Pituitary adenomas (PAs) are common brain tumors, accounting for about 15% of all brain neoplasms. Although generally benign, they can lead to serious complications through mass effects and hormone dysregulation. Emerging evidence suggests that collagen, a major component of the extracellular matrix (ECM), plays a pivotal role in PA pathophysiology. Collagen provides both structural integrity and biochemical cues within the tumor microenvironment (TME), influencing cellular behaviors and intercellular interactions. Recent studies indicate that collagen remodeling in PAs is dynamic, with alterations in collagen composition and organization affecting tumor growth, invasion, and hormone secretion. Collagen degradation products and collagenase activity may also facilitate tumor invasion into adjacent tissues. Additionally, collagen has been implicated in immune modulation, acting as a physical barrier that restricts immune cell infiltration and promotes immune evasion through receptor-mediated signaling. Metabolically, collagen may serve as an energy source or modulate metabolic pathways to sustain tumor proliferation. Clinically, collagen content in PAs correlates with tumor consistency, which has implications for surgical resection strategies. Moreover, serum collagen is emerging as a potential non-invasive biomarker for PA diagnosis and prognosis. Targeting collagen synthesis, degradation, or its mechanotransductive signaling pathways represents a promising therapeutic avenue.

Recent advances in bladder cancer immunotherapy have shown promise, particularly in addressing limitations of the current gold standard, Bacillus Calmette-Guérin (BCG). Novel combinations, such as sasanlimab (a PD-1 monoclonal antibody) with BCG, have improved event-free survival in high-risk non-muscle-invasive bladder cancer (NMIBC). Intravesical anti-PD-1/PD-L1 agents like pembrolizumab and nadofaragene firadenovec have demonstrated efficacy and safety in BCG-unresponsive NMIBC, leading to regulatory approval. Additionally, BCG combined with immunostimulatory protein complexes (e.g., N-803) achieved high complete response rates while preserving quality of life. For muscle-invasive bladder cancer (MIBC) patients ineligible for cisplatin, neoadjuvant immunotherapy trials are exploring anti-PD-1/PD-L1 monotherapy or combinations with anti-CTLA-4 antibodies. The Pandore trial highlights the role of mucosal immunity in predicting response to systemic immune checkpoint inhibitors. Promising results have also been observed with intravesical oncolytic immunotherapy combined with systemic anti-PD-1 therapy in cisplatin-ineligible MIBC. These advancements underscore the potential of intravesical and systemic immunotherapies to improve bladder cancer outcomes and warrant further investigation.

Somatostatin analogues (SSA) are used in the management of patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET) to control hormone secretion and tumour growth. SSA can paradoxically worsen or unmask hypoglycaemia in patients with insulinoma by inhibiting counter-regulatory hormones such as glucagon and growth hormone.

We present two cases of SSA use in patients with initially presumed non-functioning GEP-NET unmasking insulinoma. We review the use of SSA in GEP-NET and the management of refractory hypoglycaemia in metastatic insulinoma.

A 62-year-old female with metastatic grade 2 GEP-NET was commenced on monthly lanreotide 10 weeks after diagnosis. She presented 1 week following the second dose with refractory hypoglycaemia and inappropriate hyperinsulinism, requiring inpatient dextrose infusion. SSA was stopped; however, she remained dextrose dependent despite the addition of diazoxide and dexamethasone. Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTA-Octreotate was given, resulting in resolution of hypoglycaemia after two cycles. The second case is a 57-year-old female with metastatic grade 2 GEP-NET. Four months post commencement of lanreotide, she presented with radiological disease progression and symptomatic hypoglycaemia. A 72 h fast confirmed hyperinsulinaemic hypoglycaemia. SSA was stopped. A trial of diazoxide was not tolerated, and a prednisolone trial was ineffective. The patient underwent inpatient PRRT with euglycaemia achieved shortly afterwards.

SSA can unmask hypoglycaemia secondary to insulinoma. Detection of new-onset hypoglycaemia requires careful clinical vigilance when commencing SSA in patients with GEP-NET initially presumed to be non-functional. Hypoglycaemia from metastatic insulinoma requires multidisciplinary management incorporating nutritional, medical and oncologic therapy. PRRT can be effective in managing refractory hypoglycaemia.

SSA use can unmask insulinoma in a NET presumed to be non-functional.SSA can paradoxically worsen hypoglycaemia in insulinoma due to suppression of counter-regulatory hormones.There are currently no biomarkers in routine clinical use to predict which patients will experience a worsening of hypoglycaemia after SSA initiation. Detection of new-onset hypoglycaemia requires clinical vigilance and education of patients to report symptoms early to enable prompt investigation and management.Symptomatic hypoglycaemia in metastatic insulinoma is challenging to manage and requires a multidisciplinary approach considering diet, medical therapy and urgent initiation or escalation of oncologic therapy.PRRT is a safe and effective strategy to achieve hormonal and oncologic control in metastatic insulinoma. Caution should be practised regarding flare of insulin release, and inpatient administration with expert endocrinology, nuclear medicine and oncology input should be considered.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has a low malignancy potential. First acknowledged by the WHO in 2017, this tumor is rare in the pediatric population, with less than 25 cases reported. Accurate diagnosis is key to avoid overtreatment and complications.

