ABSTRACTBackgroundGastric carcinoma poses a significant global health challenge, often diagnosed late due to its similarity to chronic gastric conditions. Helicobacter pylori (Hp) infection plays a crucial role in gastric carcinogenesis through inflammation and the release of virulent products.AimThis study aimed to identify Hp infection‐related genes associated with gastric cancer prognosis and to develop a prognostic risk model that can predict patient outcomes, characterize the tumor immune microenvironment, and evaluate potential responses to immunotherapy.Methods and ResultsIn this study, multiple GEO datasets with Hp infection were analyzed to identify genes associated with gastric cancer prognosis. A predictive risk scoring model comprising nine genes related to Hp infection and gastric cancer prognosis was constructed and validated. The prognostic model demonstrated its efficacy in predicting prognosis, correlating with clinical characteristics, functional enrichment, immune cell infiltration, genomic mutations, and immune regulator expression. Additionally, analysis of immune therapy response suggested the potential prognostic effect of markers in gastric cancer immune response.ConclusionsThese findings offer valuable insights into gastric cancer diagnosis and targeted therapy, paving the way for improved patient outcomes.

ABSTRACTBackgroundLenvatinib‐related hypothyroidism occurs in 16%–22% of patients with hepatocellular carcinoma and may affect treatment management. Previous studies have reported elevated serum thyroid stimulating hormone (TSH) levels despite levothyroxine therapy, indicating the need for research on the optimal levothyroxine dose during lenvatinib therapy.AimsWe aimed to explore the effect of lenvatinib on thyroid function, focusing on lenvatinib pharmacokinetics and factors influencing hypothyroidism development.Methods and ResultsA retrospective cohort study involving 56 patients with hepatocellular carcinoma treated with lenvatinib was conducted at the Mie University Hospital. The primary outcome was grade ≥ 2 hypothyroidism. Demographic data, treatment details, and clinical outcomes were analyzed to identify factors associated with lenvatinib‐related hypothyroidism. In addition, we assessed the levothyroxine dose administered during treatment and the dose required to achieve TSH levels < 10 mIU/L. Twelve patients (21%) developed hypothyroidism during lenvatinib therapy. The median levothyroxine dose and time to onset of hypothyroidism were 25.0 [25.0–50.0] μg/day and 81.0 [15.0–208.0] days, respectively. Levothyroxine therapy was initiated at either a low or recommended dose, with 10 patients achieving TSH levels < 10 mIU/L. Significant predictors of hypothyroidism included age ≤ 63 years and a higher daily lenvatinib dose (≥ 0.152 mg/kg/day).ConclusionInitiation of levothyroxine therapy, even at lower doses, may be effective in managing lenvatinib‐related hypothyroidism. Underweight patients (e.g., body weight < 50 kg) require particular attention due to their increased susceptibility to hypothyroidism. Even though this study has limitations such as a small sample size and the lack of multivariate analysis, it provides valuable information for managing lenvatinib‐related hypothyroidism.

ABSTRACTIntroductionMultiple myeloma is a common malignant tumor of the hematologic system, and genetic alterations play a crucial role in its occurrence and development. Ferroptosis is an oxidative and iron‐dependent programmed cell death, which has a strong correlation with tumor development. This study aimed to identify potential diagnostic ferroptosis‐related genes of MM.MethodsMM datasets were screened from the GEO database using publicly available transcriptomic data. Ferroptosis‐related hub genes were identified through enrichment analysis, WGCNA, and machine learning algorithms. ROC curves, boxplots, RT‐qPCR, and ELISA were conducted to validate the expression levels of these hub genes.ResultsA total of 178 ferroptosis‐related DEGs were identified, including 114 up‐regulated genes and 64 down‐regulated genes. Enrichment analysis indicated that the DEGs were primarily associated with stress, autophagy, and metabolism. According to the WGCNA, the brown module has the highest correlation with clinical symptoms, containing 1141 DEGs. Combining with the identified ferroptosis‐related DEGs, two hub genes of CDKN1A and BCAT2 were identified by multiple bioinformatics techniques of LASSO, SVM, and Random Forest. ROC curves demonstrated strong diagnostic values in CDKN1A (test set, AUC = 0.881; validation set, AUC = 0.705) and BCAT2 (test set, AUC = 0.808; validation set, AUC = 0.756). RT‐qPCR confirmed that the mRNA expression levels of CDKN1A and BCAT2 in three MM cells (RPMI 8226, WT‐U266, and LP‐1) were both significantly higher than the control HMy2.CIR cell line (p < 0.05). ELISA quantification revealed significantly elevated relative expression of CDKN1A protein in the MM cohort compared to healthy controls (p < 0.01), but the protein expression of BCAT2 exhibited comparable levels (p > 0.05).ConclusionOur results suggest that CDKN1A and BCAT2 are potential ferroptosis‐related biomarkers for MM. This may help understand the molecular mechanisms and therapeutic strategies of MM.

