Search Results (1,159)

Aflatoxins, particularly aflatoxin B₁ (AFB₁), are among the most potent naturally occurring carcinogens and remain a major food-borne hazard in parts of Asia and Africa. China has generated a uniquely cohesive body of evidence connecting aflatoxin contamination to hepatocellular carcinoma (HCC), especially in settings where chronic hepatitis B virus (HBV) infection is highly prevalent and acts synergistically with aflatoxin exposure. Over five decades, field investigations and laboratory innovations—exemplified by long-term work in Qidong—have assembled a multi-layered causal chain spanning the following: (i) contamination monitoring in staple foods; (ii) quantification of internal dose and biologically effective dose using validated biomarkers (e.g., urinary AFB₁–N⁷–guanine, AFM₁, and serum AFB₁–lysine albumin adducts); (iii) a characteristic molecular fingerprint in tumors and circulation (TP53 R249S); (iv) reversibility demonstrated through randomized intervention trials and policy-driven natural experiments. Chemoprevention and dietary interception studies (e.g., oltipraz, chlorophyllin, and broccoli sprout beverages) showed that enhancing detoxication pathways can lower biomarker burdens in exposed populations. At the population level, a sustained dietary transition from maize to rice, together with strengthened food governance, was accompanied by marked decreases in biomarker distributions and subsequent declines in HCC mortality in endemic regions. Nevertheless, regional heterogeneity, multi-mycotoxin co-exposure, and climate variability are expected to increase exposure volatility and complicate surveillance. Here, we translate and synthesize the Chinese evidence base, highlight biomarker-enabled monitoring and policy evaluation, and propose an integrated “5+1” prevention framework spanning source control, process detoxification, tiered governance, short-course interception, precision follow-up of high-risk individuals, and climate-sensitive early warning along the climate–agriculture–storage–processing–population (CAT–CSPP) chain. Full article

Background: Desmoid tumors (DTs) are rare, locally aggressive fibroblastic neoplasms with highly heterogeneous clinical behavior. The present work constitutes the second part of a two-part project, following our previously published multidisciplinary review of the diagnostic and therapeutic landscape of DTs. It provides a comprehensive analysis of our institutional experience as a national reference center for sarcoma. We aim to describe real-world diagnostic pathways, management strategies, and clinical outcomes in a high-volume cohort. Methods: We conducted a retrospective cohort study that included patients diagnosed with DT at our center between 2014 and 2024. Demographic, clinical, molecular, treatment, and outcome data were collected. Management strategies were analyzed according to tumor location, symptoms, progression patterns, and multidisciplinary decision-making. Outcomes included response rates, event-free survival (EFS), need for active treatment, response to systemic therapy, and recurrence after local treatments. Results: A total of 109 patients were included (median age 36.8 years; 56.9% women). Somatic CTNNB1 mutations were identified in 23 of 29 tested patients, predominantly T41A, while germline alterations were found in 18 patients, mainly in APC. Initial management was conservative in 40.4% of patients and active in 59.6%, primarily through surgery. After a median follow-up of 41.5 months, 44.9% of patients experienced disease progression. Among patients managed with active surveillance, spontaneous regression occurred in 22.2%, and 58% remained treatment-free. Surgical relapse occurred in 35.8% of patients undergoing upfront resection, with major postoperative complications limited to externally operated cases. Cryoablation achieved radiological responses in most evaluable patients, while systemic therapies showed clinical activity but relevant toxicity, particularly with tyrosine kinase inhibitors. The median EFS for the whole cohort was 57 months. Conservative initial management and R1/2 surgical margins were independently associated with worse EFS. Conclusions: Our results support a personalized, multidisciplinary management strategy for DTs, prioritizing conservative approaches when appropriate and reserving active treatments for progressive or symptomatic disease. Outcomes achieved in a specialized referral center are comparable to those reported in large international retrospective series, underscoring the value of expert multidisciplinary care in optimizing DT management. Full article

