Search Results (7,821)

Background/Objective: Crohn’s disease exclusion diet (CDED) is used to induce remission and maintenance treatment of Crohn’s disease (CD), but its efficacy as adjuvant treatment of biological agents is not clear, especially for children with CD in China. The aim is to compare the synergistic induction of remission, as well as the effects on physical growth and nutritional indicators, of the CDED and Exclusive Enteral Nutrition (EEN), when used alongside infliximab as adjunctive therapies for children with CD. Methods: A retrospective analysis was conducted on newly diagnosed children with CD who were receiving infliximab treatment in combination with either CDED or EEN at the Department of Gastroenterology at Beijing Children’s Hospital between April 2022 and June 2025. The patients were divided into two groups: CDED and EEN. Changes in disease activity, physical growth indicators, nutritional status, and inflammatory markers were then compared between the two groups at six and twelve weeks post-treatment. Results: A total of 45 children with CD who met the inclusion and exclusion criteria were included in the study. Of these, 27 were boys (60%) and 18 were girls (40%), with an average age of (11.6 ± 2.9) years. Based on nutritional intervention, 19 patients were assigned to the CDED group and 26 to the EEN group. The clinical remission rates were 89.5% and 94.7% at 6 and 12 weeks post-treatment, respectively, in the CDED group and 88.5% and 84.6%, respectively, in the EEN group. At 12 weeks, the endoscopic remission rates were 47.1% (8/17) and 24.0% (5/26), respectively, in the CDED and EEN groups. There were no statistically significant differences between the two groups in terms of clinical remission or endoscopic remission (p > 0.05). Comparisons of physical growth indicators showed that, after 6 and 12 weeks of treatment, children in the CDED group had a significantly higher body mass index (BMI) for age Z-score than those in the EEN group (p < 0.05). Comparisons of serum nutritional and inflammatory markers revealed that, after 12 weeks of treatment, fecal calprotectin levels were significantly lower in the CDED group than in the EEN group (p < 0.05), with no significant differences observed in other markers. Conclusions: For children with moderate-to-severe or high-risk factors, CDED and EEN therapy as adjunctive treatment to infliximab demonstrate comparable efficacy in inducing disease remission. However, CDED was more effective than EEN at improving physical growth and reducing intestinal inflammation. Full article

Background/Objectives: Juzentaihoto (JTT), a traditional Kampo formula composed of ten medicinal herbs, is widely prescribed in Japan for immune enhancement and general health maintenance. This exploratory, open-label pilot study aimed to evaluate the feasibility and immunomodulatory effects of JTT in cancer patients and to explore its potential mechanisms of action. Methods: Ten cancer patients received oral JTT (7.5 g/day) for 14 days, while healthy volunteers served as a reference group. Peripheral natural killer (NK) cell phenotypes and CD95 expression were analyzed by flow cytometry, and serum Fas ligand (FasL) concentrations were measured by ELISA. Complementary in vitro assays using PBS-extracted, autoclaved JTT were conducted to assess Fas/FasL-mediated apoptosis in Jurkat and primary T cells by flow cytometry and Western blotting for cleaved caspase-8 and -3. Additional experiments with staurosporine (intrinsic apoptosis) and TRAIL in OSC-19 carcinoma cells were performed to determine pathway specificity. Results: In patients, most NK-cell markers showed no statistically significant within-subject changes, although a trend-level increase in NKp46 and a significant reduction in NK-cell CD95 expression (paired p = 0.014) were observed. Between-group differences primarily reflected baseline disparities between cancer patients and healthy controls. In vitro, JTT (50–100 µg/mL) partially attenuated FasL-induced apoptosis and reduced cleaved caspase-3 without affecting cleaved caspase-8, suggesting selective downstream modulation of the extrinsic pathway. Conclusions: Within the limitations of a small, non-randomized cohort without placebo, these findings are hypothesis-generating and indicate that JTT selectively modulates Fas-mediated lymphocyte apoptosis without promoting tumor immune evasion. Further randomized trials and mechanistic studies incorporating co-culture or 3D tumor–immune models are warranted to confirm these observations and identify active constituents. Full article

