Search Results (691)

Objective: We aimed to investigate whether ultrasound-based texture analysis can differentiate liver metastases according to the histopathological origin of the primary tumor and to evaluate the quantitative texture characteristics of metastases originating from colorectal, pancreatic, and breast cancer. Materials and Methods: This prospective study included 75 patients with biopsy-proven liver metastases, comprising 25 colorectal adenocarcinoma, 25 pancreatic ductal adenocarcinoma, and 25 invasive ductal breast carcinoma metastases. Conventional B-mode ultrasound images were obtained prior to treatment. The largest metastatic lesion in each patient was manually segmented using a whole-lesion two-dimensional region of interest (ROI). Histogram-based texture analysis was performed using an in-house MATLAB-based software package (version R2021a; MathWorks, Natick, MA, USA). Extracted parameters included intensity-based metrics, dispersion measures, entropy, uniformity, and percentile values. Texture features were compared among the three groups using appropriate statistical tests. Results: Significant differences were observed among metastatic lesions according to their primary tumor origin. Significant differences were observed in the mean, median, minimum, maximum, most frequent gray-level values, root-mean-square level, root-sum-of-squares level, entropy, and all evaluated percentile parameters among groups (all p < 0.05). Pancreatic cancer metastases consistently demonstrated the highest intensity-related histogram values and percentiles, whereas breast cancer metastases exhibited the lowest values. Colorectal metastases were generally of intermediate intensity. Entropy values were significantly higher in colorectal and pancreatic metastases than in breast cancer metastases (p < 0.05), suggesting greater structural heterogeneity. No significant differences were observed for kurtosis, skewness, uniformity, or size distribution parameters (all p > 0.05). Conclusions: Ultrasound-based tissue analysis revealed distinct quantitative features among liver metastases originating from colorectal, pancreatic, and breast cancer. Density-related parameters, percentiles, and entropy show the potential to differentiate metastatic lesions based on their primary tumor origin, thus serving as a non-invasive biomarker. Full article

Background/Objectives: Pancreatic metastases are uncommon and may resemble primary pancreatic neoplasms on imaging, making tissue confirmation essential. This study aimed to characterize pancreatic metastases diagnosed by endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) and to describe tissue adequacy within the confirmed cohort and procedure-related adverse events. Methods: This retrospective, single-center study included 21 patients with histologically confirmed pancreatic metastases diagnosed by EUS-FNB between January 2021 and November 2025. Clinical data, EUS features, procedural parameters, histopathological findings, management, and outcomes were reviewed. Results: The mean age was 60.9 ± 12.9 years, and 57.1% of patients were male. Lung carcinoma was the most frequent primary tumor (33.3%), followed by renal cell carcinoma (19.0%). Most lesions were solitary (66.7%) and hypoechoic (85.7%). All 21 patients included in the final cohort had histologically adequate EUS-FNB specimens; this finding reflects the selected cohort of confirmed metastatic cases and should not be interpreted as an overall adequacy rate or measure of diagnostic performance. The mean number of needle passes was 1.14 ± 0.36. One small, asymptomatic intrapancreatic hematoma occurred and resolved conservatively. Three selected patients underwent surgical resection and were alive without evidence of disease at last follow-up; however, no inference regarding a survival benefit from surgery can be made from this small, selected subgroup. Conclusions: In this cohort of histologically confirmed pancreatic metastases, EUS-FNB provided tissue suitable for pathological characterization, with immunohistochemical analysis performed when required to determine tumor origin. The present study was not designed to estimate overall diagnostic accuracy or adequacy. Surgical resection may be considered in carefully selected patients with isolated disease, as supported by the published literature; however, the present cohort does not permit assessment of a survival benefit associated with surgery. Full article

Pancreatic ductal adenocarcinoma is one of the most aggressive tumours, with an estimated 5-year overall survival rate of 5% and median survival of 5–11 months. Approximately one third of patients die of complications due to local disease progression, especially among patients with borderline resectable or locally advanced disease; hence achieving local control is significant for improved survival outcomes. Stereotactic body radiotherapy (SBRT) allows safe and effective delivery of ablative doses of radiation and is associated with improved locoregional tumour control and progression free survival. Our article describes the rationale and the safe and effective delivery of Linac-based SBRT treatment for pancreatic cancer. Full article

