Breast cancer metastasis remains the leading cause of disease-related mortality despite major advances in systemic therapy. Increasing evidence indicates that the circadian-melatonin axis may influence metastatic progression by coordinating endocrine signaling, metabolism, immune responses, and tumor cell plasticity. In this review, we summarize current epidemiological, mechanistic, and translational evidence linking circadian disruption and melatonin to breast cancer metastasis. We discuss how core circadian clock genes and melatonin signaling may influence epithelial-mesenchymal transition, cancer stemness, circulating tumor cell dissemination, tumor metabolism, and immune remodeling. We further highlight the emerging potential roles of melatonin in shaping adipocyte-tumor crosstalk and organ-specific metastatic niches, including bone, lung, liver, and brain, where tissue-specific interactions may influence metastatic colonization. Finally, we discuss the clinical potential of circadian chronotherapy, adjuvant melatonin, and circadian biomarker-guided precision medicine. Although substantial experimental evidence supports the anti-metastatic properties of the circadian-melatonin axis, clinical translation remains limited by context-dependent biological effects and the lack of chronobiology-informed trials. Future studies integrating circadian biomarkers with optimized treatment timing and modern systemic therapies may facilitate precision strategies for preventing and treating metastatic breast cancer.

Fusobacterium nucleatum (F. nucleatum) is increasingly recognized as a key pathobiont in colorectal cancer (CRC), driving tumor progression through immune evasion, inflammation, and metabolic reprogramming. Nevertheless, a comprehensive bibliometric analysis of the literature on F. nucleatum and CRC remains a gap in the current research landscape. Here, we integrate bibliometric trend analysis with a narrative synthesis of key mechanistic insights. Unlike traditional narrative reviews, this study systematically quantifies global research trends, collaboration networks, and thematic evolution using integrated bibliometric tools (CiteSpace, VOSviewer, and Bibliometrix).

This study employed bibliometric analysis to explore the current status of research related to F. nucleatum and CRC. Publications from 2000 to 2025 were retrieved from the Web of Science Core Collection (WOSCC) and Scopus. We used VOSviewer, CiteSpace and Bibliometrix to visualize countries, institutions, authors, keywords, journals and references. Statistical analysis was conducted using Microsoft Office Excel.

The annual number of publications and their relative percentages concerning F. nucleatum and CRC exhibited a steady upward trend from 2009 to 2025, with China (n=708), the United States (n=584), and Italy(n=119) dominating the field. Harvard University and Shanghai Jiao Tong University emerged as leading institutions, while Yu Jun and Shuji Ogino were the most prolific authors. Keyword analysis identified 7 clusters. The most popular journal in this field is Gut. Limitations include potential selection bias from using only two databases (WOSCC and Scopus) and restriction to English-language publications.

Our research provides a comprehensive overview of the research trends and key focal areas in the study of F. nucleatum and CRC. The analysis results show that the annual publication volume in this field has steadily increased, indicating that researchers' attention to this topic has grown continuously. Future research directions suggested by the literature include further exploration of F. nucleatum-targeted therapies, biomarker validation, and multi-omics approaches, although these remain at an early stage.

Testicular intestinal-type adenocarcinoma is an exceedingly rare malignant neoplasm characterized by intestinal epithelial differentiation and accounts for only a minute proportion of testicular malignancies. Its imaging features remain insufficiently characterized and may overlap with those of other testicular tumors, particularly seminoma. When intestinal-type adenocarcinoma is identified in the testis, metastatic adenocarcinoma from the gastrointestinal tract or other extratesticular sites must be excluded before a definitive diagnosis can be established.

We report a rare case of a 33-year-old man in whom a left testicular nodule was incidentally detected during a preconception health examination. The patient had no scrotal pain, swelling, weight loss, altered bowel habits, hematochezia, or other gastrointestinal symptoms. Serum tumor markers were all within normal limits. Imaging evaluation, including ultrasonography and MRI, revealed an irregular hypoechoic nodule measuring approximately 9.7 mm, with peripheral calcifications, prominent peripheral vascularity, and peripheral rim enhancement. Histopathological examination and immunohistochemistry confirmed intestinal-type adenocarcinoma. The patient underwent left partial orchiectomy. Upper gastrointestinal endoscopy, colonoscopy, and contrast-enhanced abdominal and pelvic CT revealed no evidence of an extratesticular primary tumor. No signs of recurrence or metastasis were observed during 6 months of postoperative follow-up.

Testicular intestinal-type adenocarcinoma lacks specific clinical manifestations, and serum tumor markers are usually within normal ranges. On imaging, it may present as a small intratesticular nodule with peripheral enhancement and should be differentiated from seminoma, mixed germ cell tumor, sex cord-stromal tumor, and metastatic adenocarcinoma. Through a literature review, our report provides a comprehensive summary of its multimodal imaging features, including ultrasonography, color Doppler imaging, elastography, and contrast-enhanced MRI, thereby supplementing the limited available data on this rare entity.