Cancer development in BRCA1 carriers is a multi-step process, which is triggered by several factors and mechanisms that are not clearly understood. Most BRCA1 carriers develop triple-negative breast cancer (TNBC)—estrogen receptor (ER)-, progesterone receptor (PR)-, and HER2 -negative cancers—which originates from ER/PR/HER2-negative breast progenitor cells. Due to a lack of ER/PR/HER2-negative cell models with BRCA mutations, the processes inducing cancer development in BRCA carriers have not been comprehensively studied. Thus, studies characterizing ER/PR/HER2-negative cells carrying a BRCA1 germline mutation are needed to gain more in-depth knowledge about the steps leading to cancer initiation in BRCA1 carriers. To study the cancer development in these patients, we established a protocol for the generation of human ER/PR/HER2-negative breast organoids carrying a BRCA1 germline mutation. We confirmed that these organoids are unresponsive to estrogen, can self-renew, and express the stem/progenitor marker CD44. In addition, we observed that these organoids contain outgrowths that resemble the mature ductal and lobular units of the mammary gland, thus making it a suitable model system to study how cancer develops in ER/PR/HER2-negative mammary cells that carry a BRCA1 germline mutation. Full article

Background and Aim: People with HIV (PWH) have historically been excluded from cancer immunotherapy trials due to concerns over immune dysregulation and safety. This systematic review evaluates the safety, efficacy, and immunologic outcomes of Programmed death-1 (PD-1) inhibitors in PWH diagnosed with non-small-cell lung cancer (NSCLC). Methods: Following PRISMA guidelines, a systematic search was conducted across PubMed, Scopus, Web of Science, and Medline through January 2025. Studies were included if they reported outcomes of ICIs in PWH with NSCLC. Data extraction included progression-free survival (PFS), overall survival (OS), immune-related adverse events (irAEs), antitumor response, HIV viral control, and immunologic parameters. Study quality was assessed using the Joanna Briggs Institute (JBI) checklist. Results: Six cohort studies (n = 762 patients) met inclusion criteria. ICIs used included nivolumab, pembrolizumab, atezolizumab, and durvalumab, with treatment durations ranging from 3.1 to 5.4 months. Median PFS ranged from 3.0 to 6.3 months, and OS ranged from 10.0 to 66.0 months. Overall response rates (ORRs) varied from 13% to 75%, and disease control rates (DCRs) ranged from 47% to 62.5%. irAEs occurred in 25% to 75% of patients, with 6–20% experiencing grade 3–4 events. Corticosteroids were required in 13–29% of patients, and treatment discontinuation due to toxicity occurred in up to 30%. Most patients had controlled HIV, with CD4 counts typically above 300 cells/μL and undetectable viral loads. Conclusions: ICIs appear safe and effective in PWH with NSCLC, with toxicity and efficacy outcomes comparable to the general population. While immunotherapy should not be withheld based solely on HIV status, better standardization in reporting HIV-related variables is needed to optimize patient selection and management. Full article

Background: Chimeric Antigen Receptor T-cell (CAR-T) cell therapy has revolutionized cancer treatment and is now being explored as a novel approach to treat refractory autoimmune diseases by targeting autoreactive immune components, especially B cells. Objective: Our aim was to provide a narrative review of the current evidence, mechanisms, efficacy, safety, and future directions of CAR-T cell therapy in autoimmune diseases. Methods: A structured literature search was conducted in MEDLINE via PubMed using keywords such as “CAR-T”, “chimeric antigen receptor T-cell”, “autoimmune diseases”, “lupus”, “rheumatoid arthritis”, “multiple sclerosis”, and “vasculitis”. Studies on CAR-T mechanisms, efficacy, safety, and clinical outcomes were included. Results: CAR-T cell therapies, especially CD19-directed constructs, demonstrated sustained drug-free remission in all patients across early SLE case series (n = 5–7), with normalization of serological markers and improved renal outcomes. Emerging preclinical and early clinical data in rheumatoid arthritis, multiple sclerosis, ANCA-associated vasculitis, juvenile autoimmune diseases, and idiopathic inflammatory myopathies also report clinical improvement and biomarker normalization. Reported adverse events in autoimmune cohorts were limited to mild cytokine release syndrome in a minority of cases, with no severe neurotoxicity or life-threatening infections, suggesting a more favorable safety profile compared to oncology settings. In parallel, next-generation innovations—including dual-target CARs, CAR-Tregs, and molecular safety switches—are advancing toward clinical translation. Conclusions: CAR-T cell therapy is emerging as a transformative strategy for autoimmune disease management, especially in refractory cases. Although initial outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key challenges. Future research should focus on optimizing cell targets, minimizing off-target effects, and improving affordability. Full article