Background/Objectives: Peritoneal surface metastases (PSMs) from colorectal cancer have high rates of peritoneal recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior studies dichotomize peritoneal recurrence into “early” and “late,” limiting insight into how clinicopathologic factors influence recurrence timing. This study aimed to identify predictors of peritoneal recurrence and quantify their continuous association with time to recurrence following CRS/HIPEC. Methods: Patients undergoing CC-0 CRS/HIPEC for colorectal PSM from 2018 to 2024 were identified from a prospectively maintained database. The primary outcome was peritoneal surface recurrence. Variables included peritoneal cancer index (PCI), tumor location, histology, HIPEC regimen, and KRAS/BRAF/SMAD4 status. Factors with p < 0.10 on univariable analysis were entered into multivariable logistic regression (recurrence: yes/no) and linear regression (time to recurrence). Results: Among 133 patients, 64 (48.1%) developed peritoneal recurrence. Median time to recurrence was 41.4 weeks (IQR 24.9–74.0), and PCI was higher among those who recurred (median 11.0 vs. 5.0, p < 0.01). Neither tumor stage, histology, intraperitoneal chemotherapy agent, nor molecular alterations were associated with increased risk of peritoneal recurrence. When controlling for PCI, right- and sigmoid-colon primaries independently predicted peritoneal recurrence compared to all other locations without influence on recurrence timing (right: OR 7.18; sigmoid: OR 6.54; p < 0.01). Among patients who recurred, each one-point increase in PCI corresponded to a 2.43-week earlier relapse (p < 0.01). Conclusions: Nearly half of patients with colorectal PSM recurred despite complete CRS/HIPEC. Tumor location predicted peritoneal recurrence, while PCI independently shortened time to relapse. Modeling PCI as a continuous predictor refines postoperative risk stratification and may inform individualized surveillance strategies. Full article

Reticuloendotheliosis virus (REV) is an immunosuppressive virus in poultry that can cause acute reticular neoplasms, chronic lymphoid tumors, stunting syndrome, and secondary infections. In many countries, the lack of effective vaccines has resulted in a high prevalence of REV infections and substantial economic losses. Enzyme-linked immunosorbent assay (ELISA)-based antibody detection is an important tool for monitoring the REV prevalence in poultry farms. ELISA coating antigens generally consist of either whole virus or viral protein; however, most commercially available REV antibody ELISA detection kits use whole virus as the coating antigen, which limits their applicability in certain diagnostic and research settings. In this study, the gp90 protein from a dominant REV strain was expressed and purified using 293F suspension cell eukaryotic expression system. Using recombinant gp90 protein as the coating antigen, an indirect ELISA for detecting gp90 antibodies (gp90-ELISA) was developed. After optimization, the optimal conditions were as follows: coating antigen concentration of 4 µg/mL with overnight incubation at 4 °C; blocking with 5% skim milk at 37 °C for 1.5 h; serum dilution of 1:200 with incubation at 37 °C for 45 min; secondary antibody dilution of 1:1000 with incubation at 37 °C for 30 min; and color development using TMB substrate at room temperature in the dark for 10 min. The cut-off value was defined as an OD₄₅₀ ≥ 0.22 for positive samples and <0.22 for negative samples. The developed gp90-ELISA specifically detected REV-positive sera at a maximum serum dilution ratio of 1:3200. Intra- and inter-assay variation coefficients were ≤10%, indicating that the gp90-ELISA had good specificity, sensitivity, and reproducibility. Laboratory serum testing showed that the gp90-ELISA successfully detected sera from chickens immunized with the gp90 protein or infected with REV. Furthermore, analysis of clinical serum samples demonstrated 100% concordance between the gp90-ELISA results and a commercial whole-virus-coated ELISA kit. These results indicate that the gp90-ELISA is a reliable supplementary method to whole-virus-coated ELISA and has potential utility in disease surveillance and evaluation of immune responses. Full article