Pancreato-hepatobiliary (HPB) malignancies—pancreatic ductal adenocarcinoma (PDAC), hepatocellular carcinoma (HCC), and the biliary tract cancers (BTC) comprising intrahepatic, perihilar and distal cholangiocarcinoma, gallbladder carcinoma, and ampullary adenocarcinoma—together constitute one of the heaviest and fastest-growing burdens in global oncology. Liver cancer is the third leading cause of cancer death worldwide, and pancreatic cancer, with a mortality-to-incidence ratio approaching unity, is projected to become the second leading cause of cancer death in high-income countries. This narrative review synthesises PubMed-indexed evidence across the full clinical arc of all three disease families, organised around epidemiology and risk; diagnosis, staging and biomarkers; surgical and multimodal management; and the rapidly evolving systemic therapy landscape, with survival and prognosis integrated throughout. Three cross-cutting narratives emerge. First, HPB cancers are united by late presentation, biological aggressiveness, and dependence on a background of organ dysfunction (cirrhosis in HCC, biliary obstruction in BTC and PDAC, and chronic pancreatitis as a major predisposing background in PDAC) that constrains therapy. Second, their trajectories are diverging: HCC has achieved the largest proportional survival gain of any solid tumour, driven by surveillance and immunotherapy in the subset of patients who reach specialist care; BTC has entered a nascent precision-oncology era in which FGFR2, IDH1, HER2, and BRAF alterations are druggable and immune-chemotherapy is first-line standard, although absolute survival gains remain modest and access to comprehensive molecular profiling is uneven; whereas PDAC has improved only incrementally, its immunosuppressive stroma and near-universal KRAS driver remaining formidable barriers. Third, molecular profiling, multidisciplinary care, and surgical centralisation are now non-negotiable structural determinants of outcome. We conclude that HPB oncology has entered a phase of real but unevenly distributed progress: long-term survival remains poor for most patients globally, and translating these advances into population-level gains will require earlier detection, broader access to molecular profiling and novel therapies, and biology-driven innovation. Full article

Immune checkpoint blockade has changed the management of several digestive system cancers, but its impact is highly context dependent. This review evaluates evidence for esophageal, gastric and gastroesophageal junction, colorectal, hepatocellular, biliary tract and gallbladder, and pancreatic cancers. Randomized phase III trials have established chemoimmunotherapy or dual-checkpoint strategies in advanced esophageal cancer, biomarker- and regimen-dependent first-line therapy in gastric cancer, PD-1-based therapy for MSI-H/dMMR colorectal cancer, atezolizumab–bevacizumab and STRIDE for unresectable hepatocellular carcinoma, and chemoimmunotherapy for advanced biliary tract cancer. Recent results also expand perioperative treatment: neoadjuvant checkpoint blockade produces high pathological response rates in dMMR colon cancer, adjuvant atezolizumab plus mFOLFOX6 improves disease-free survival in stage III dMMR colon cancer, and perioperative serplulimab improves event-free survival in PD-L1-positive resectable gastric cancer. These advances coexist with important negative findings. Pembrolizumab-containing therapy did not meet superiority end points in KEYNOTE-062, the initial adjuvant signal in IMbrave050 was not sustained, and unselected pancreatic ductal adenocarcinoma remains largely resistant to checkpoint blockade. Early vaccine, cellular, TIGIT, radiomics, spatial, and multi-omics studies remain hypothesis-generating and require external or randomized validation. Clinical interpretation should integrate evidence maturity, biomarker validity, immune-related toxicity, patient-reported outcomes, cost, access, and manufacturing demands rather than response rate alone. Full article

