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Background. Contributions of tumor-derived extracellular vesicles, TEX, to tumor progression and metastasis involve their crosstalk with immune cells in the tumor microenvironment. This crosstalk results in metabolic reprogramming of immune cells from anti-tumor to pro-tumor activity. Mechanistic underpinnings of the TEX entry and delivery of molecular signals responsible for metabolic reprogramming may be unique for different types of immune cells. Methods. An in vitro model of THP-1 myeloid cells co-incubated with TEX illustrates the role TEX play in polarization of macrophages to TAMs. Results. In THP-1 cells, the dominant signaling pathway of melanoma cell-derived TEX involves HSP-90/TLR2. This leads to activation of the NF-κB and MAP kinase pathways and initiates THP-1 cell polarization from M0 to M2 with strong expression of immunosuppressive PD-L1. TEX may be seen as “danger” by the myeloid cells, which utilize the pattern recognition receptors (PRR), such as PAMPs or DAMPs, for engaging the complementary ligands carried by TEX. The same melanoma TEX signaling to T cells via DAMPs induced mitochondrial stress, resulting in T-cell apoptosis. Conclusions. As the signaling receptors/ligands in TEX are determined by the tumor, it appears that the tumor equips TEX with an address recognizing specific PRRs expressed on different recipient immune cells. Thus, TEX, acting like pathogens, are equipped by the tumor to alter the context of intercellular crosstalk and impose a distinct autophagy-not-apoptosis signature in recipient THP-1 cells. The tumor might endorse TEX to promote tumor progression and metastasis by enabling them to engage the signaling system normally used by immune cells for defense against pathogens.

7 January 2026

Uptake of MTEX labeled with the MemGlowTM 590 dye by THP-1 cells. Flow cytometry (left panel) and confocal microscopy (right panel) show a rapid entry of MTEX into the cytosol of THP-1 cells.

Background: Minimally invasive pancreatoduodenectomy (MIPD) has evolved from an experimental technique to a feasible surgical option for pancreatic cancer in selected settings. However, its oncologic adequacy, safety, and generalizability remain debated, particularly given the biological aggressiveness of pancreatic ductal adenocarcinoma (PDAC) and the technical complexity of the procedure. Methods: This narrative review critically summarizes contemporary evidence regarding MIPD for pancreatic cancer, with particular attention to randomized controlled trials (RCTs), meta-analyses, and large observational studies. We distinguish findings derived from mixed periampullary tumor cohorts from those specific to PDAC and evaluate methodological limitations, learning-curve effects, and sources of heterogeneity across studies. Results: Recent RCTs and meta-analyses demonstrate that, when performed by experienced surgeons in high-volume centers, MIPD achieves perioperative outcomes comparable to open pancreatoduodenectomy, with advantages including reduced blood loss, shorter hospital stay, and faster functional recovery. Importantly, oncologic parameters such as R0 resection rates and lymph node yield appear equivalent between approaches, although robust long-term survival data from PDAC-specific RCTs remain lacking. Emerging evidence supports the feasibility of MIPD in complex clinical scenarios, including after neoadjuvant therapy, in frail or elderly patients, and in selected cases requiring vascular resection. Nonetheless, outcomes are strongly influenced by surgeon experience, institutional volume, and patient selection. Cost-effectiveness analyses and data from lower-volume centers remain limited. Conclusions: Current evidence supports MIPD as a viable alternative to open surgery for pancreatic cancer in carefully selected patients treated at specialized centers. However, claims of oncologic superiority are premature. Future research should focus on PDAC-specific randomized trials, standardized quality metrics, and strategies to mitigate learning-curve and resource-related barriers to broader implementation.

