technique offers a feasible alternative to established linear stapler-based reconstructions.

Background and Objectives: Malignant double obstruction, defined as the coexistence of malignant biliary obstructio (MBO) and malignant gastric outlet obstruction (mGOO), frequently complicates advanced pancreatic and periampullary malignancies. Because biliary and duodenal obstructions are anatomically and functionally interconnected, treatment of one may influence the outcome of the other. This review aims to summarize current evidence on endoscopic management strategies and to propose an anatomy-driven approach integrating conventional and endoscopic ultrasound (EUS)-guided techniques. Materials and Methods: A narrative review of the current literature was performed, focusing on endoscopic approaches for malignant biliary and gastric outlet obstruction. Available evidence regarding endoscopic retrograde cholangiopancreatography (ERCP), EUS-guided biliary drainage (EUS-BD), enteral self-expandable metal stenting, and EUS-guided gastroenterostomy (EUS-GE) was critically analyzed, focusing on technical feasibility, clinical outcomes, adverse events, and therapeutic sequencing. Results: ERCP remains an effective option when papillary access is preserved; however, duodenal obstruction, especially when involving the papilla, represents a major limitation. EUS-BD has emerged as a reliable alternative after failed ERCP and may provide a primary drainage strategy in selected patients. In the setting of concomitant gastric outlet obstruction, EUS-guided hepaticogastrostomy may offer advantages over choledochoduodenostomy by avoiding the obstructed duodenal pathway. For malignant gastric outlet obstruction, enteral stenting provides rapid symptom relief, but is associated with limited long-term durability. EUS-GE has demonstrated high technical and clinical success rates, lower rates of recurrent obstruction compared with enteral stenting, and outcomes comparable to surgical gastrojejunostomy with reduced invasiveness. These findings support an integrated EUS-based approach for selected patients. Conclusions: Malignant double obstruction should be considered a single anatomofunctional entity rather than two independent conditions. An individualized, anatomy-driven strategy combining EUS-guided biliary drainage and EUS-GE may represent the future direction of endoscopic palliation, allowing durable internal bypass and facilitating oncological management. Further prospective studies are required to define optimal treatment sequencing and patient selection.

Background and Objectives: Tumor regression grade (TRG) in gastric cancer patients treated with neoadjuvant/perioperative chemotherapy is increasingly recognized as an important indicator of treatment efficacy and long-term prognosis. However, in geriatric patients, data on neoadjuvant therapy and on the relationship between pathological response and survival remain limited. In this study, we investigated the prognostic significance of pathological response, assessed according to Becker's TRG in geriatric patients with locally advanced gastric adenocarcinoma who received neoadjuvant/perioperative chemotherapy and underwent gastrectomy. Materials and Methods: We retrospectively analyzed 82 patients aged ≥65 years with histologically confirmed gastric adenocarcinoma who received neoadjuvant/perioperative chemotherapy followed by curative gastrectomy at a single center between 2017 and 2024. Pathological response was evaluated using the Becker tumor regression grading (TRG) system and classified as good (TRG 1-2) or poor (TRG 3). Clinicopathological features, treatment characteristics, disease-free survival (DFS), and overall survival (OS) were compared between groups. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test. Univariable and multivariable Cox proportional hazards models were used to assess the prognostic impact of TRG and other clinicopathological factors on DFS and OS. Results: The study included 82 geriatric patients, of whom 50 (61.0%) showed a good pathological response (TRG 1-2), while 32 (39.0%) showed a poor pathological response (TRG 3). Poor response was more frequently seen in clinical stage III disease and was accompanied by a higher rate of lymphovascular invasion. Median DFS was 42.4 months in the good response group versus 13.0 months in the poor response group (p < 0.001), and median OS was 47.7 and 15.5 months, respectively (p < 0.001). In multivariable analysis, ECOG performance status (HR 2.697; 95% CI 1.381-5.269; p = 0.004), lymphovascular invasion (HR 4.960; 95% CI 1.545-15.919; p = 0.007), and poor pathological response (HR 2.066; 95% CI 1.055-4.045; p = 0.034) remained independent predictors of DFS. For OS, ECOG performance status (HR 2.719; 95% CI 1.398-5.290; p = 0.003), lymphovascular invasion (HR 4.448; 95% CI 1.400-14.132; p = 0.011), and poor pathological response (HR 2.311; 95% CI 1.161-4.601; p = 0.017) remained independent predictors of OS. Conclusions: Our study suggests that pathological response assessed by the TRG system is a valuable prognostic marker in geriatric gastric adenocarcinoma. Good pathological response was associated with longer DFS and OS, while poor pathological response remained an independent predictor of both shorter DFS and OS.

