Search Results (283)

Background: Small-bowel cancers (SBCs) are rare, histologically diverse malignancies with limited data from Asian populations. This study aimed to describe histological subtype distribution, clinical features, survival outcomes, and prognostic factors in SBCs over a 20-year period. Methods: We retrospectively reviewed patients diagnosed with SBC at a tertiary referral center in Southern Thailand (2005–2024). Clinical, pathological, and radiological data were analyzed by histologic subtype. Results: A total of 158 patients were included: adenocarcinoma (81.0%), gastrointestinal stromal tumor (GIST, 5.7%), well-differentiated neuroendocrine tumor (NET, 5.7%), other sarcomas (5.1%), and poorly differentiated neuroendocrine carcinoma (NEC, 2.5%). Adenocarcinoma predominantly affected older patients and frequently presented with advanced-stage disease and poor performance status, whereas NET and NEC occurred in younger patients typically at early NET and metastatic NEC stages. Median overall survival (OS) varied by subtype: adenocarcinoma (8.3 months), GIST (63.6 months), NEC (8.9 months), NET (not reached), and other sarcomas (9.8 months). Five-year OS rates were 14.0%, 55.6%, 0%, 88.9%, and 18.8%, respectively. Eastern Cooperative Oncology Group performance status ≥2, duodenal location, and metastatic disease were independently associated with worse OS. Conclusions: SBCs display distinct clinical and prognostic profiles by subtype. Overall prognosis remained poor, underscoring the need for earlier detection and subtype-specific management. Full article

Background: Non-islet cell tumor hypoglycemia is increasingly reported with gastrointestinal stromal tumors (GIST), but population-level estimates of its clinical impact are limited. We evaluated associations between hypoglycemia and inpatient outcomes among GIST hospitalizations. Methods: We conducted a retrospective cross-sectional study of the National Inpatient Sample (NIS) 2018–2020. Adult GIST discharges were identified by ICD-10-CM codes and stratified by hypoglycemia. Primary outcomes were in-hospital mortality and resource utilization—length of stay (LOS) and total hospital charge. Secondary outcomes included malnutrition, sepsis, ascites, peritonitis, bowel perforation, intestinal obstruction, gastrointestinal bleeding, and iron deficiency anemia. Analyses used survey-weighted logistic regression for binary outcomes and generalized linear models for continuous outcomes. A propensity score-matched sensitivity analysis balanced sepsis and malnutrition. Results: Among 61,725 GIST hospitalizations, 0.72% had hypoglycemia. Mortality was 12.6% with hypoglycemia vs. 3.1% without; adjusted odds of death were higher (aOR 4.16, 95% CI 2.06–8.37; p < 0.001). Hypoglycemia was also associated with malnutrition (aOR 5.63, 3.37–9.40), sepsis (aOR 4.00, 2.24–7.14), ascites (aOR 3.43, 1.63–7.19), and peritonitis (aOR 2.91, 1.17–7.22). LOS was 4.61 days longer on average (not significant; p = 0.185), and total hospital charge was $5218 higher (β = 19,116.8; p = 0.95). In the matched cohort, the mortality association attenuated but persisted (aOR 1.38, 1.27–1.49; p < 0.001); peritonitis remained significant (aOR 1.10, 1.04–1.17), intestinal obstruction (aOR 4.91, 3.44–7.05) and iron deficiency anemia (aOR 3.54, 1.62–7.74) became significant, while ascites and gastrointestinal bleeding were not significant. Conclusions: Hypoglycemia in GIST, although uncommon, marks a higher-risk inpatient trajectory with increased mortality and several complications; these signals largely persist after balancing severity proxies. Resource-use differences were directionally higher but not statistically significant. Recognition of hypoglycemia may aid risk stratification and inpatient management in GIST. Full article