Background: Tumor hypoxia is a major determinant of radioresistance, limiting oxygen-mediated fixation of radiation-induced DNA damage and promoting metabolic adaptation, tumor aggressiveness, and treatment failure. Nitroimidazole derivatives and related hypoxia-targeting compounds have been investigated as radiosensitizers because of their oxygen-mimetic properties and selective activation under low-oxygen conditions. Methods: A structured narrative review was conducted to evaluate recent evidence on hypoxia-targeting strategies and nitroimidazole-based radiosensitizers combined with radiotherapy. PubMed and Scopus were searched in March 2026 using terms related to radiotherapy and nitroimidazoles. Studies published within the last five years were included if they investigated hypoxia-targeting compounds, radiosensitization strategies, or dose–response relationships relevant to radiotherapy. Preclinical, computational, and clinical studies were considered. Results: Sixteen studies were included, comprising preclinical, computational, and clinical investigations. Most studies were preclinical and evaluated in vitro cell lines, murine tumor models, or xenografts across multiple tumor types, including head and neck cancer, glioblastoma, breast cancer, colorectal cancer, cervical cancer, renal carcinoma, pancreatic cancer, and ovarian-related models. Nitroimidazole-based and related hypoxia-targeting strategies generally enhanced radiation response under hypoxic conditions, with sensitizer enhancement ratio values ranging from approximately 1.09 to 1.65. In vivo studies reported reductions in tumor growth or tumor volume when radiosensitizers were combined with radiotherapy. Clinical evidence, mainly in head and neck squamous cell carcinoma, showed variable effects on locoregional outcomes. Conclusions: Current evidence supports the biological relevance of hypoxia-targeting strategies for improving radiotherapy response. Nitroimidazole-based compounds show consistent radiosensitizing effects in preclinical models, but clinical translation remains heterogeneous. Future studies should integrate hypoxia imaging, standardized endpoints, advanced drug delivery systems, and clinically relevant radiotherapy models to better define their role in modern radiation oncology. Full article

Epilobium parviflorum Schreb. is a medicinal plant used traditionally against inflammatory disorders whose cytotoxic potential is still incompletely revealed. The current study investigates the phytochemical composition and in vitro cytotoxic activity of four hydroalcoholic extracts prepared from the aerial parts of E. parviflorum by using maceration and Soxhlet extraction. The extracts were characterized in terms of total phenolic, flavonoid and tannins composition and LC-MS was used to identify its individual polyphenols. Their biological effects were assessed against four cancer cell lines (A375 melanoma, HT-29 colorectal adenocarcinoma, PANC-1 pancreatic carcinoma and SK-OV-3 ovarian adenocarcinoma cells), while using HaCaT keratinocytes as healthy cells in order to assess selectivity. Cell viability, cytoskeletal and nuclear morphology, mitochondrial respiration and network pharmacology were further investigated. A complex phenolic profile was revealed, with hyperoside being identified as the main component in all extracts while the extraction parameters strongly influenced the recovery of various phenolic compounds. All extracts reduced cancer cell viability in a dose-dependent manner after 24 h exposure, with the most pronounced effects observed at 720 and 1000 μg/mL, while HaCaT cells were left relatively unaffected. The morphological assessment indicated nuclear condensation, fragmentation and cytoskeletal disruption following the application of extracts. Moreover, high-resolution respirometry showed reduced oxidative phosphorylation and electron transfer system capacity thus indicating that early mitochondrial dysfunction may contribute to the cytotoxic effects. Network pharmacology revealed that ERBB2, CTNNB1, HSP90AA1 and HDAC6 might act as molecular targets in melanoma. Thus, these findings support the hypothesis that E. parviflorum hydroalcoholic extracts, particularly the 40% ethanol Soxhlet extract, may serve as important sources of bioactive phytocompounds with antiproliferative and apoptotic properties. Full article

A standardized extract of cultured Lentinula edodes mycelia (ECLM), commercially known as AHCC^®, shows anti-inflammatory, immunomodulatory, and organ-protective properties. Experimental studies have indicated that ECLM modulates innate and adaptive immunity, including natural killer (NK) cell activity, antigen-presenting cell function, T-cell responses, and cytokine balance. These effects are particularly relevant in oncology because surgical stress and ischemia–reperfusion injury (IRI) generate a transient perioperative environment characterized by immune suppression, inflammation, and conditions favorable for metastatic progression. Recent animal studies have demonstrated the protective effects of ECLM in intestinal and hepatic IRI models, providing a potential mechanistic rationale for improving the perioperative host microenvironment. Clinical studies on hepatocellular carcinoma, pancreatic cancer, and gynecological malignancies suggest that ECLM may offer potential benefits in immune preservation, nutritional support, symptom management, and recurrence prevention, although most studies are small and hypothesis-generating. Emerging evidence from patient-derived xenograft and spontaneous carcinogenesis models further suggests that ECLM may influence tumor biology beyond host immune activation, although the underlying mechanisms require elucidation. This review summarizes the mechanistic, preclinical, translational, and clinical evidence supporting the use of ECLM as a candidate for perioperative immunonutritional strategies. We propose the hypothesis that ECLM may function as a perioperative microenvironmental stabilizer that integrates immune preservation and intestinal barrier protection. Full article