ABSTRACTBackgroundNeuroblastoma (NB) is a childhood cancer of the sympathetic nervous system, and its prognosis is poor. NB cells undergo transcriptional changes to utilise aerobic glycolysis as their primary metabolic pathway, which provides an immediate source of ATP to meet high biosynthetic demands. Alternative metabolic fuel inputs, including ketone bodies which require oxidative phosphorylation, may impact the proliferative capacity of NB.AimsIn this exploratory study, the expression of glycolytic and ketolytic genes in the context of MYCN oncogene amplification, tumour staging 1–4 and Kaplan–Meier survivability was investigated using the R2: Genomics analysis and visualisation platform (http://r2.amc.nl), database.Methods and ResultsThree NB genomics datasets were assessed in the R2 platform and further analysed in GraphPad Prism to investigate the relationships between glycolytic and ketolytic gene expression and prognosis. Glycolytic gene expression is increased in MYCN amplified, metastatic tumours and is associated with worse event free survival. Ketolytic gene expression is lower in metastatic tumours and is associated with better event free survivability. The glycolytic gene expression profile of NB suggests that elevated levels correlate with a low probability of survival. Ketolytic gene expression patterns suggest a decreased reliance for ketolytic energy, which may be exploited to slow tumourigenic growth.ConclusionsThis study validates glycolytic and ketolytic gene expression profiles in metastatic and MYCN amplified NB tumours and through conditional analysis suggests the potential use of these genes in prognosis prediction. Furthermore, the study highlights the reliability and utility of genomic databases as oncogenomic tools for NB research.

ABSTRACTBackgroundOcular adnexal (OA) metastasis from renal cell carcinoma (RCC) is a very rare end‐stage entity with a poor prognosis. Reported here is a case of metastatic RCC for which combination therapy with lenvatinib plus pembrolizumab was given for OA metastasis and achieved an excellent response.CaseA 54‐year‐old man was referred to our hospital complaining of right eye pain, with a right intraocular tumor showing a maximum diameter of 3 cm subsequently revealed by computed tomography (CT) imaging. Additionally, masses in the right kidney, both lungs, and right iliac bone were noted, while a subsequent percutaneous renal needle biopsy indicated RCC with multiple metastases (cT3aN0M1). Administration of lenvatinib plus pembrolizumab combination therapy was given as first‐line treatment, with rapid improvement of the elevated inflammatory response and anemia noted. Findings obtained 17 months following initiation of therapy showed significant shrinkage of the primary and iliac bone lesions, while the OA and lung metastatic lesions had completely disappeared.ConclusionThese results highlight the potential of lenvatinib plus pembrolizumab combination therapy for the treatment of RCC with OA metastasis, which is generally considered to be an end stage for cancer cases.