Background: Neuromyelitis optica spectrum disorder (NMOSD) causes severe optic nerve (ON) inflammation and vision loss. Current treatments remain limited, prompting exploration of new therapeutic strategies. This study evaluated the efficacy of ITRI-E-(S)4046 (ITRI-ES), a dual ROCK1/2 and MYLK4 kinase inhibitor, in a rat model of NMOSD optic neuritis. Methods: NMOSD-like optic neuritis was induced in rats by applying NMOSD patient serum-soaked sponges around the ON. Rats received intravitreal injections of either 0.2% ITRI-ES, phosphate-buffered saline (PBS), or intraperitoneal methylprednisolone (MP). Visual function was assessed using flash visual-evoked potentials (fVEP). Retinal ganglion cell (RGC) survival and apoptosis were quantified using FluoroGold retrograde labeling and TUNEL assay. ON inflammation and demyelination were evaluated via immunohistochemistry and Western blot analysis of aquaporin-4 (AQP4), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and inflammatory markers. Results: ITRI-ES significantly preserved visual function, restoring fVEP amplitudes (~36 μV vs. ~21 μV in PBS-treated, p < 0.05) and RGC density (~85% of normal vs. ~37% PBS). RGC apoptosis was reduced (~2.3-fold lower vs. PBS, p < 0.05). PBS-treated rats showed decreased AQP4 and MBP (2.5–2.8-fold vs. sham) and increased GFAP (2.8-fold). ITRI-ES maintained higher AQP4 (~3.5-fold) and MBP (~1.5-fold) levels, suppressed GFAP (~5.5-fold vs. PBS), reduced NF-κB, IL-1β, TNF-α, microglia activation, and macrophage infiltration, and increased anti-inflammatory Arg1 and CD206 markers (~3-fold vs. PBS). Conclusions: ITRI-ES alleviates optic nerve inflammation, preserves retinal integrity, and maintains visual function in NMOSD-associated optic neuritis, underscoring kinase inhibition as a promising therapeutic strategy. Full article

Chronic hemophilic synovitis (CHS), driven by hemosiderin-laden macrophages from recurrent hemarthrosis, is a major cause of joint damage in hemophilia. Platelet-rich plasma (PRP) is a promising regenerative therapy for joint diseases. This study investigated PRP’s ability to modulate macrophage polarization from a pro-inflammatory (M1) to a pro-resolving, tissue-repairing (M2) phenotype in CHS. We analyzed synovial fluid (SF) from CHS patients (N = 22), both pre- and post-PRP treatment. Ex vivo analysis revealed a predominant M1 profile with an increased proportion of CD11⁺CD14⁺CD64^hi compared with CD206⁺ or CD163⁺ M2 macrophages in CHS SF. In vitro experiments showed that CHS SF skewed monocyte-derived macrophages toward an M1 inflammatory program, evaluated by flow cytometry, qPCR, and ELISA. However, adding PRP significantly modulated the pro-inflammatory macrophage program, promoting an M2 tissue repair profile. Furthermore, a random forest machine learning algorithm, applied to public scRNAseq data, confirmed PRP’s macrophage reprogramming effect. Functional assays also showed increased TGF-β secretion and macrophage fusion when challenged with neutrophil extracellular traps (NETs). A small patient follow-up cohort treated with intra-articular PRP showed similar results, including normalization of cellular content and reduced CD64/CD206 expression. These findings indicate that PRP treatment effectively shifts SF-associated M1 macrophages to an M2-like phenotype, highlighting its potential as a therapeutic strategy for CHS. Full article