Background: Pancreatoblastoma (PB) is an exceptionally rare malignant epithelial neoplasm of the pancreas that recapitulates the developing pancreatic anlage. It is defined histologically by acinar-predominant differentiation with characteristic squamoid nests, and it may also show ductal and endocrine differentiation within the same tumor, features that distinguish it from acinar cell carcinoma and solid pseudopapillary neoplasm but that are readily overlooked. It occurs predominantly in young children, although adult-onset disease is well documented. We provide a population-based characterization of PB across the full age spectrum and benchmark it against pancreatic ductal adenocarcinoma (PDAC). Methods: Cases diagnosed between 2000 and 2021 were identified in the Surveillance, Epidemiology, and End Results (SEER) 17-registry database using site and histology codes. Cancer-specific survival (CSS) was estimated and compared, and Cox proportional hazards regression was used to explore associations with cancer-specific mortality. Results: Thirty-nine cases of PB were identified, compared with 155,924 cases of PDAC. The median age at diagnosis was 17 years (range, under 1 to 78 years); 12.8% (n = 5) were younger than 1 year. Males accounted for 69.2% (n = 27) of cases. The cohort was divided at the conventional pediatric-to-adult threshold of 18 years into a pediatric subgroup (age < 18 years; n = 20) and an adult subgroup (age ≥ 18 years; n = 19). CSS at 1 and 5 years was 95.0% and 83.5% in the pediatric subgroup, versus 67.7% and 24.6% in the adult subgroup (log-rank p < 0.001). Five-year CSS was 44.8% in males and 75.0% in females. In an exploratory multivariable model, older age was associated with higher cancer-specific mortality both as a dichotomous variable (adjusted hazard ratio [HR] for age ≥ 18 years 10.7, 95% confidence interval [CI] 2.4–48.2; p = 0.002) and, in a parallel model, as a continuous variable (adjusted HR 1.4 per 10-year increment, 95% CI 1.1–1.8; p = 0.002), indicating an age–mortality gradient. Male sex showed an association in the same direction that did not reach statistical significance (adjusted HR 3.3, 95% CI 0.96–11.6; p = 0.06). Relative to PDAC, PB was more frequently diagnosed in males and was associated with markedly superior survival (1- and 5-year CSS 81.8% and 54.9%, versus 28.8% and 4.0%). Conclusions: Pancreatoblastoma is predominantly a malignancy of young males and carries a substantially more favorable prognosis than PDAC, but outcomes differ markedly across the age spectrum, with adult-onset disease showing considerably poorer survival. Translationally, these population-level estimates support age-stratified prognostic counseling, argue for the referral of adults to centers experienced in rare pancreatic tumors, and provide a rationale for prospective molecular profiling to determine whether adult and pediatric PBs are biologically distinct and whether Wnt/beta-catenin pathway activation is therapeutically actionable. Full article

As a result of investigation of glycosidic composition of the sea cucumber Ocnus glacialis (Cucumariidae, Dendrochirotida) two new glycosides, glacialisosides A (1) and B (2), were isolated. Their structures were established by in-depth analysis of ¹H, ¹³C NMR, 1D TOCSY, and 2D NMR (¹H,¹H COSY, HMBC, HSQC, ROESY), in addition to HR-ESI mass spectra. The structures of the obtained desulfated derivatives 3, 4 were elucidated by HR-ESI-MS and ESI-MS/MS. The aglycone moieties of these glycosides are known from other glycosides of four species belonging to the order Dendrochirotida. However, despite sharing common sugar compositions and architectures, the carbohydrate chains of 1, 2 are novel due to the distinct positioning of sulfate groups. Glacialisosides A (1) and B (2) exhibit structural features shared with compounds from sea cucumbers of the orders Holothuriida, Elasipodida, and Dendrochirotida. The hemolytic and cytotoxic activities of compounds 1–4 were studied against human erythrocytes and four breast cancer cell lines (MCF-7, T-47D, MDA-MB-231, and MDA-MB-468), as well as the non-tumorigenic mammary epithelial cell line MCF-10A and the pancreatic epithelioid carcinoma cell line PANC-1. The sulfated native compounds 1 and 2 were significantly more potent than desulfated derivatives 3 and 4 across all tested cell lines, indicating a positive contribution of sulfate groups to bioactivity. Notably, the normal epithelial MCF-10A cells exhibited resistance to the membranolytic action of the glycosides, an important and favorable feature, particularly given the pronounced cytotoxicity observed against the triple-negative MDA-MB-231 cell line. Furthermore, glacialisoside A (1) demonstrated potent inhibitory activity against the formation and growth of MDA-MB-468 cell colonies, effectively blocking cell division even at concentrations below 0.2 μM and completely halting it at a dosage of 1 μM. Thus, the colony formation assay reveals a latent sensitivity of cancer cells—not only to the membranolytic action of triterpene glycosides, but also to the effects of these compounds relevant to other aspects of cell survival, division, and spread. Full article