Background: Urine cytology remains widely used for surveillance of non-muscle-invasive bladder cancer despite well-known limitations in sensitivity, especially for low-grade tumors. Uromonitor^®, a molecular assay detecting TERT promoter, FGFR3, and KRAS mutations in voided urine, has emerged as a promising adjunct. To evaluate its suitability for routine use, a consolidated assessment of diagnostic performance and a direct comparison with urine cytology are needed. Methods: We conducted a prospectively registered systematic review (PROSPERO CRD420251173244), synthesizing all available studies that evaluated Uromonitor^® for the detection of urothelial carcinoma of the bladder (UCB). Methodological quality was assessed using the QUADAS-2 framework, and certainty of evidence was evaluated following GRADE for diagnostic tests. Sensitivity was prespecified as the primary endpoint. Comparative datasets were identified, and random-effects meta-analyses were performed for sensitivity, specificity, accuracy, and predictive values (PVs). Results: Across eight cohorts evaluating Uromonitor^®, 832 of 3196 patients (26.0%) had histologically confirmed UCB. Aggregated sensitivity was 0.55 (95% CI 0.52–0.58). Specificity was 0.95 (0.94–0.96). Accuracy was 0.85 (0.83–0.86). PPV was 0.79 (0.76–0.82), and NPV was 0.86 (0.84–0.87). Across seven paired datasets, urine cytology demonstrated a sensitivity of 0.42, a specificity of 0.91, an accuracy of 0.78, a PPV of 0.64, and an NPV of 0.81. Pooled odds ratio for sensitivity was 3.16 (0.73–13.76), while diagnostic accuracy yielded 1.71 (1.01–2.90). Differences in specificity and NPV were not statistically significant, whereas the PPV favored Uromonitor^®, reaching statistical significance in pooled analyses. Conclusions: Uromonitor^® demonstrates higher sensitivity and improved accuracy compared with urine cytology, although current performance remains insufficient for stand-alone surveillance. The sensitivity estimate showed very low certainty due to pronounced heterogeneity, underscoring the need for careful interpretation. With advancing DNA recovery methods, incorporation of droplet digital PCR, and rigorous evaluations in prospective multicenter studies, Uromonitor^® may become an integral element of risk-adapted follow-up strategies. Full article

Background: Lung carcinoids—typical and atypical—are rare neuroendocrine tumors (NETs) representing 1–2% of lung cancers. Despite clinicopathological differences, their clinical management often mirrors lung cancer protocols rather than NET-specific recommendations. Objectives: Portray a 12-year real-world experience with lung carcinoids at a Comprehensive Cancer Center, identifying gaps in diagnostic work-up, treatment decision-making, and follow-up. Methods: Retrospective observational cohort study of adult patients with histologically confirmed lung carcinoids diagnosed at IPO Porto between January 2013 and December 2024. Demographic, clinical, imaging, and treatment data were collected from electronic patient records. Analyses were descriptive. Results: Among 179 identified cases, 129 met eligibility criteria. Median age was 62 years (range 18–84); 53.6% were women and 53.5% were non-smokers; 84.5% had ECOG-PS 0–1. The most frequent presentation was respiratory symptoms (34.1%), followed by incidental findings (43.4%, of which ~20% were during staging or surveillance of other cancers). Typical carcinoids accounted for 49.6% and atypical for 43.4%. FDG-PET/CT was requested in 70.9% of cases, including many with typical carcinoid, and SSTR-PET/CT in 64.6% (dual PET in 38.8%). Most patients (65.1%) presented with stage I disease; 17.1% were stage IV. Mean time-to-first treatment was 83 days (range 1–259). Surgery was the first treatment option for 78.3% of patients. Conclusions: This real-world series highlights heterogeneity in diagnostic pathways, excessive FDG-PET use in typical carcinoids, and non-standardized follow-up. Dedicated multidisciplinary lung-NET boards and national reference centers are needed to homogenize and streamline patient management. Full article