Two cases of adolescents with solid thyroid nodules assessed by fine-needle aspiration biopsy are presented. Hemithyroidectomy was decided upon. Both surgical specimens were reported as NIFTP. Both cases were presented before a cross-disciplinary board, and since malignancy potential was low, treatment was regarded as completed.

NIFTP identification is key to avoid unnecessary treatments such as total thyroidectomy or iodine therapy, which may bring about serious consequences in children. A high level of diagnostic suspicion and a cross-disciplinary approach are required to optimize management and clinical results in these patients.

Ovarian cancer (OC), one of the most common gynecological cancers, is usually diagnosed at an advanced stage. High-grade serous ovarian cancer (HGSOC) is a histological subtype of OC that accounts for approximately 70% of all OC cases. erb-b2 receptor tyrosine kinase 2 (ERBB2) overexpression commonly occurs in HGSOC, accounting for 12.5% of stage III and IV HGSOCs. Currently, there is no established treatment strategy for OC patients with ERBB2 amplification or ERBB2 overexpression. Whether these patients will benefit from ERBB2 inhibitors remains unclear. Herein, we report a patient with metastatic HGSOC carrying ERBB2 amplification and ERBB2 overexpression. Following progression to platinum-based chemotherapy and subsequent antiangiogenic therapies, the patient benefited from late-line pyrotinib treatment, achieving stable disease with a progression-free survival of 9.5 months. Our study provides preliminary clinical evidence supporting pyrotinib as a feasible treatment option for metastatic HGSOC patients with ERBB2 amplification and/or ERBB2 overexpression. Prospective trials of pyrotinib should be conducted in appropriately selected OC populations.

To conduct an economic evaluation of a group mindfulness program compared to an education support program for breast cancer survivors (BCS).

The cost-utility analysis (cost per quality-adjusted life year [QALY]) was performed from a single-center randomized controlled trial in the United States. Data from 181 BCS were included in the analysis (91 from the mindfulness-based stress reduction for breast cancer, MBSR(BC) and 90 from the Breast Cancer Education Support, (BCES)). Analyses were conducted from two perspectives: societal and healthcare system. The EuroQol EQ-5D-5L was used to measure quality of life and the Client Service Receipt Inventory (CSRI) was used to measure health services utilization from baseline through 26 weeks. The impact of MBSR(BC) on health services utilization and costs was estimated with generalized linear models.

In the reference case analyses (societal perspective), the average total cost in the MBSR(BC) group was $5744 compared with $6140 in the BCES group. At the end of follow-up, the MBSR(BC) group dominated BCES in terms of Incremental Cost Utility Ratio (ICUR), with MBSR(BC) providing an incremental cost of -$541 (95% CI: -$3400, $2318) and a 0.021 QALY (95% CI: -0.014, 0.055). Net monetary benefit (NMB) analysis showed that MBSR(BC) has a higher probability of achieving positive NMB across a range of possible societal willingness-to-pay for improving quality of life.

Our findings suggest that MBSR(BC) is likely to be cost-effective for breast cancer survivors over 6 months. Cost savings primarily resulted from reduced ER and hospital admissions and tests.

The concurrent use of a ropivacaine transversus abdominis plane (TAP) block with intravenous lidocaine infusion, though effective for pain relief, raises safety concerns regarding local anesthetic systemic toxicity (LAST). This study aimed to assess the dose-risk relationship of LAST in this combination by escalating the ropivacaine dose while fixing the lidocaine dose.

In this dose-escalation study, adult patients undergoing colorectal cancer surgery received a 0.2% ropivacaine TAP block (1.5, 2.0 or 2.5 mg kg^-1) and intravenous lidocaine infusion (2 mg kg^-1 bolus, followed by 2 mg kg^-1 h^-1), both dosed according to ideal body weight (IBW). The primary outcome was the occurrence of LAST, identified by clinical symptoms, new-onset ECG irregularities, etc. Secondary outcomes included plasma concentrations of ropivacaine and lidocaine.

Nine patients were included in the per-protocol analysis, and 26 were included in the intention-to-treat analysis. No signs of LAST were observed. Plasma ropivacaine concentrations remained consistently below 2.2 µg mL^-1, however, eight patients in the intention-to-treat population and three patients in the per-protocol population had plasma lidocaine concentrations exceeding 5.0 µg mL^-1 at 10 min post-bolus. In the per-protocol population, peak plasma ropivacaine concentrations occurred at 30 min (range, 20-60) post-TAP block, with median values of 1.14 (range, 0.85-1.18), 1.42 (range, 1.29-1.80), and 1.96 (range, 1.47-2.06) µg mL^-1 across dose groups. The peak plasma lidocaine concentrations in patients occurred at 10 min post-bolus infusion, with median values of 4.59 µg mL^-1 (range, 3.24-6.67) and gradually decreased after 2 h. The intention-to-treat analysis found similar results.