ABSTRACTBackgroundCancer of unknown primary (CUP) presents diagnostic and management challenges, particularly when associated with rare subsets such as pelvic squamous cell carcinoma (SCC) of unknown primary origin. Human papillomavirus (HPV) is increasingly recognized as a prognostic and potentially predictive biomarker. HPV‐associated SCCs often demonstrate better response to treatment and improved outcomes.CasesWe present two cases of pelvic SCC with unknown primary origin, both positive for HPV genotype 16. Case 1 involved a 54‐year‐old woman with persistent abdominal pain who was diagnosed with an infiltrative 110 × 100 × 65 mm tumoral mass on the right side of the pelvic cavity, significantly involving the right iliac bone and right iliopsoas muscle; despite chemotherapy, the patient developed metastases. Case 2 featured a 46‐year‐old woman with progressive left lower limb pain, whose pelvic SCC was incidentally discovered on imaging with an 80 × 75 mm mass with an abnormal signal in the left iliac bone with extension to the left iliopsoas muscle involving the lower aspect of the iliopsoas muscle, and also involving the anterior aspect of the left sacral bone. She achieved a complete response to chemotherapy and chemoradiotherapy, with no evidence of recurrence during follow‐up.ConclusionHPV‐associated pelvic SCC of unknown primary presents both diagnostic complexity and therapeutic opportunity. The detection of HPV genotype 16 in both cases supports a growing body of case‐based evidence suggesting a potential association with a favorable prognosis. However, further studies are needed to clarify its role in guiding management.

ABSTRACTBackgroundMycosis fungoides (MF) is a type of cutaneous T‐cell lymphoma (CTCL) with slow progression, usually presenting with patches and plaques. The infiltration of histiocytes and eosinophils in skin cancers can mask the underlying condition, posing a diagnostic challenge. While cases of MF associated with tissue eosinophilia or histiocytosis infiltration resembling Langerhans cell histiocytosis (LCH) have been reported, the simultaneous occurrence of both conditions in a single MF patient has not been documented.CaseIn this case report, we presented an elderly man with a known history of patch and plaque‐stage MF who developed a large cutaneous tumor on his right mandibular margin. Multiple biopsies initially led to misdiagnoses, attributing the lesion to Well's syndrome and LCH due to the dense infiltration of eosinophils and histiocytes, respectively. However, the absence of a BRAF V600 mutation and lack of clinical correlation reduced the likelihood of these initial diagnoses. After repeated biopsies and a thorough evaluation by hematopathology and dermatopathology specialists, the findings were reassessed, leading to the consideration of tumoral MF with reactive eosinophil and histiocyte infiltrates. The patient was subsequently started on chemotherapy and phototherapy, which led to tumor regression after treatment initiation.ConclusionThis case highlights the importance of considering MF in patients presenting with tissue eosinophilia or Langerhans cell infiltration, even when initial biopsies lack definitive features.