Face recognition technology utilizes unique facial features to analyze and compare individuals for identification and verification purposes. This technology is crucial for several reasons, such as improving security and authentication, effectively verifying identities, providing personalized user experiences, and automating various operations, including attendance monitoring, access management, and law enforcement activities. In this paper, comprehensive evaluations are conducted using different face detection and modality segmentation methods, feature extraction methods, and classifiers to improve system performance. As for face detection, four methods are proposed: OpenCV’s Haar Cascade classifier, Dlib’s HOG + SVM frontal face detector, Dlib’s CNN face detector, and Mediapipe’s face detector. Additionally, two types of feature extraction techniques are proposed: hand-crafted features (traditional methods: global local features) and deep learning features. Three global features were extracted, Scale-Invariant Feature Transform (SIFT), Speeded Robust Features (SURF), and Global Image Structure (GIST). Likewise, the following local feature methods are utilized: Local Binary Pattern (LBP), Weber local descriptor (WLD), and Histogram of Oriented Gradients (HOG). On the other hand, the deep learning-based features fall into two categories: convolutional neural networks (CNNs), including VGG16, VGG19, and VGG-Face, and Siamese neural networks (SNNs), which generate face embeddings. For classification, three methods are employed: Support Vector Machine (SVM), a one-class SVM variant, and Multilayer Perceptron (MLP). The system is evaluated on three datasets: in-house, Labelled Faces in the Wild (LFW), and the Pins dataset (sourced from Pinterest) providing comprehensive benchmark comparisons for facial recognition research. The best performance accuracy for the proposed ten-feature extraction methods applied to the in-house database in the context of the facial recognition task achieved 99.8% accuracy by using the VGG16 model combined with the SVM classifier. Full article

Gastric subepithelial tumors (SETs) are commonly identified during routine endoscopy. Most SETs are asymptomatic and small (<2 cm) and exhibit benign behavior over time. Various histopathological types exist, including benign lesions, such as lipomas and heterotopic pancreas, and malignant lesions, such as gastrointestinal stromal tumors (GISTs). Endoscopic ultrasound (EUS) plays a critical role in evaluating the lesion size, layer of origin, border characteristics, and internal echogenicity. Approximately 4–15% of gastric SETs increase in size over ~5 years. The risk factors for the growth and malignant potential of SETs include initial tumor size, irregular or heterogeneous EUS features, mucosal ulceration, and confirmed GIST diagnosis. While lesions ≥2 cm in size or those with high-risk features are typically subjected to resection, small and low-risk SETs are managed with periodic EUS or endoscopic surveillance. Tissue acquisition via EUS-guided biopsy or endoscopic resection is warranted for indeterminate or suspicious cases. A risk-stratified approach minimizes unnecessary interventions while enabling timely detection of clinically significant lesions. Surveillance protocols should be tailored according to characteristics of SETs, patient comorbidities, and diagnostic confidence. This review highlights the long-term outcomes of gastric SETs, evaluates established risk factors for their growth and malignant potential, and discusses evidence-based strategies for surveillance and management. Full article

Background/Objectives: Computed tomography (CT)-based radiomic analysis is an emerging technique that enables non-invasive assessment of tumor characteristics. In gastrointestinal stromal tumors (GISTs), radiomics may reflect biological behavior such as proliferative activity, often indicated by Ki-67 expression. To our knowledge, this is the first systematic review and meta-analysis synthesizing evidence on the ability of CT radiomics to predict the Ki-67 index in GISTs, addressing an important gap in the literature. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the predictive performance of CT radiomics for Ki-67 expression in GISTs. A literature search of PubMed, Scopus, Science Direct, and the Cochrane Library was performed up to December 2024 using predefined terms. Extracted data included study design, patient demographics, imaging protocols, radiomic features, and diagnostic performance. Study quality was assessed using the QUADAS-2 tool. A random-effects meta-analysis summarized the pooled area under the ROC curve (AUC), sensitivity, and specificity. Subgroup and sensitivity analyses explored heterogeneity sources. Publication bias was assessed using Egger’s test and funnel plots. Results: Six studies involving 1632 patients were included. The pooled sensitivity and specificity for predicting Ki-67 expression were 0.71 and 0.76, respectively, with a summary AUC of 0.79. Subgroup analyses showed consistent results across different imaging protocols and radiomic feature sets, though the Ki-67 cutoff (8% vs. 10%) affected diagnostic performance. Moderate heterogeneity and potential publication bias in specificity were observed. Conclusions: CT-based radiomics demonstrates moderate accuracy for non-invasively predicting Ki-67 index in GISTs. While not a substitute for histology, it may support personalized preoperative planning and guide future immunotherapy strategies. In the future, radiomic signatures—particularly when integrated with molecular or immune-related biomarkers—could help refine patient selection and monitoring strategies for emerging therapies, including immunotherapy. Full article

