Flow cytometry is the cornerstone for establishing the diagnosis of chronic lymphocytic leukemia (CLL), owing to its characteristic and well-defined immunophenotype that enables accurate distinction from other leukemias and lymphomas. Beyond diagnosis, flow cytometry provides essential prognostic information and allows sensitive detection of minimal residual disease (MRD), a strong predictor of clinical outcome. CLL MRD assessment is increasingly used to guide risk stratification, therapeutic decision-making, and treatment duration in the era of targeted therapies and immunotherapies. This chapter reviews best practices for specimen collection, processing, staining, and data analysis and summarizes the principles of flow cytometric MRD assessment in CLL.

Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality worldwide. FOLFOXIRI combined with targeted agents has shown promising outcomes in mCRC. This meta-analysis compares efficacy and safety of FOLFOXIRI plus cetuximab versus FOLFOXIRI plus bevacizumab in patients with mCRC.

A literature search was conducted across PubMed, Cochrane, Embase, Scopus, and clinicaltrials.gov until February 2025. Analysis was performed using RStudio v4.5.0. Pooled estimates are reported as hazard ratios, odds ratios, risk ratios, and mean difference with 95% CIs using random-effects model. Heterogeneity was assessed using I² statistics.

Four studies (3 RCTs, 1 observational) comprising 561 patients were included. Overall survival did not differ significantly between FOLFOXIRI-cetuximab and FOLFOXIRI-bevacizumab (HR: 1.22; 95% CI: 0.78 - 1.90; p = 0.386). Progression-free survival also did not differ significantly (HR: 1.32; 95% CI: 0.76-2.31; p = 0.324). Objective response rate, complete response, and partial response did not differ significantly [(OR: 1.48; 95% CI: 0.50-4.37; p = 0.4772), (OR: 1.59; 95% CI: 0.66-3.86; p = 0.303), and (OR: 1.60; 95% CI: 0.52-4.93, p = 0.414) respectively]. Depth of response showed no significant difference (MD: 15.29; 95% CI: -1.35-31.94; p = 0.07). Hypomagnesemia and acneiform rash were significantly more frequent with cetuximab (p < 0.01). However, alopecia, anemia, neurotoxicity, and all-grade stomatitis showed no difference between the two arms.

FOLFOXIRI-cetuximab did not improve PFS, OS, or response rates in patients with mCRC compared with the bevacizumab combination; however, it was associated with significantly higher rates of hypomagnesemia and acneiform rash.

Poor penetration into tumor tissue remains a major barrier to effective nanomedicine delivery, particularly in glioblastoma multiforme (GBM). Here, nanoparticle transport was computationally studied to rationally design an ultrasmall chemotactic nanomotor that improves penetration into dense tumor tissue. The nanomotor comprises a targeting human heavy-chain ferritin (HFn) nanocage and a catalytic cerium oxide (CeO₂) component. Leveraging transferrin receptor‑1 overexpression on brain microvascular endothelial cells and GBM cells, HFn enables transport across an in vitro blood-brain barrier (BBB) model and accumulation in GBM spheroids. The CeO₂ domain catalyzes hydrogen peroxide decomposition in the tumor‑mimicking microenvironment, generating oxygen and imparting directional propulsion along H₂O₂ gradients. In chemotaxis assays, the nanomotors actively migrated toward localized H₂O₂ sources and GBM cells embedded in Matrigel. In large U87 spheroids (>400 µm), HFn@CeO₂ nanomotors penetrated deeply and distributed throughout the spheroid core, whereas non‑propelled HFn nanocarriers remained confined mainly to the periphery. Doxorubicin‑loaded nanomotors (HFn@CeO_2-DOX) achieved substantially enhanced intratumoral DOX distribution and reduced IC₅₀ (0.33 µM) compared with HFn-DOX (1.13 µM) and free DOX (1.75 µM) in GBM spheroids. These results provide a promising basis for future in vivo evaluation in brain tumor therapy.