ABSTRACTBackgroundNeuroendocrine neoplasms (NENs) constitute a heterogeneous group of rare tumors that most commonly originate from the gastrointestinal tract and lungs, with a consistently rising global incidence over recent decades. Hepatobiliary neuroendocrine neoplasms (HB‐NENs), defined as primary NENs arising in the liver and biliary tract, are exceedingly uncommon, accounting for less than 0.5% of all NENs. Owing to their low incidence, atypical clinical presentations, and the paucity of large‐scale datasets, no distinct World Health Organization (WHO) classification criteria have yet been established for these entities. Epidemiological characteristics and prognostic studies of HB‐NENs remain extremely limited. Current prognostic evaluation relies predominantly on the American Joint Committee on Cancer (AJCC) and European Neuroendocrine Tumor Society (ENETS) TNM staging systems, whereas population‐level investigations into incidence trends, survival determinants, and individualized predictive tools for HB‐NENs are still largely absent.AimsTo investigate epidemiological trends (1992–2020) and prognostic factors associated with overall survival in a nationally representative cohort of patients with hepatobiliary neuroendocrine neoplasms using the Surveillance, Epidemiology, and End Results registry, with subgroup stratification by sex and race. Additionally, we aim to develop a prognostic nomogram integrating significant predictors to quantify individualized survival probabilities for this population.MethodsIn this cohort study, patients diagnosed with hepatobiliary neuroendocrine neoplasms between January 1, 1975, and December 31, 2020, were identified from the Surveillance, Epidemiology, and End Results Program. Related data were used for epidemiologic and survival analysis, as well as the development and validation of a nomogram to predict the overall survival probability of individual hepatobiliary neuroendocrine neoplasms patients.ResultsThe age‐adjusted incidence rate of hepatobiliary neuroendocrine neoplasms increased 1.76‐fold from 1992 to 2020 (annual percentage change [APC], 2.73; 95% CI, 1.86−3.65; p < 0.05). Furthermore, the incidence of hepatobiliary neuroendocrine neoplasms in the extrahepatic bile duct increased most significantly (APC, 3.73; 95% CI, 2.03−5.46; p < 0.05), and the gallbladder also increased most significantly (APC, 3.51; 95% CI, 1.97−5.08; p < 0.05), whereas patients with hepatobiliary neuroendocrine neoplasms in the liver had no significant difference. As for tumor type, the incidence increased in hepatobiliary neuroendocrine carcinomas (APC, 2.93; 95% CI, 1.34−4.53; p < 0.05) but the incidence was stable in hepatobiliary neuroendocrine tumors. On multivariate analyzes, age at diagnosis, race, tumor size, grade, tumor type, tumor stage, and surgery were significantly associated with overall survival for hepatobiliary neuroendocrine neoplasms patients. Furthermore, a nomogram based on significant associated factors (age at diagnosis, race, tumor size, stage, type, grade, chemotherapy and surgery) was constructed to predict the 6‐month, 1‐year and 2‐year survival probability, with the concordance indexes of 0.829 (95% CI, 0.800−0.857) for the training cohort and 0.801 (95% CI, 0.745−0.857) for the validation cohort.ConclusionIn this study, the incidence of hepatobiliary neuroendocrine neoplasms has exhibited a persistent upward trend over nearly two decades. Furthermore, this study proposes that a nomogram comprising eight prognostic parameters can effectively quantify the mortality risk in hepatobiliary neuroendocrine neoplasms patients.

ABSTRACTBackgroundMyeloproliferative neoplasms (MPN) present significant management challenges as their constitutional symptoms greatly affect patients' quality of life. While current literature addresses hematological aspects, the full symptom burden and post‐clinic challenges for adult patients, especially in outpatient settings, remain unclear.AimsTo systematically identify and characterize the health distress and challenges experienced by patients with MPN in mainland China.Methods and ResultsThis qualitative study employed semi‐structured interviews with adults diagnosed with MPN (n = 26) to explore their experiences in the outpatient clinic. Colaizzi's descriptive framework guided transcript analysis. Four themes and 12 subthemes were identified: (1) living with the illness, (2) the Sword of Damocles, (3) role conflict, and (4) systemic barriers. These themes informed the development of a trajectory describing the physical and psychological experiences of MPN patients after outpatient visits.ConclusionChinese MPN patients encounter significant health challenges, including persistent symptoms, psychological distress, social limitations, and inadequate self‐management. A comprehensive understanding of their longitudinal experiences is essential for designing effective interventions. Additional research should focus on integrating biopsychosocial management into routine follow‐up care.

ABSTRACTBackgroundOsteosarcoma is the most frequent primary bone malignancy, affecting mainly children, adolescents, and young adults. For the past 40 years, improvements in the survival of patients with osteosarcoma have been minimal, primarily as a consequence of the lack of systemic therapy options beyond traditional cytotoxic agents. In particular, management of metastatic and recurrent disease continues to be a significant clinical challenge.Recent FindingsMouse models of osteosarcoma serve as a valuable tool to study disease biology, metastasis, and response to novel treatments. In recent years, mouse models have been employed to evaluate the efficacy of several innovative drugs, including nanoparticle formulations that can target drug delivery to osteosarcoma tumor cells and diminish off‐target effects. In addition, significant preclinical advancements in immune checkpoint inhibitors and immunotherapies for osteosarcoma have been made with the aid of mouse models.ConclusionThis review provides insight into the advantages and shortcomings of the numerous osteosarcoma mouse models described in the literature, including transgenic, orthotopic, and heterotopic models as well as patient‐derived xenografts. We highlight how these models are currently being used to support preclinical studies focused on the development of novel therapies.