Background and Objectives: Deciding which pigmented or non-pigmented skin lesions require surgical excision, as opposed to continued observation, is a common challenge in everyday dermatologic practice. Although dermoscopy is well established as a tool that improves melanoma detection accuracy compared with naked-eye examination, real-world evidence on how demographic profile, patient history, and dermoscopic impression jointly influence the surgical decision remains limited. This study examined the clinical and dermoscopic factors associated with a positive surgical decision (PSD) in a large single-centre screening cohort. Materials and Methods: This retrospective cross-sectional analysis included 643 consecutive patients (415 female (64.5%), 228 male (35.5%); mean age 51.3 ± 16.8 years) undergoing dermoscopic skin cancer screening. Data recorded included family history of melanoma (FHM), personal history of skin cancer (HSC), childhood sunburn (CS), clinically atypical lesions (CAL), suspicion of basal/squamous cell carcinoma (BCC/SCC), nevus count (NC, 0-4), and the surgical decision (PSD). Free-text dermoscopic descriptions were grouped into seven diagnostic categories. Group comparisons used the Mann-Whitney U, χ², and Fisher's exact tests; predictors of PSD were characterised using multivariable logistic regression (with Hosmer-Lemeshow and Nagelkerke R² statistics), multiple correspondence analysis (MCA), Gower-distance k-medoids clustering, and receiver operating characteristic (ROC) analysis, including the area under the curve (AUC). Missing NC data (13.2%) were assessed using Little's test for data missing completely at random (MCAR test). Results: A positive surgical decision was recorded in 133/643 patients (20.7%) and was significantly more common in men than women (25.9% vs. 17.9%; p = 0.017; corresponding to an odds ratio (OR) of 1.61). In multivariable analysis, suspicion of BCC/SCC (OR = 24.7, 95% confidence interval (CI): 9.26-66.0) and clinically atypical lesions (OR = 5.53, 95% CI 3.50-8.74) were the strongest independent predictors of PSD (Nagelkerke R² = 0.31; Hosmer-Lemeshow p = 0.977), far outweighing family or personal history. A significant interaction between childhood sunburn and nevus count (OR = 1.39, 95% CI 1.16-1.66; p < 0.001) predicted clinical atypia. Missing NC data were consistent with a completely random pattern (Little's χ² = 2.80, df = 2, p = 0.247). Dermoscopic impression showed strong discriminative value for PSD: "no concern" had the highest negative predictive value (NPV = 0.927; AUC = 0.762), while "atypical lesion" combined high specificity (0.916) and positive predictive value (0.632; AUC = 0.736). On average, 4.8 patients were examined for every surgical referral generated (a screening-to-referral ratio, not a number needed to screen for a histologically confirmed cancer). Conclusions: Surgical decision-making in this cohort was driven almost exclusively by the dermoscopic impression-suspected BCC/SCC and clinical atypia-rather than by family or personal oncological history, while male sex was independently associated with a higher surgical rate. These findings support dermoscopy-led triage protocols and highlight the potential value of standardised risk stratification to optimise referral pathways in routine skin cancer screening.

To compare a commercially available artificial intelligence (AI) risk-classification system with PI-RADS for detecting clinically significant prostate cancer (csPCa) on prostate MRI.

This retrospective multicentre, multivendor diagnostic accuracy study included men who underwent prostate MRI and histopathologic verification between 2014 and 2025. Index tests were DeepHealth Prostate Suite AI risk category and radiologist-assigned PI-RADS; the reference standard was International Society of Urological Pathology Grade Group ≥ 2. Patient-level non-inferiority testing, receiver operating characteristic analysis, lesion-level free-response receiver operating characteristic analysis, and patient-level bootstrap confidence intervals were used. Workflow support analyses modeled biopsy-avoidance strategies and AI-based risk stratification within PI-RADS 3 lesions.

After exclusions, 787 men (median age, 70 years; interquartile range, 64-75) were evaluated; 380 (48.3%) had csPCa. AI sensitivity was non-inferior to PI-RADS at the patient level (97.6% vs 92.6%; p < 0.001) but not at the lesion level (78.8% vs 88.8%; p = 0.98). Patient-level area under the curve was higher for AI than PI-RADS (0.80 vs 0.77; difference, 0.032; 95% confidence interval, 0.001-0.064; p = 0.043). A targeted PI-RADS 3 strategy avoided 18.9% of biopsies while maintaining 98.4% sensitivity. Among PI-RADS 3 lesions, AI upgraded 93.1% of csPCa-positive lesions and assigned a low risk to 24.1% of benign lesions.

The AI system was non-inferior for patient-level sensitivity but not lesion-level sensitivity. AI risk classification is best positioned as decision support for biopsy triage, particularly in PI-RADS 3 lesions.

Question Can three-tier artificial intelligence risk classification support prostate MRI biopsy triage in men while preserving detection of clinically significant prostate cancer? Findings Artificial intelligence had non-inferior patient-level sensitivity and higher patient-level discrimination than PI-RADS, but lower lesion-level sensitivity at the predefined threshold. Clinical relevance Artificial intelligence risk categories can complement PI-RADS by supporting high-sensitivity biopsy triage, especially for equivocal PI-RADS 3 lesions, while radiologists retain responsibility for lesion mapping.

To present the 2025 revision of the Japan Society of Gynecologic Oncology Clinical Practice Guidelines for the treatment of ovarian, fallopian tube, and primary peritoneal cancers, which incorporates recent advances in surgical strategies, molecular diagnostics, and maintenance therapies within the context of the Japanese healthcare system. Clinical questions (CQs) were formulated using the PICO framework. Systematic literature searches were conducted in PubMed, the Japan Medical Abstract Society, and the Cochrane Library (January 2019-December 2023), along with additional manual searches for emerging evidence. Three new systematic reviews addressing minimally invasive surgery, secondary cytoreductive surgery, and lymphadenectomy for malignant germ cell tumors were performed. Evidence levels and recommendation strengths were determined according to the Minds 2020 methodology adapted to the Japanese clinical and insurance environment. Recommendations were formulated using a modified GRADE approach. Final recommendations were established through multidisciplinary consensus voting, with a predefined agreement threshold of 75%. The sixth edition comprises 6 chapters and 49 CQs. Major updates include expanded guidance on homologous recombination deficiency testing and genomic profiling, refined indications for maintenance therapy with poly(ADP-ribose) polymerase (PARP) inhibitors and bevacizumab, clarified recommendations for secondary cytoreductive surgery, updated management of PARP inhibitor-exposed recurrence, and strengthened sections on onco-fertility and palliative care. Transparency was enhanced by disclosing key discussion points and consensus rates for each recommendation. These guidelines define evidence-based standards tailored to Japanese clinical practice while maintaining international relevance. They aim to reduce inter-institutional disparities, optimize patient outcomes, and provide a transparent framework for future therapeutic integration.