Background: Myelosuppression is one of the most common chemotherapy side effects, seriously threatening the quality of life of cancer patients. Studies have shown that velvet antler polypeptides (VAPs) could enhance immunity and anti-aging and also have a hematopoietic-promoting effect. However, there are relatively few studies on the treatment of myelosuppression with VAPs, and the therapeutic mechanism remains unclear. Methods: This study employed both in vitro and in vivo models to explore the mechanism of VAPs against myelosuppression. In this study, the cyclophosphamide (CTX)-induced bone marrow mesenchymal stem cell (BMSC) injury model was used to evaluate the effects of VAPs on cell viability, apoptosis, reactive oxygen species activity, and protein expression. Furthermore, a CTX-induced myelosuppression mouse model was employed to evaluate peripheral blood counts, organ indices, femoral tissue histopathology, immunohistochemical expression of CD34, VEGF, and Notch1, and key proteins in the Notch1/PI3K/AKT pathway in vivo. Results: Our results showed that VAPs protected BMSCs from CTX-induced apoptosis, inhibited ROS production, and promoted the secretion of VEGF, TPO, and VCAM-1, thereby improving the bone marrow microenvironment. Furthermore, the results showed that VAPs improved the peripheral blood counts and bone marrow nucleated cell (BMNC) count in CTX-induced myelosuppression mice and ameliorated pathological injury of the spleen, thymus, and liver. VAPs inhibited the apoptosis of bone marrow cells, manifested by regulating the expression levels of proteins like PI3K/p-PI3K, AKT/p-AKT, Bcl-2, Bax, and Caspase-3. Simultaneously, it upregulated the expression of Notch1 and Hes1 proteins. The application of the PI3K inhibitor LY294002 and the Notch1 inhibitor DAPT demonstrated that the ameliorative effect of VAPs on myelosuppression was dependent on the activation of both the Notch1 and PI3K/AKT pathways. Conclusions: Our study indicates that VAPs may achieve treatment of myelosuppression by improving the hematopoietic microenvironment, inhibiting apoptosis of mouse bone marrow cells, and regulating the Notch1 and PI3K/AKT signaling pathways. Full article

Background: The aging of people living with HIV (PLWH) necessitates antiretroviral regimens (ART) with high efficacy, a favorable safety profile, and minimal drug–drug interactions. We evaluated the real-world performance of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in PLWH aged ≥ 50 years, stratified by prior treatment experience. Methods: This retrospective cohort study included ART-naïve and virologically suppressed treatment-experienced PLWH aged ≥ 50 years who started B/F/TAF. Primary endpoints were virological suppression (HIV-1 RNA < 50 copies/mL) at 12 months ± 1 month and 24 months ± 1 month, and safety. Changes in immunological (CD4+ count, CD4+/CD8+ ratio), metabolic, and hepatic parameters were assessed. Results: Among 214 patients (37 naïve, 177 experienced; mean age 60.6 years), high virological suppression rates were observed in both naïve (85.7%) and experienced (93.9%) cohorts at 24 months. Immunologically, naïve patients experienced a robust increase in CD4+ counts (from 176 to 450 cells/μL, p < 0.001). A key finding was a significant increase in the CD4+/CD8+ ratio in the experienced cohort, which normalized from 0.95 at baseline to 1.12 at 24 months (p < 0.001). The regimen demonstrated a favorable safety profile: metabolic parameters remained stable, and hepatic enzymes significantly improved in naïve patients. Transient elastography confirmed no worsening of liver fibrosis or steatosis in experienced patients. The overall discontinuation rate was 19.2%, driven by different reasons between cohorts (e.g., comorbidities in naïve, strategic simplification in experienced). Conclusions: This real-world study confirms that B/F/TAF is a versatile cornerstone for the management of older PLWH. It demonstrates high efficacy in initiating treatment and is a safe, effective, and durable platform for treatment simplification. Its favorable metabolic and hepatic profile makes it particularly suitable for an aging population with a high burden of comorbidities, ensuring long-term treatment success. Full article