We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary KIT mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, a knockdown of CLDN1 or inhibition of its activity by PDS-0330 effectively restored GIST’s sensitivity to IM both in vitro and in vivo. This was evidenced by the increased expression of apoptotic markers (e.g., cleaved PARP and caspase-3) and the decreased proliferation rate of IM-resistant GIST T-1R cells treated with a combination of IM and PDS-0330 (or siRNA CLDN1). In concordance with these findings, a significant synergy was observed between IM and PDS-0330 in GIST T-1R cells. Importantly, decreased tumor size and weight were observed in IM-resistant GIST xenografts treated with a combination of IM and PDS-0330. Furthermore, the combined treatment of IM-resistant tumors induced an increase in intratumoral apoptosis and other changes, as defined by the histopathologic response rate. Based on the co-immunoprecipitation and immunofluorescence microscopy data, we also demonstrated the strong interaction pattern between CLDN1 and FGFR2. Of note, the inhibition or knockdown of CLDN1 effectively decreased the phosphorylation of FGFR2 and FRS-2, a well-known FGFR adaptor protein, thereby illustrating CLDN1’s ability to regulate FGFR-signaling and thereby promote FGFR-mediated survival in KIT-inhibited GIST. Consequently, CLDN1 inhibition in GIST effectively disrupted the FGFR-mediated pathway and re-sensitized tumor cells to IM. In concordance with these data, molecular profiling of CLDN1-inhibited GIST T-1R cells illustrated a significant decrease in the majority of FGFR transcripts, including FGFR2, 3, and 4. Additionally, several FGFR ligands (e.g., FGF14, -19, and -23) were also down-regulated in PDS-0330-treated GIST. Notably, exogenous FGF-2 increased CLDN1 expression in a time-dependent manner. In contrast, pan-FGFR inhibitors effectively reduced CLDN1 levels in IM-resistant GIST T-1R cells, thereby illustrating a cross-talk between CLDN1- and FGFR-mediated pathways in IM-resistant GIST. Based on subcellular fractionation and immunofluorescence microscopy data, we also observed partial relocalization of CLDN1 into the cytoplasm in IM-resistant GIST. Notably, PDS-0330 effectively abrogated this relocalization, suggesting that changes in CLDN1 subcellular distribution might also impact GIST resistance to IM. Lastly, based on our small cohort clinical study (n = 24), we observed the increased expression of CLDN1 in most “high-risk” primary GIST known to be associated with poor prognosis and aggressive behavior, thereby illustrating the prognostic value of increased CLDN1 expression in GIST and providing a further rationale to evaluate the effectiveness of CLDN1 inhibition for GIST therapy. Full article

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors primarily located in the stomach and small intestine; their occurrence in the terminal ileum is particularly rare. Although GISTs can develop throughout the gastrointestinal tract, cases of perforation in elderly individuals are even less common, posing significant diagnostic and therapeutic challenges. This case report describes an 86-year-old male patient with an acute abdomen caused by a terminal ileum perforated GIST requiring urgent surgical intervention. An immunohistochemical examination of the tumor confirmed a GIST with a GILT (gastrointestinal leiomyogenic tumor) immunophenotype. The rarity of this condition makes it diagnostically challenging, as its symptoms are often nonspecific, and GISTs are frequently overlooked, particularly in older patients. This case supplements the existing literature by emphasizing the importance of considering GIST perforation in the differential diagnosis of an acute abdomen, even in elderly patients and in rare anatomical locations. Full article

This case represents a relatively rare localization of a gastrointestinal stromal tumor involving the distal esophagus with a very unusual mode of metastatic spread to the lymph nodes and bone structures. Diagnostic follow-up showed the effect of tyrosine kinase inhibitor therapy on metastatic lesions, highlighting the necessity of comprehensive diagnostic evaluation in patients with atypical presentations and contributing to the improvement of therapeutic strategies in complex clinical scenarios. Full article

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by activating mutations in KIT (CD117) and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors (TKIs), especially imatinib, has significantly transformed GIST treatment. However, the emergence of both primary and secondary resistance to imatinib presents ongoing therapeutic challenges. This review comprehensively explores the mechanisms underlying imatinib resistance and evaluates subsequent TKI therapies. Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents—such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib—have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs. Despite progress, long-term efficacy remains limited due to evolving resistance. Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options, especially for rare GIST subtypes. Full article