Background/Objectives: Non-muscle invasive bladder cancer (NMIBC) management is increasingly complex due to conflicting guideline-based risk classifications, ongoing Bacillus Calmette–Guérin (BCG) shortages, and emerging alternative therapies. Computational Histology Artificial Intelligence (CHAI) tests are clinically available, providing insights from tumor specimens including predicting BCG responsiveness and individualized recurrence and progression risks, which may support precision medicine. This technology features biomarkers purpose-built for clinically unmet needs and has practical advantages including a fast turnaround time and no need for consumption of tissue or other specimens. We assessed the impact of such tests on physicians’ decision-making in routine, real-world NMIBC management. Methods: Physicians at six centers ordered CHAI tests (Vesta Bladder) at their discretion during routine NMIBC care. Tumor specimens were processed by a CLIA/CAP-accredited laboratory (Valar Labs, Houston, TX, USA) where H&E-stained slides were analyzed with the CHAI assay to extract histomorphic features of the tumor and microenvironment, which were algorithmically assessed to generate biomarker test results. For each case from 24 June 2024 to 18 July 2025, ordering physicians were surveyed to assess pre- and post-test management plans and post-test result usefulness. Results: Among 105 high-grade NMIBC cases with complete survey results available, primary management changed in 67% (70/105). Changes included modality shifts (n = 7; three to radical cystectomy with high prognostic risk scores; four avoiding cystectomy with low scores) and intravesical agent change (n = 63). Surveillance was intensified in 7%, predominantly among those with ≥90th percentile risk scores. The therapeutic agent changed in 80% (40/50) of predictive biomarker-present (indicative of poor response to BCG) tumors vs. 48% (23/48) of biomarker-absent tumors. Conclusions: In two thirds of cases, CHAI biomarker results influenced clinical decision-making during routine care. BCG predictive biomarker results frequently guided intravesical agent selection. These results have implications for optimizing clinical outcomes, especially in the setting of ongoing BCG shortages. Prognostic risk stratification results guided treatment escalation vs. de-escalation, including surveillance intensification and surgical vs. bladder-sparing decisions. CHAI biomarkers are currently utilized in routine clinical care and informing precision NMIBC management. Full article

Liquid biopsy is moving beyond mutation-centric assays to multimodal frameworks that integrate cell-free DNA (cfDNA) signals with additional analytes such as circulating tumor cells (CTCs) and extracellular vesicles (EVs). In this review, we summarize emerging technologies across analytes for early cancer detection, emphasizing sequencing and error-suppression strategies and the growing evidence for multi-cancer early detection (MCED), tissue-of-origin (TOO) inference, diagnostic triage, and longitudinal surveillance. At low tumor fractions, fragmentomic and methylation features preserve tissue and chromatin context; when combined with radiomics using deep learning, they support blood-first, high-specificity risk stratification, increase positive predictive value (PPV), reduce unnecessary procedures, and enhance early prediction of treatment response and relapse. Building on these findings, we propose a pathway-aware workflow: initial blood-based risk scoring, followed by organ-directed imaging, and targeted secondary testing when indicated. We further recommend that model reports include not only discrimination metrics but also calibration, decision-curve analysis, PPV/negative predictive value (NPV) at fixed specificity, and TOO accuracy, alongside multi-site external validation and blinded dataset splits to improve generalizability. Overall, liquid biopsy is transitioning from signal discovery to deployable multimodal decision systems; standardized pre-analytical and analytical workflows, robust error suppression, and prospective real-world evaluations will be pivotal for clinical implementation. Full article

Nucleoside analogs remain central to the treatment of hematologic malignancies and solid tumors, yet resistance frequently occurs, contributing to relapse and disease-related mortality. Rather than arising from a single mechanism, effective nucleoside analog activity requires successful navigation of multiple biological barriers, including cellular uptake, intracellular activation, nucleotide pool balance, genome surveillance, and mitochondrial stress responses. This review integrates recent advances describing how alterations at each of these levels contribute to resistance to nucleoside analog therapies. We further highlight emerging therapeutic strategies centered on small-molecule inhibitors that exploit these vulnerabilities to enhance the efficacy of nucleoside analogs. Together, this integrative perspective supports the need for development of small molecule inhibitors and design of combination approaches aimed at restoring apoptotic competence and improving the use of nucleoside analog-based therapies for the treatment of cancer. Full article