To analyse the use of opioids in children with cancer and the experiences of their family members regarding opioids used in pain management to improve family nursing.

An integrative review.

A systematic literature search was carried out in four databases (CINAHL, MEDLINE, PsycInfo and Scopus) in August 2023, and was subsequently updated to include studies up to the end of 2024. Sixteen peer-reviewed research articles met the inclusion criteria and were included in a quality appraisal and analysis.

Of the wide range of opioids used to treat pain in children with cancer, morphine and fentanyl stood out as the most used. The prevalent routes of opioid administration was intravenous and enteral. Limited research has been conducted on the experiences of family members of children with cancer in the context of opioids used for pain management. Furthermore, there is a scarcity of studies that describe the experiences of siblings from the same perspective. Parental experiences were particularly described as concerns about and a desire to refuse opioid use, although satisfaction with opioid use was also described.

Opioids are particularly significant in managing pain among children with cancer. Therefore, the use of opioids in this patient group should be comprehensively studied, and healthcare professionals should receive sufficient training. The experiences of parents conclude that they require sufficient information and guidance on the management of their children's severe pain and the analgesics used to treat it. The notable lack of research regarding the experiences of siblings in connection with the use of opioids for the management of a child's pain addresses the need for further research from these perspectives. More research on experiences during the different phases of cancer treatment is needed. Further research employing qualitative methods will be essential for enhancing family nursing.

Splenogonadal fusion (SGF) remains one of the rarest and most diagnostically deceptive causes of scrotal pathology, frequently mimicking the clinical and imaging features of testicular malignancy despite its benign histology. Its exceptional rarity in adults, combined with the absence of reliable noninvasive preoperative diagnostic criteria, creates a major challenge in urologic practice, often necessitating management driven by concern for cancer. We present a 29-year-old man with a symptomatic left testicular mass and imaging highly suspicious for malignancy, prompting radical inguinal orchiectomy after standard evaluation could not confidently exclude a testicular neoplasm. Unexpectedly, final histopathology demonstrated ectopic splenic tissue consistent with SGF without evidence of germ cell tumour or other malignancy. This case highlights the persistent gap between preoperative suspicion and definitive diagnosis, emphasizing the importance of recognizing rare benign entities that closely imitate testicular cancer and may still lead to radical surgery in otherwise healthy young adults unnecessarily.

Clear cell renal cell carcinoma (ccRCC) is the most common histological subtype of malignant renal neoplasms, with an increasing incidence in Western countries. Early diagnosis is a critical determinant of prognosis, as advanced-stage disease with metastatic dissemination entails a significantly reduced median survival. Characterizing complex cystic renal lesions presents a recognized diagnostic challenge on noncontrast computed tomography (CT), which often leads to underestimation and missed diagnoses. Artificial intelligence (AI) applied to diagnostic imaging is emerging as a supplementary decision-support tool, but its integration must be critically evaluated to understand its potential to reduce diagnostic errors as well as its limitations.

We report the case of a 73-year-old male physician with a history of myocardial infarction who presented with left flank pain. An initial noncontrast CT of the urinary tract on January 15 revealed a 37-mm left upper-pole renal cyst and a 5-mm suspected calculus. The cyst was characterized as simple, and the report offered only a generic follow-up recommendation. Over the next 4 months, the patient's persistent pain was attributed entirely to presumed ureteric stone disease, leading to a ureteroscopy and ureteral stent placement, without characterizing the known renal cyst with contrast. On June 5 (5 months after the initial CT), a contrast-enhanced CT revealed a 6-cm heterogeneous, exophytic left renal mass. Subsequent staging confirmed pulmonary and cerebral metastases from ccRCC. The patient died in mid-August, 7 months after the initial CT. Retrospective re-evaluation of the baseline CT images, both by a senior radiologist and through an AI platform, confirmed that the lesion already exhibited features suspicious for neoplasia at the time of the first scan, warranting further investigation with contrast-enhanced CT or magnetic resonance imaging in accordance with international guidelines. Simulated retrospective analysis via a web-based AI platform not only flagged the mass as suspicious but also generated several critical errors (e.g., hallucinating contrast enhancement on the unenhanced scan, mislocalizing the mass to the mid-to-lower pole, and claiming it was "new" without comparison data).