7 January 2026

Background: Pancreatic cancer (PC) is a refractory malignancy with a dismal prognosis. For unresectable PC, gemcitabine plus nab-paclitaxel (GnP) is widely used as first-line chemotherapy. During treatment, patients may require unplanned hospitalization (UPH) due to tumor progression, biliary obstruction, or chemotherapy-related adverse events. Although UPH during chemotherapy may be linked to poorer survival, its prognostic impact as a time-dependent clinical event during active treatment has not been empirically evaluated in unresectable PC. We investigated the prognostic impact of UPH occurring during first-line GnP therapy. Objective: To clarify the association between UPH during first-line GnP and overall survival (OS). Methods: We retrospectively analyzed 189 patients with histologically confirmed unresectable PC who received first-line GnP at our institution between February 2016 and February 2023. The occurrence of UPH during GnP and the reason for the first UPH were categorized. Associations with OS were assessed using the Kaplan–Meier method and Cox proportional hazards models, including a time-varying covariate (TVC) analysis. Risk factors for UPH were examined with logistic regression. Results: UPH occurred in 76 patients (40.2%) during GnP. Pancreatic head tumors and pre-treatment biliary drainage were significantly more frequent in the UPH group. Median OS was 10.88 months in the UPH group versus 19.23 months in the non-UPH group; UPH was a significant adverse prognostic factor (hazard ratio [HR] 1.97, p < 0.01). In multivariable analysis incorporating a TVC, UPH remained an independent predictor of worse prognosis (HR 3.02, p < 0.01). Reasons for first UPH were progression (n = 28), recurrent biliary obstruction (RBO; n = 26), GnP-related adverse event (AE; n = 16), and other (n = 6). Hospitalization due to progression or RBO was associated with poorer survival. Pancreatic head location was identified as a risk factor for UPH. Conclusions: UPH during first-line GnP is an independent adverse prognostic factor in patients with unresectable PC, even after accounting for TVC. In pancreatic head cancer, closer monitoring for biliary and obstructive complications may be particularly important during treatment.

7 January 2026

Nuclear Imaging in Renal Cell Carcinoma: Current Evidence and Clinical Applications

  • Abdullah Al-Khanaty,
  • Shane Qin and
  • Carlos Delgado
  • + 12 authors

Introduction: Radiotracer-based nuclear imaging, including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), can complement conventional cross-sectional imaging in renal cell carcinoma (RCC) by providing biological characterisation of tumour metabolism, angiogenesis, hypoxia, and the tumour microenvironment. While computed tomography (CT) and magnetic resonance imaging (MRI) remain the diagnostic standard, accumulating evidence suggests that selected nuclear imaging techniques may offer incremental value in specific clinical scenarios. Methods: A narrative literature review was performed using PubMed, Embase, and Web of Science to identify preclinical, retrospective, and prospective studies evaluating PET and SPECT radiotracers in localised and metastatic RCC. Priority was given to meta-analyses, multicentre prospective trials, and studies with histopathological correlation. Results: [18F]fluorodeoxyglucose (FDG) PET/CT demonstrates limited sensitivity for primary renal tumours (pooled sensitivity of approximately 60%) but performs substantially better in metastatic and recurrent disease (pooled sensitivity and specificity of approximately 85–90%), where uptake correlates with tumour grade, progression-free survival, and overall survival. [99mTc]sestamibi SPECT/CT differentiates oncocytoma and hybrid oncocytic/chromophobe tumours from malignant RCC with pooled sensitivity and specificity of around 85–90%, supporting its role in evaluating indeterminate renal masses rather than staging. Prostate-specific membrane antigen (PSMA) PET/CT shows high detection rates in clear-cell RCC, particularly in metastatic disease, with reported sensitivities of approximately 85–90% and management changes in up to 40–50% of selected cohorts. Carbonic anhydrase IX (CAIX)-targeted PET/CT enables the biologically specific visualisation of clear-cell RCC, achieving sensitivities and specificities in the range of 85–90% in prospective phase II and III trials for primary tumour characterisation. Fibroblast activation protein inhibitor (FAPI) PET/CT demonstrates high tumour-to-background uptake in early RCC studies, but evidence remains preliminary, with small cohorts and recognised non-specific uptake in benign inflammatory and fibrotic conditions. Conclusions: Radiotracer-based nuclear imaging provides complementary, biology-driven insights in RCC that extend beyond anatomical assessment. While most modalities remain adjunctive or investigational and are not recommended for routine use, selective application in carefully chosen clinical scenarios may enhance tumour characterisation, prognostication, and personalised treatment planning.

7 January 2026

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Cancers - ISSN 2072-6694