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article

Background and Clinical Significance: Percutaneous ablation is an increasingly used nephron-sparing treatment for small renal masses (SRMs). Although generally considered safe, tumor seeding along the applicator tract is rare (<0.1%) and may be underreported. This study reviews the existing literature to synthesize patterns, potential risk factors, and clinical presentation of this complication following percutaneous thermal ablation of renal cell carcinoma (RCC). Case Presentation: We report the case of an 84-year-old man who developed late subcutaneous abdominal-wall tumor seeding more than ten years after nephron-sparing surgery for a T1a renal mass and following three sessions of percutaneous cryo- and microwave ablation for recurrent clear-cell renal cell carcinoma (ccRCC). The lesion was surgically excised, and histology confirmed ccRCC with negative margins. A descriptive literature review was conducted using PubMed and ScienceDirect to identify English-language case reports and case series (CS) documenting tumor seeding after RCC percutaneous ablation. Eight studies involving nine patients met the inclusion criteria. The median age was 66 years (interquartile range [IQR] 64–74; range 47–84). The median follow-up duration was 11 months (IQR, 4.5–18.5; range 3–60), and the median interval to tumor seeding was 11 months (IQR, 6–18.5; range 3–60). Management included surgical excision (50%), repeat cryoablation (25%), and systemic therapy or supportive care (25%). Conclusions: Tumor tract seeding following percutaneous ablation for RCC is rare, with variable latency and presentation. Procedural factors such as the absence of tract ablation, multiple probe passes, and intra-procedural biopsy may increase risk. Awareness of this complication and long-term surveillance should be incorporated into follow-up protocols. Despite this risk, percutaneous ablation remains a safe and effective option for appropriately selected patients. Full article

Introduction: In rectal cancer, the choice of treatment strategy depends on the tumor stage and the response to neoadjuvant therapy. Accurate assessment of tumor regression through magnetic resonance imaging (MRI) may help to guide personalized approaches, including delayed or nonoperative management. This study aimed to assess the correlations between pathological complete response (pCR) and clinical staging before and after neoadjuvant treatment in rectal cancer patients. Methods: We conducted a retrospective analysis of rectal cancer patients treated with neoadjuvant therapy followed by radical resection in our oncological surgery department between July 2012 and December 2024. Clinical staging and tumor response were assessed using MRI, focusing on T- and N-stage evaluation. Pathological complete response (pCR) was defined as the absence of tumor cells on histopathological examination. Associations between pCR and clinical variables were explored. Results: Out of a total of 1693 rectal cancer patients, 783 (46.25%) received neoadjuvant therapy, with 62 patients (7.92%) presenting pCR. The majority had tumor stage cT3 (n = 45, 72.6%) and lymph node stage cN2b (n = 25, 40.3%) before treatment. Post-treatment MRI showed complete tumor response (T0) in 20 patients (32.3%) and nodal downstaging to N0 in 34 patients (54.8%). MRI provided imaging findings that indicate a limited correlation between clinical assessment of tumor response and pathological outcome. Six patients (9.6%) developed distant metastases, and there were no local recurrences. Conclusions: While MRI provides valuable preoperative information, its accuracy in predicting pCR remains limited. Achieving pCR is a favorable prognostic indicator, but it does not eliminate the risk of distant metastasis; therefore, continued surveillance and individualized management strategies remain essential to optimize outcomes in rectal cancer patients. Full article

Background: In malignant pleural mesothelioma, epithelioid histology is traditionally considered a favorable prognostic marker. However, it remains clinically undetermined whether the intensity of an oncogenic insult can disrupt this link. Radiation-induced cases serve as an unconfounded biological model to dissect such trajectories masked by asbestos confounding. Methods: We performed an Individual Patient Data (IPD) synthesis of 20 strictly asbestos-unexposed human cases, applying clinically established dose stratification (intermediate: 20–45 Gy vs. high: >45 Gy). To confirm the observed pattern, we examined data from 829 dogs in the Colorado State University (CSU) Beagle Study. Results: In the intermediate-dose group (n = 13), a significant positive correlation persisted between age at radiotherapy and the latent period (ρ = 0.567, p = 0.043). Conversely, high-dose exposure (>45 Gy) showed a disruption of this age-dependent pattern, with a trend toward inverse correlation (ρ = −0.754, p = 0.084). Interaction analysis confirmed a statistically significant divergence between these dose-dependent trends (p = 0.005). The CSU Beagle Study (n = 829) demonstrated the physical basis of this phenomenon: in the canine model, high-dose exposure (≥0.74 Gy) triggered a “Step-Jump” in cumulative incidence (30.4% at 0.5 years), indicating instantaneous carcinogenic onset distinct from cumulative biological aging. Conclusions: This kinetic divergence points to a “Diagnostic Trap.” We propose a ‘Single- to Double-Brake’ framework where intermediate doses preserve age-dependent progression, whereas high doses likely trigger catastrophic genomic failure (chromothripsis) that bypasses the time required for morphological dedifferentiation. Consequently, morphologically indolent epithelioid tumors in high-dose survivors may harbor aggressive molecular profiles not predicted by histology alone, necessitating risk-stratified precision surveillance. Full article