This case demonstrates how a complex cystic renal lesion may be underestimated in the absence of contrast medium and an adequate level of clinical-radiological suspicion. Re-evaluation by AI produced a result consistent with that of the expert radiologist, suggesting that systematic integration of AI tools into the radiological workflow could contribute to reducing diagnostic errors, particularly in settings where interobserver variability represents a clinically significant risk factor. AI can act as an effective supplementary decision-support tool to reduce perceptual errors; clinicians and radiologists must remain highly vigilant regarding AI-generated factual inconsistencies. Proper adherence to imaging guidelines and the use of contrast medium remain paramount.

Cutaneous melanoma is an aggressive malignancy characterized by a high metastatic potential and variable response to immune checkpoint blockade (ICB). The extracellular matrix protein proline/arginine-rich end leucine-rich repeat protein (PRELP), an extracellular matrix protein, contributes to stromal architecture and tumor-immune interactions. This study investigated whether PRELP expression drives transcriptomic remodeling, alternative splicing, interferon (IFN)-related signaling pathways to influence immunotherapy responsiveness in melanoma.

Bulk RNA sequencing was performed on PRELP-high and PRELP-low BUF1088 melanoma cells to assess differential gene expression and alternative splicing landscapes. Downstream pathway changes were characterized using hallmark enrichment analysis. The translational relevance of the profiles was assessed using publicly available single-cell RNA sequencing datasets and clinical melanoma ICB cohorts.

Differential splicing analysis identified 274 significant splicing events across 230 genes, predominantly exon skipping events. Key differentially spliced genes included AAR2, SACM1L, CD22, ACTB, MYO5A, WARS1, BTN3A3, IL24, and HNRNPA3. In parallel, PRELP-high melanoma cells showed enrichment of IFN-gamma and IFN-alpha response pathways accompanied by increased expression of IFI27, IFI44, IRF7, and IFITM3. In publicly available clinical datasets, PRELP expression and a composite PRELP-related gene signature, (PRELP, IRF7, IFI27, IFI27L1, IFI44, IFITM3, WARS, and IL24) were significantly enriched in ICB responders versus non-responders. Single-cell mapping localized endogenous PRELP expression to specific stromal subsets, primarily extracellular matrix-remodeling myofibroblastic CAFs (myCAFs) and IFN-responsive CAFs.

These findings demonstrate that PRELP expression in melanoma orchestrates extensive transcriptomic remodeling, linking stromal matrix programs with IFN-associated antitumor signaling and alternative splicing landscapes. Consequently, PRELP-associated expression and splicing signatures represent promising predictive biomarkers to guide patient selection for immunotherapy response.

As the stable and conserved circular non-coding RNAs, circular RNAs (circRNAs) have assumed growing significance in regulating breast cancer immunity and immunotherapy. This review focuses on elucidating the molecular mechanisms through which circRNAs influence the efficacy of breast cancer immunotherapy. Specifically, circRNAs modulate the levels and stability of critical immune checkpoints, including PD-L1 and various cytokines. They achieve this by acting as competing endogenous RNAs (ceRNAs) to sequester miRNAs, functioning as protein scaffolds, and thereby modulating gene expression and tumor immune evasion. Furthermore, circRNAs are capable of facilitating communication between tumor cells and immune cells. In addition, it can be translated into proteins that aid in remodeling the tumor immune microenvironment. These changes may include driving the polarization of immunosuppressive M2-type macrophages, while suppressing the infiltration and functional activity of cytotoxic T cells and natural killer cells. These findings highlight the significant promise of circRNAs serving as novel biomarkers and candidate therapeutic targets. Targeting specific circRNAs is anticipated to emerge as an effective approach for enhancing the efficacy of current immune checkpoint inhibitors, potentially helping to overcome drug resistance encountered in immunotherapy. Furthermore, it offers potential for the development of novel circRNA-based vaccines. Collectively, these advancements pave the way for improving the prognosis of breast cancer immunotherapy and open new avenues for future research and clinical translation.