The underexplored Passerini–Smiles reaction (PSR), a variant of the 3-component Passerini reaction (3CPR), was successfully employed to create a tailored library of phenoxy-indoline carboxamide derivatives based on a fragment-based hybrid drug design strategy. Under mild conditions, inexpensive and commercially available isatin was utilized as a privileged carbonyl core, combined with electron-deficient phenols to establish a highly functionalized framework. Post-Passerini–Smiles transformations leveraged this strategic layout to provide a step-economical route to a complementary library of three-dimensional spirooxindole hybrids derived from the PS adducts. This study reinforces the relevance of combining structural hybridization with multicomponent reaction strategies in the discovery of potential anticancer active pharmaceutical ingredients (APIs). Both libraries were evaluated against six human solid-tumor cell lines, including non-small cell lung carcinoma, cervical and colon adenocarcinoma, and breast and pancreatic cancers. The most active compound 4gaa exhibited GI₅₀ values below 10 μM for most of the tested cancer cell lines. Full article

Clear cell renal cell carcinoma (ccRCC), hepatocellular carcinoma (HCC), lung adenocarcinoma (LUAD), and pancreatic ductal adenocarcinoma (PDAC) are highly lethal cancers that share molecular mechanisms underlying tumor progression, yet common biomarkers across these cancers remain largely unexplored. Microarray datasets for the four cancers were analyzed to identify differentially expressed genes (DEGs) using adjusted $p<0.05$ and $\left|{\log }_2\mathrm{FC}\right|>1$ as significance thresholds. Disease-associated gene targets were collected from CTD, DISEASES, and GeneCards databases. Shared genes were identified across cancers, and functional enrichment analysis revealed their involvement in key cancer-related pathways, particularly the cell cycle. Protein–protein interaction networks identified ten candidate hub biomarkers (HGF, CDK1, CCNB1, RRM2, KIF14, DCN, SERPINE1, CCNA2, DLGAP5, and MAD2L1) consistently dysregulated across all four cancers. Survival analysis supported their potential as therapeutic targets, correlating with poor prognosis. These findings highlight candidate pan-cancer biomarkers for improved diagnosis and therapy. Full article

Background: Liver cancers are a major cause of morbidity and mortality in patients where effective, non-invasive treatment options remain limited. Objective: Histotripsy is a non-invasive, non-thermal, image-guided focused ultrasound method of ablation that mechanically disrupts cells and offers a range of potential advantages over other ablation modalities. The lack of physiologically and anatomically relevant animal models of human liver cancer has significantly hindered biomedical device development, including histotripsy. Methods: To address these limitations, we developed a clinically relevant large animal orthotopic, dual-tumor model of human liver cancer and utilized these unique animals to evaluate the safety and efficacy of histotripsy. Here, we utilized immunocompromised pigs with genetic modifications in their IL-2RG and RAG2 genes and orthotopically engrafted human hepatocellular carcinoma (HepG2/C3A) and pancreatic adenocarcinoma (Panc-1) cells within the liver. The models were designed to recapitulate primary and metastatic liver tumor phenotypes. Results: Histotripsy enabled real-time visualization of the treatment by the formation of bubble clouds and accurate targeting of the lesions. Histological analysis confirmed the engraftment of tumor cells and the ablation of targeted tissue. Serum biomarkers demonstrated no significant differences in bilirubin, ALT, ALKP, or CK post-treatment, suggesting that histotripsy treatment was well tolerated with minimal hepatic dysfunction or hepatocellular injury. Conclusions: These findings establish a novel, clinically relevant porcine model of primary and metastatic liver tumors and demonstrate the safety and feasibility of using this model for evaluating histotripsy as a noninvasive modality for precise tumor ablation. Full article