Background: Parotid gland tumors pose diagnostic and surgical challenges due to their histological heterogeneity and proximity to the facial nerve. This study aimed to evaluate clinicopathological features and postoperative outcomes with a specific focus on facial nerve function in patients undergoing parotidectomy. Methods: This retrospective study included 314 patients who underwent parotidectomy between 2008 and 2024 at a tertiary center. Demographic data, tumor histology, and postoperative complications—particularly facial nerve paralysis within the first three months—were analyzed. Histopathological features including capsular, perineural, and lymphovascular invasion were also assessed. Results: Of all cases, 79% were benign, 14.6% malignant, and 6.4% non-neoplastic. Pleomorphic adenoma and Warthin tumor were the most common benign entities, while mucoepidermoid carcinoma was the most frequent malignancy. Malignant tumors were associated with higher rates of positive surgical margins (44.2% vs. 12.5%, p < 0.001), capsular invasion (25% vs. 7%, p < 0.001), and tumor necrosis (22% vs. <1%, p < 0.001). Facial paralysis occurred in 4.4% of patients, largely transient and significantly associated with malignant tumors (p < 0.001) and extensive lymph node dissection (p < 0.001). Capsular invasion and necrosis were rare in benign lesions but still observed, especially in pleomorphic adenoma. Conclusions: Histopathologic aggressiveness markers were associated with malignant disease and postoperative facial nerve dysfunction. These findings support a risk-stratified approach to follow-up: all patients undergo universal early assessment at two weeks and three months, after which surveillance intensity may be individualized according to histopathologic features—such as necrosis, perineural invasion, capsular invasion, or positive margins. Full article

Background: Site-specific long-term outcomes, including neurofibromatosis type 1 (NF1), Ki-67 prognostic value, and very late recurrences of small bowel gastrointestinal stromal tumors (GISTs), remain inadequately defined. Methods: This retrospective cohort study investigated the clinical characteristics, diagnostic challenges, and long-term outcomes of patients with small bowel GISTs. This retrospective, single-center study (2008–2024) analyzed 27 consecutive patients (average age: 62.2 years) with jejunal/ileal GISTs. Clinicopathologic features, diagnostic yield of balloon-assisted enteroscopy (BAE), treatments, and outcomes were evaluated during a 10.2-year median follow-up period. Recurrence-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier with log-rank testing. Ki-67 was assessed using MIB-1; a prespecified 5% cut-off was chosen based on prior evidence. Results: Tumor (mean size, 62.4 mm) sites included the jejunum (74.1%) and ileum (25.9%). NF1 was present in 3/27 (11.1%) patients, all with multiple jejunal tumors. Among the 14 patients who underwent BAE, biopsy was attempted in six and yielded a histological diagnosis in one (16.7%). Six patients had recurrence; two died from disease >10 years postoperatively. Five-year OS and RFS were 91.3% and 68.7%, respectively. Adverse RFS was associated with ileal location (p = 0.03), size ≥ 10 cm (p < 0.001), mitoses > 5/50 high-power fields (p = 0.002), and Ki-67 ≥ 5% (p < 0.001). One patient labeled low risk by conventional models had recurrence with Ki-67 = 10%. Another classified as low risk by conventional models experienced recurrence >10 years after surgery, with a Ki-67 index of 10%. Conclusions: Extended, risk-adapted surveillance may be reasonable for small-bowel GISTs, and it may be beneficial to incorporate Ki-67 (≥5%) into site-based risk stratification. These observations remain hypothesis-generating and require validation in larger, multicenter cohorts and prospective studies. Full article