Adrenocortical carcinoma (ACC) is a rare malignancy, accounting for 0.05-2% of all malignant tumors. Most cases are sporadic and asymptomatic, often discovered incidentally via imaging. However, 50-60% present with autonomous hormonal secretion, with 45% producing excess cortisol, and only 1% exhibiting mineralocorticoid excess. We report a 43-year-old Filipino female with a 6-month history of abdominal bloating, proximal muscle weakness, edema, and hypertension. Laboratory tests showed hypokalemia (serum potassium 2.5-3.05 mmol/L; normal 3.3-5.0 mmol/L). Imaging revealed a neoplastic right suprarenal mass (adrenal origin vs confluent lymphadenopathy) described as an incidental, lipid-poor right adrenal mass measuring 4.7 x 3.6 x 6.1 cm, with contrast-enhanced Hounsfield units of 40, along with periportal and paraaortic lymphadenopathies. Biochemical evaluation indicated an intermediate probability of primary aldosteronism: suppressed plasma renin at 0.97 ug/L/hr (0.97 ng/mL/hr), normal plasma aldosterone 599.46 pmol/L (21.61 ng/dl), and aldosterone-renin ratio of 618 (pmol/L)/(ng/L/hr) (22.27 ng/dl/ng/mL/hr). Ideally, confirmatory testing with an aldosterone suppression test prior to imaging and adrenal vein sampling (AVS) should be performed to lateralize the lesion before surgery; however, the patient opted to proceed with surgery. The patient also had overt hypercortisolism, with non-suppressed serum cortisol of 31.88 µg/dL (reference <1.8 µg/dL) on a low-dose dexamethasone suppression test, suppressed ACTH at 2.81 pg/mL (reference 7.7-63.6 pg/mL) (Table 1), and clinical features of Cushing syndrome, including facial plethora, and proximal muscle weakness. While these findings support the diagnosis of an ACTH-independent hypercortisolism, current guidelines recommend confirmatory testing, including 24-hour urinary free cortisol or late-night salivary cortisol, before definitive evaluation to distinguish ACTH-dependent from ACTH-independent disease. Concomitant catecholamine and androgen excess were excluded with normal 24-hour urine metanephrines and serum DHEAS. Surgical removal via open adrenalectomy was performed. Histopathology confirmed ACC, supported by immunohistochemistry. Postoperative treatment included radiotherapy and planned adjuvant mitotane therapy. During follow-up, the patient's blood glucose and blood pressure worsened, requiring medication adjustments. Unfortunately, the patient succumbed to the disease seven months post-surgery. This case highlights the difficulties in assessing adrenal tumors that concurrently secrete cortisol and aldosterone, especially when biochemical results are inconclusive, emphasizing the need for careful assessment and prompt intervention in this rare coexistence.

Multiple myeloma (MM) is an incurable malignancy and ranks as the second most common hematological cancer in western countries. Relapsed disease is common in MM patients, and is largely influenced by the establishment of an immunosuppressive tumor microenvironment (TME) and concomitant systemic immune impairment. Myeloid-derived suppressor cells (MDSCs) are crucial regulators of immune homeostasis and response in various pathological states, including cancer. Within the TME, MDSCs and tumor cells engage in bidirectional crosstalk through both direct and indirect mechanisms, collectively driving immune evasion and tumor progression. As a principal immunosuppressive population within the MM milieu, MDSCs play a central role in the immunoregulation of MM. Although immunotherapy has emerged as a pivotal treatment modality for MM, MDSCs, the key constituents of the TME, constitute a major source of resistance to such therapies. This review elucidates the mechanisms governing MDSCs interactions within the myeloma TME, discusses potential therapeutic strategies targeting MDSCs, and outlines a rational framework for integrating MDSC-directed approaches with current MM therapies and immunotherapy.