Radionuclide molecular imaging of epidermal growth factor receptor (EGFR) expression might permit the selection of patients for EGFR-targeting therapies. Designed ankyrin repeat protein (DARPin) E01 with a high affinity to the ectodomain III of the EGFR is a possible EGFR imaging probe. The goal of this study was to evaluate the potential of radiolabeled DARPin E01 for in vivo imaging of EGFR. DARPin E01 containing the (HE)₃-tag was site-specifically labeled with a residualizing ^99mTc (using ^99mTc]Tc(CO)₃). Two methods providing non-residualizing ¹²³I labels, direct electrophilic radioiodination and indirect radioiodination using [¹²³I]I-para-iodobenzoate (PIB), were tested. [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB preserved specific binding to EGFR-expressing cells and affinity in the single-digit nanomolar range. Direct labeling with ¹²³I resulted in a substantial loss of binding. In vitro cellular processing studies showed that both [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB had rapid binding and relatively slow internalization. Evaluation of [^99mTc]Tc-(HE)₃-E01 biodistribution in normal CD1 mice showed that its hepatic uptake was non-saturable, suggesting that this tracer does not bind to murine EGFR. A side-by-side comparison of biodistribution and tumor targeting of [^99mTc]Tc-(HE)₃-E01 and [¹²³I]I-(HE)₃-E01-PIB was performed in Nu/j mice bearing EGFR-positive A-431 and EGFR-negative Ramos human cancer xenografts. Both radiolabeled DARPins demonstrated EGFR-specific tumor uptake. However, [¹²³I]I-(HE)₃-E01-PIB had appreciably lower uptake in normal organs compared to [^99mTc]Tc-(HE)₃-E01, which provided significantly (p < 0.05) higher tumor-to-organ ratios. Gamma-camera imaging confirmed that [¹²³I]I-(HE)₃-E01-PIB demonstrated a higher imaging contrast in preclinical models than [^99mTc]Tc-(HE)₃-E01. In conclusion, DARPin (HE)₃-E01 labeled using a non-residualizing [¹²³I]I-para-iodobenzoate (PIB) label is the preferred radiotracer for in vivo imaging of EGFR expression in cancer. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) are frontline treatment for advanced Merkel Cell Carcinoma (MCC), regardless of viral status. Frontline ICIs provide durable benefit to only half of patients, highlighting a need for alternative therapies. In this study, the objective is to leverage whole exome sequencing (WES) and transcriptome sequencing (WTS) to distinguish genomic alterations associated with ICI response. Investigate differential genomic alterations between virus-positive (VP) and virus-negative (VN)-MCC to identify novel therapeutic targets. Methods: A total of 95 MCC cases underwent WES and WTS. Utilizing computational pipelines applied to WES, we identified viral status and tumor mutational burden (TMB). RNA-seq data was used to characterize the immune microenvironment. Results: Of 95 MCC cases, 57 (60%) were VP-MCC and 38 (40%) were VN-MCC. Median TMB was higher in VN-MCC (27.5 vs. 1 Muts/Mb). Mutations in TP53, RB1, NOTCH1, KMTD2, KMT2C, and PIK3CA were primarily found in VN-MCC. MAPK Pathway Activity Score, NK cell infiltration, and the immune checkpoint gene CD276 in VN-MCC tumors were upregulated. No overall survival (OS) difference was identified between VP and VN-MCC, even after ICIs. Conclusions: MCC oncogenesis and treatment response transcend viral status. While mutational analysis confirms previous findings, assessment of the transcriptome and tumor microenvironment suggests alternate therapeutic targets. Full article

Cell transplantation is often performed with ultrasonographic guidance for accurate delivery through injection. In such procedures, using ultrasonographic contrast greatly improves target delivery. However, accumulating evidence suggests that exposure to such contrast agents may have negative effects on transplanted cells. No study so far has researched this issue. Stabilized sulfur hexafluoride (SF6) microbubbles are a widely used sonographic contrast agent. Skin hCD55 porcine transgenic fibroblasts and mesenchymal stem cells from human bone marrow (hMSCs) were exposed in vitro to SF6 in concentrations ranging from 1.54 µM to 308 µM. The effects on viability and cell growth were registered using an impedance-based label-free Real-Time Cell Analyzer (RTCA). Data was recorded every 15 min for 50 h of total study time. Both cell lines behave distinctly when exposed to SF6. Porcine fibroblast growth showed relevant alterations only when exposed to higher concentrations. In contrast, hMSCs showed progressive growth decrease in relation to SF6 concentration. Taken together, while SF6-based contrast agents pose no threat to patient safety, our results indicate that exposure of suspended stem cells to the contrast agent could affect the effective dose administered in cell therapy procedures. This prompts specific cell lineage testing, adjusting methods and properly compensating for cell loss, with a potential impact on procedural cost and success rates. Full article