Although no signs of LAST were observed with the combination of a 1.5 to 2.5 mg kg^-1 ropivacaine TAP block and intravenous lidocaine infusion under general anaesthesia, extreme caution is still warranted regarding the potential risk of LAST.

This trial was registered at ClinicalTrials.gov (NCT06006026) on 23 August 2023.

Cancer is a leading cause of mortality worldwide, with approximately 19.6 million new cases and 10 million deaths reported in 2020. Exercise interventions have demonstrated positive effects on physical and mental health in cancer patients, yet there is limited evidence on the efficacy of tailored, high-intensity exercise programs designed using genomic data. This protocol outlines a study aimed at integrating genomic analysis and personalized exercise interventions to improve health outcomes and reduce cancer-related risk factors. This study aims to evaluate the feasibility and potential impact of a personalized exercise intervention delivered through the EXESALUS mobile application. The program integrates genomic information to tailor exercise regimens for cancer prevention, muscle strength improvement, and quality-of-life enhancement.

This is a protocol for a 3-month, parallel-group, randomized controlled trial involving 500 participants, including 100 cancer patients undergoing treatment or rehabilitation and 300 non-cancer participants with elevated disease risk. Participants will engage in the EXESALUS program, which includes low-, moderate-, and high-intensity exercise tailored to genomic profiles, supported by exercise counseling and wearable device feedback. Biospecimens (blood, urine, and oral epithelial cells) will be collected at baseline, 6 weeks, and 3 months to assess genomic variations and physiological changes. Primary outcomes include physical performance (SPPB), muscle strength (1RM and peak power), and skeletal muscle mass (DXA). Secondary outcomes will evaluate mental health indicators such as fatigue (FACIT-F), resilience, anxiety, depression, and quality of life.

This study will provide a detailed framework for implementing ICT-based personalized exercise interventions that incorporate genomic analysis. The EXESALUS program is expected to highlight the potential of tailored high-intensity exercise as a preventive and therapeutic strategy for cancer patients and individuals at risk of chronic diseases. The findings of this protocol will contribute to the development of precision medicine approaches for cancer prevention and management, emphasizing the scalability and utility of ICT-based solutions in health promotion.

This study was registered in the Korean Clinical Trials Registry (KCT0010187).

Yes-associated protein (YAP) is a core component of the Hippo pathway, which functions as an oncogene in various cancers. However, emerging evidence has shown that YAP can also act as a tumor suppressor. Therefore, understanding the function and molecular mechanism of YAP is crucial for developing YAP-targeted drugs in tumors.

A comprehensive literature review was conducted. The review mainly includes the post-translational modification, the regulatory mechanisms and function of YAP in esophageal squamous cell carcinoma (ESCC).

YAP undergoes various post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation and others, which critically regulate its protein stability and transcriptional activity in multiple tumors, particularly ESCC. YAP is highly expressed in ESCC tissues, with its aberrant activation closely correlated with poor prognosis in patients. Additionally, YAP is involved in the progression of ESCC, including tumor migration, invasion, proliferation, cell stemness, apoptosis, therapeutic resistance, and immunity. In ESCC, YAP has been confirmed to be regulated by multiple upstream regulators, such as E3 ubiquitin ligases and kinases, thereby influencing the ESCC progression. However, there are still few drugs available clinically for YAP-targeted therapy, which requires further research. In this review, we systematically synthesize the biological roles and regulatory mechanisms of YAP in ESCC and outline potential research directions for YAP-targeted therapies, aiming to provide novel insights for precision medicine in ESCC.

YAP is closely correlated to ESCC progression, and it could be a promising target for ESCC treatment.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive blood cancer from plasmacytoid dendritic cell precursors. It's marked by CD4, CD56, CD123, and CD303/CD304 expression and involves molecular disruptions like chromatin deletions, mutations, and chromosomal translocations.

The current study employed a comprehensive method with clinical samples, histology, FACS immunophenotyping, karyotype analysis, transcriptome and protein structure analysis, and single-cell sequencing to explore BPDCN's molecular basis.

The study discovered a new MYB-ZFAT gene fusion in a BPDCN patient and showed a diverse cell population, contradicting a single cell type theory. It found four major clusters (Cluster 1,2,3,8 ) and one cluster (clulster 12) with unique profiles and roles in disease progression. The research noted Key pathways include T cell receptor signaling, NK cell cytotoxicity, and hematopoiesis are involved in pathogenesis. The study emphasized MYB activation's role in BPDCN's cellular clustering and identity.

The study indicates BPDCN's complexity with varied cellular origins and a significant role for MYB activation in its development. This research deepens our comprehension of BPDCN's pathogenesis and cell populations.