Background/Objectives: To date there is a lack of an integrative review literature on redox homeostasis, oxidative stress and the influence on metabolic pathways and plasticity in uveal melanoma (UM), since most literature findings are from cutaneous melanoma (CM), a genetically and behaviorally distinct cancer. Furthermore, UM metabolic pathway comparison to other cancers could provide more insight into metastatic UM, a difficult-to-treat malignancy. Methods: A wide-ranging multi-step literature search of PubMed and Web of Science for redox balance, oxidative stress, antioxidants and metabolic plasticity in UM, with expanded search terms for connections with other cancers. Results: UM cells maintain redox homeostasis via several redox loops: glutathione, thioredoxin, peroxiredoxins, peroxisomal catalase and the mitochondrial antioxidative network. NADPH plays a key role in regenerating UM antioxidative capabilities. Key redox signaling pathways are the subject of ongoing research in UM: NRF2 signaling, AMPK, mTOR, MAPK, FoxO. These pathways are less studied versus CM and present behavior differences in UM. PON2, studied in CM, represents a literature gap in UM. Inside the tumoral microenvironment, UM presents high metabolic plasticity and easy switching from glycolysis to oxidative phosphorylation (OXPHOS). Thus, UM eschews the classic Warburg effect loop and instead presents high oxidative phosphorylation (OXPHOS) gene expression, which generates additional lactate, which in turn produces cascade reprogramming in the metabolic pathways and lactate metabolism particularities associated in experimental studies with immune-escape phenomena. Uveal melanoma’s OXPHOS capabilities confer survival advantages and subdivide tumoral populations into OXPHOS-high and OXPHOS-low variants. Glycolysis/OXPHOS metabolic plasticity is an ongoing research field in other cancers with common and different elements vs. UM: cutaneous melanoma, small cell lung carcinoma, pancreatic cancer, breast cancer, acute myeloid leukemia, prostate cancer, renal cell carcinoma and glioblastoma. Uveal melanoma cells are susceptible to deleterious effects of prooxidants, a metabolic vulnerability which helps to create genetic pleomorphism, selecting higher proliferation and dissemination variants. Conclusions: Uveal melanoma is an oncogenic mutation and mitochondrial metabolism-driven malignancy, with metabolic connections to other malignancies. Emerging understanding of redox homeostasis, redox pathway signaling, mitochondrial oxidative and oncogenic metabolism could lead to better understanding of therapeutic response and new therapeutic targets. This review novelly integrates the general and CM redox literature with the UM literature, painting a complex redox signaling and metabolic plasticity picture of UM. Full article

Background: The molecular changes associated with the progression of intraductal papillary mucinous neoplasm (IPMN) to pancreatic ductal adenocarcinoma (PDAC) and distant metastasis remain incompletely understood. Case Presentation: A man in his late 70s underwent pancreaticoduodenectomy and partial hepatectomy for a pancreatic head tumor with synchronous liver metastasis. Histology showed a 4.5 cm moderately differentiated PDAC arising in an IPMN with high-grade dysplasia (pT3N1M1). Genomic analysis of the IPMN, PDAC, and liver metastasis identified KRAS p.G12D, CDKN2A deletion, and GNAS p.R201H in the IPMN; additional SMAD4 p.R361C in the PDAC; and KRAS p.G12D, CDKN2A deletion, SMAD4 p.R361C, and APC p.R1450Ter in the liver metastasis. The APC alteration was confirmed by targeted sequencing and was accompanied by loss of heterozygosity at the APC locus. β-Catenin showed membranous expression in the IPMN and PDAC, but nuclear accumulation in the liver metastasis. Discussion: The shared KRAS, CDKN2A, and SMAD4 alterations support a common clonal origin of the PDAC and metastatic tumors. The absence of a detectable GNAS alteration in the liver metastasis and the presence of a metastasis-specific APC alteration are compatible with, but do not prove, branching evolution and selection of a metastatic subclone. Conclusions: This case shows a metastasis-specific heterozygous APC truncating alteration with loss of heterozygosity, accompanied by nuclear β-catenin accumulation, in an IPMN-associated PDAC. Full article