Thrombosis is a common complication in multiple myeloma (MM) patients treated with immunomodulatory drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide. When combined with anti-CD38 monoclonal antibodies, these agents are highly effective but may increase thrombotic events (TE), potentially delaying therapy. This exploratory, hypothesis-generating analysis, conducted within the MMVision mono-institutional prospective study, included 53 MM patients who initiated IMiD plus anti-CD38 therapy between May 2021 and December 2022 (median follow-up: 18 months). Treatment regimens comprised lenalidomide (n = 36) or thalidomide (n = 15) with daratumumab, and pomalidomide (n = 2) with isatuximab. Most patients (n = 38) received frontline therapy, and all were given thromboprophylaxis according to guidelines, mainly aspirin (73%). Five patients (9.4%) developed VTE after a median of 48 days, managed with short-term low-molecular-weight heparin (LMWH). Exploratory analysis of 27 clinical/laboratory parameters suggested possible associations between VTE and low levels of beta-2 microglobulin, ferritin, intact/free lambda light chains, and monocyte-to-lymphocyte ratio. Notably, four of the five VTEs occurred in patients without lytic bone disease, typically associated with bone-driven inflammation in MM. Although all patients received aspirin prophylaxis from treatment initiation, it remains unclear whether thrombosis would also have occurred among those with higher inflammatory burden. These preliminary observations may indicate that in patients with relatively lower inflammation, aspirin prophylaxis could be less effective, potentially favoring VTE onset. In two VTE cases, cytokine profiling showed decreased M-CSF, SCLF-β, and MIP-1α, with increased G-CSF, raising the hypothesis of distinct immune-inflammatory pathways contributing to TEs. Given the limited number of patients and thrombotic events, and the cytokine data available for only two VTE cases, these associations should be regarded as exploratory and interpreted with caution. Overall, these exploratory findings warrant validation in larger, independent cohorts and may help generate hypotheses on how inflammatory signatures influence thrombotic risk and prophylaxis efficacy in MM patients receiving IMiD/anti-CD38-based regimens. Full article

Background: The main type of treatment of unresectable NSCLC is chemoradiotherapy, which has a relatively high toxicity. One option allowing to reduce the toxicity of this approach may be immunocorrective therapy. The appointment of this type of treatment should be warranted in terms of patient’s immune system response. This confirms the importance of verifying systemic immune disorders in primary patients with NSCLC. Goal: To assess the features of the population of immune cells in peripheral blood in patients with stage IIIB, IIIC primary NSCLC and to identify any signs of secondary immunodeficiency in this cohort. Methods: We analyzed the frequencies of circulating T cells (CD3+, CD4+, CD8+), B-cells (CD19+), NK-cells (CD3-CD16+CD56+ cell), and NKT-cells (CD3+CD56+ cells) within CD45+ cells (lymphocytes) in 80 patients with stage IIIB-IIIC NSCLC, and in 40 healthy controls using eight-color flow cytometry. Results: In patients with stages IIIB-IIIC primary NSCLC, changes within immunocompetent blood cells were found. Moreover, it was unveiled that quantitative changes affected all major immunocompetent cells. A decrease in the proportion of CD4+ T cells and B lymphocytes and an increase in the number of NK and NKT cells were found. Also, an increase in the number of double-positive CD4+CD8+ T cells was revealed, as well as a significant increase in the proportion of B1a (CD5+CD19+) cells among B lymphocytes (qualitative disorders). Conclusion: The revealed multidirectional changes among immunocompetent peripheral blood cells in patients with locally advanced NSCLC (stages IIIB-IIIC) can be beyond doubt considered as signs of systemic immune disorders in this cohort (secondary immunodeficiency). Full article

Concurrent occurrence of two independent primary malignancies in a single dog is rare and presents diagnostic and surgical challenges. A 9-year-old neutered male Cocker Spaniel was diagnosed with adrenal pheochromocytoma and splenic diffuse large B-cell lymphoma. Abdominal imaging revealed two distinct masses. Surgical management included adrenalectomy, splenectomy, mesenteric lymphadenectomy, and excision of a small mass adherent to the portal vein adventitia. Histopathology confirmed two separate malignancies, with chromogranin A positivity supporting pheochromocytoma and CD20 positivity confirming B-cell lymphoma. No additional metastatic lesions were identified, and the portal vein-associated mass was considered an isolated lesion closely adherent to the vessel wall, with its exact pathogenesis remaining uncertain. To the authors’ knowledge, this represents the first veterinary report describing adrenal pheochromocytoma with portal vein involvement successfully managed by surgical removal. The patient recovered well and remained disease-free for three years without adjuvant therapy. This case emphasizes that, even in technically demanding situations, meticulous surgical planning and comprehensive oncologic assessment can achieve durable remission and inform future approaches to complex veterinary cancers. Full article