Rare presentations are surprising and may disturb the day-to-day routine of a medical unit; however, they are expected (not as individual entities, but as a group of “uncommon causes”). While reviewing the literature in relation to three clinical cases of upper gastrointestinal bleeding (UGIB) encountered in our institution—gastric metastases of breast cancer (GMB), pyloric gland adenoma, and gastrointestinal stromal tumor (GIST)—we identified seven and 29 case reports for the first two entities, and over 100 publications addressing GIST. This prompted a shift in focus from novel reporting to diagnostic contextualization. We found it difficult to obtain an overview of the spectrum of UGIB etiologies, as most publications refer to a few individual entities or to a subgroup of rare causes. The narrative review we conducted arose from this particular research methodology. Based on a broad literature search, UGIB etiologies were organized in five categories (lesions of the mucosa, neoplasms, vascular causes, bleeding predisposition, and external sources of bleeding). In the management of patients with UGIB, the underlying etiology deviates from the classic peptic ulcer disease/esophageal varices dyad in approximately half of the cases. This underscores the need for heightened clinical vigilance, particularly in complex scenarios, where endoscopic findings, imaging results, and histopathological interpretations may be unexpected or prone to misinterpretation. As an illustration, we conducted two systematic reviews of case reports of bleeding GMB and PGA. Our findings support a proactive diagnostic and research mindset and advocate for improved awareness of uncommon UGIB etiologies. Full article

(1) Background: Quality of life (QoL) assessment is a crucial aspect for patients diagnosed with cancer. Over the years, different tools have been developed to measure QoL, both generic and pathology specific, but the inclusion of quality of life among other indicators of efficacy in randomized controlled trials (RCTs) remains a controversial issue. In this review, we aim to review the frequency and modality of QoL assessment in RCTs, enrolling patients diagnosed with mesenchymal tumors. (2) Methods: An electronic literature search of bone and soft tissue sarcoma and GIST-related RCTs published between January 2000 and December 2023 was performed by two independent reviewers using PubMed. English-language phase II and III clinical trials enrolling at least more than 15 patients were included, regardless of the disease stage. Studies involving patients under the age of 18 years or for which the full text was not available were excluded. For each study, data regarding the journal and year of publication, the study design, the primary objective, and the evaluation of quality of life as an endpoint with any type of patient-reported outcomes used were extracted. (3) Results: Among the 742 publications screened, 171 resulted eligible. QoL assessment was listed among the endpoints in 35 trials and QoL results were reported in 29 primary publications. In these trials, 16 included patients with soft tissue sarcomas, 8 Kaposi sarcomas, 6 GIST, and 3 desmoid tumors. Among all the trials included, 10.4% on an adjuvant/neoadjuvant setting and 24.4% on a metastatic setting included QoL as an endpoint. The proportion of trials, including QoL, was variable over time, as follows: 16.9% of trials in 2000–2014 vs. 23.4% in 2015–2023. In 35 trials, including QoL endpoints, 27 had a superiority design and 25 reported a positive result. In the majority of trials (80%), the tools for QoL assessment were generic and those mostly used were the EORTC QLQ-C30, the EQ-5D questionnaire, and the modified Brief Pain Inventory–Short Form. (4) Conclusions: Quality of life has not been assessed or published in many phase II and III trials, despite an improvement over time. QoL evaluation in RCTs should be considered even more carefully in patients with rare tumors, where the low number of patients who can be enrolled makes it difficult to draw statistically significant conclusions on the effectiveness of treatments. Full article

Primary hepatic gastrointestinal stromal tumours (PHGISTs) are rare and frequently misdiagnosed due to their atypical presentation and uncertain origin. The purpose of this article is to present the case of a 79-year-old female patient with a gigantic PHGIST characterized by a predominantly cystic nature—an extremely rare presentation, as most cases of PHGIST are solid. Despite extensive imaging and exploratory laparotomy, the primary origin remained uncertain, leading to questioning about whether it was a true primary hepatic GIST or an atypical metastatic lesion. The initial therapeutic approach involved a surgical procedure aimed to confirm the diagnosis and achieve reductive tumourectomy. Following the surgery, the patient was administered imatinib with a favourable clinical response for four and a half years—an atypical pattern of resistance, as most patients typically develop therapeutic resistance within two to three years. A second surgical intervention was performed to address a cystic lesion localized in the left hepatic lobe, followed by an atypical segment III hepatectomy to achieve macroscopic resection. Subsequently, the patient received sunitinib for two and a half years, which resulted in temporary disease stabilization. However, the sunitinib treatment was associated with hypertension and leukopenia. The patient’s overall survival was 8 years, suggesting that individualized therapeutic strategies and close monitoring might be the key in such cases. Furthermore, this case confirms the role of surgical intervention even in advanced disease stages, with multiple major resections contributing significantly to prolonged survival. The interplay between surgical and oncologic therapies remains essential to guiding clinical decisions. Given the unusual cystic presentation, this case highlights the necessity to expand the pathological and molecular profiling of PHGISTs. Furthermore, the atypical timeline of resistance development and treatment-related toxicity emphasizes the importance of further research into the genetic and pharmacological determinants of PHGISTs. These findings advocate for the refinement of diagnostic, therapeutic, and surveillance protocols tailored to rare GIST subtypes. Full article

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma, characterized by a COL1A1-PDGFB fusion. Imatinib, a multi-target tyrosine kinase inhibitor, is a standard treatment of DFSP. However, resistance emerges in 10–50% of cases. There is an urgent need for predictive biomarkers to refine the patient selection and improve therapeutic outcomes. We aimed to identify predictive biomarkers for imatinib response and explored a pharmacokinomic approach using in vitro assays with patient-derived DFSP cell lines. Four DFSP cell lines that we established were analyzed for tyrosine kinase activities on PamChip, a three-dimensional peptide array, in the presence and absence of imatinib, along with an imatinib-sensitive cell line, GIST-T1, as a positive control. Drug screening was also performed using 60 FDA-approved tyrosine kinase inhibitors, including imatinib. The kinomic profiles were compared with the kinase inhibitor screening results to identify predictive druggable targets. Drug sensitivity was associated with increased activity of PDGFRB, as indicated by the PamChip assay and Western blotting. Furthermore, imatinib sensitivity correlated with the activity of three kinases: FER, ITK, and VEGFR1, suggesting their potential as potential predictive biomarkers. Our cell-based pharmacokinomic approach using patient-derived DFSP cell lines would facilitate the identification of resistant cases to imatinib and guide alternative therapeutic strategies. Full article

Background/Objectives: The present investigation quantifies the striking predisposition for small intestinal GISTs in NF-1 patients, examining both multifocal and solitary tumor patterns while establishing critical epidemiological comparisons with the general population. By elucidating these distinct clinical and biological profiles, the study aims to transform the understanding of NF1-associated tumorigenesis and optimize patient surveillance strategies. Methods: This systematic review and meta-analysis was conducted in strict accordance with PRISMA guidelines, the gold-standard framework for minimizing bias and maximizing reproducibility in evidence synthesis. Prospectively registered in PROSPERO, the study employed a PICO framework to evaluate interventions, outcomes, and comparisons. Results: This systematic review and meta-analysis reveals a profound oncogenic propensity for small intestinal GISTs in NF-1 patients, demonstrating markedly increased prevalence relative to population baselines. The tumors display characteristic presentation and histological profiles, with a distribution of 54% multifocal lesions, 41% solitary SI-GIST, and 5% solitary duodenal GIST cases, demonstrating the diverse clinical manifestations of NF-1-associated tumors. These compelling findings not only redefine the epidemiological landscape of NF1-associated malignancies but also underscore extraordinary disease susceptibility, far surpassing previous estimates and sporadic occurrence rates in the general population. Conclusions: The distinct clinical patterns and high frequency of these tumors among NF-1 patients provide important insights into GIST development while underscoring the need for heightened clinical suspicion, particularly in patients manifesting gastrointestinal hemorrhage. These findings highlight the unique challenges in managing these cases—including diagnostic limitations and therapeutic constraints—underscoring the imperative for multidisciplinary therapeutic frameworks for detection, monitoring and treatment in this high-risk population. Full article

This paper provides a conceptual framework for soundscape appraisal as a key outcome of the hearing process. Sound appraisal involves auditory sense-making and produces the soundscape as the perceived and understood acoustic environment. The soundscape exists in the experiential domain and involves meaning-giving. Soundscape research has reached a consensus about the relevance of two experiential dimensions—pleasure and eventfulness—which give rise to four appraisal quadrants: calm, lively/vibrant, chaotic, and boring/monotonous. Requirements for and constraints on the hearing and appraisal processes follow from the demands of living in a complex world, the specific properties of source and transmission physics, and the need for auditory events and streams of single-source information. These lead to several core features and functions of the hearing process, such as prioritizing the auditory channel (loudness), forming auditory streams (audibility, primitive auditory scene analysis), prioritizing auditory streams (audible safety, noise sensitivity), and initial meaning-giving (auditory gist and perceptual layers). Combined, this leads to a model of soundscape appraisal yielding the ISO quadrant structure. Long-term aggregated appraisals lead to a sonic climate that allows for an insightful comparison of different locations. The resulting system needs additional validation and optimization to comply in detail with human appraisal and evaluation. Full article