Gastric glomus tumor (GGT) is a rare mesenchymal neoplasm with nonspecific clinical and imaging features, often leading to preoperative misdiagnosis. Its longitudinal imaging evolution remains poorly characterized. Herein, we report a 51-year-old man with a GGT in the gastric antrum who underwent 6-year multimodal imaging follow-up, including CT, MRI, and serial endoscopic ultrasonography (EUS). The lesion presented as a well-circumscribed subepithelial nodule with marked and persistent enhancement on CT. It showed slightly low signal intensity on T1-weighted imaging, slightly high signal intensity on T2-weighted imaging, and mild early arterial enhancement followed by persistent marked enhancement on dynamic contrast-enhanced MRI. Over the 6-year follow-up, the lesion showed an overall increase in size and a transition from a homogeneous to a heterogeneous hypoechoic appearance on serial EUS. It was initially misdiagnosed as a gastrointestinal stromal tumor. Histopathology confirmed the diagnosis of GGT. This case highlights that GGT may exhibit characteristic yet dynamic imaging features on long-term follow-up. Recognition of these features across modalities may improve preoperative diagnostic accuracy.

Intraductal papillary mucinous neoplasms (IPMN) are precursors of pancreatic ductal adenocarcinoma (PDAC) and may progress to distinct invasive phenotypes depending on epithelial subtypes. Tubular carcinoma, often arising from pancreatobiliary epithelium, is clinically aggressive and resembles PDAC, whereas colloid carcinoma, typically derived from intestinal epithelium, has a more indolent course. Intraductal oncocytic papillary neoplasms (IOPN), historically considered a subtype of IPMN, are now recognized as a distinct entity characterized by abundant eosinophilic cytoplasm, complex papillary architecture, and unique molecular alterations. Although the heterogeneity of intraductal pancreatic neoplasms (i.e., IPMN, IOPN, ITPN) is recognized, the mechanisms and temporal dynamics underlying their malignant progression remain poorly understood. We report the case of a female patient in her 80s with a pancreatic body cyst first identified in her 40s. After decades of radiologic stability, she underwent a middle pancreatectomy in 2017, which showed a 1.5 cm oncocytic carcinoma (pT1N0) arising from an IOPN. After surgical resection, she remained disease-free for eight years. In 2025, she developed a new pancreatic head cyst and underwent pancreaticoduodenectomy, which revealed a colloid carcinoma (pT3N0) arising from an intestinal-type IPMN. Molecular profiling of the 2025 specimen demonstrated shared driver alterations in the intestinal-type IPMN and associated colloid carcinoma (KRAS p.G12V and GNAS p.R201C), with BRAF p.D594Y detected in the IPMN component and MTAP deletion detected in the invasive component. Sequencing of the 2017 specimen was not feasible due to limitations of archival tissue. This case describes the metachronous clinical presentation and histologic diagnosis of oncocytic and colloid carcinomas eight years apart within a clinical history spanning nearly four decades. Because sequencing of the 2017 tumor was unsuccessful, clonal independence cannot be established. The case supports prolonged surveillance and further molecular study.

Hepatoblastoma is the most prevalent pediatric malignant liver neoplasm, and despite substantial advances in multimodal treatment, outcome data from Southeast European pediatric centers remain limited. The aim of this study was to evaluate the clinical characteristics, treatment approaches, surgical management, and outcomes of children treated for hepatoblastoma at a tertiary pediatric institution over a 17-year period.

This retrospective single-center cohort study included 24 pediatric patients treated between January 2008 and March 2025. Clinical variables included age, sex, tumor size, PRETEXT stage, metastatic disease, and vascular involvement. Treatment variables comprised chemotherapy protocol, surgical procedure, liver transplantation, and resection margin status, while outcome measures included relapse, overall survival, and normalization of serum α-fetoprotein levels.

With the exception of one child who died before treatment could be initiated, all patients underwent surgical treatment following liver biopsy and preoperative chemotherapy. Overall, six children (25.0%) died, whereas 18 were alive at the time of analysis, corresponding to an overall survival rate of 75.0% with a median follow-up of 9.0 years. All patients with PRETEXT 1 and PRETEXT 2 disease survived, whereas survival among patients with PRETEXT 3-4 disease was significantly lower (100.0% vs. 50.0%, p = 0.014). Postoperative relapse occurred in two of the 23 treated patients (8.7%), and serum α-fetoprotein levels normalized after treatment in all surviving patients.

In this retrospective single-center cohort, multimodal treatment of hepatoblastoma achieved an overall survival of 75.0%, with particularly favorable outcomes in patients with PRETEXT 1-2 disease and negative surgical margins. These findings provide valuable long-term real-world evidence on hepatoblastoma management at a tertiary pediatric referral center.

To characterize recurrence heterogeneity among patients with VI-RADS 2 non-muscle-invasive bladder cancer (NMIBC) and to develop and internally validate a recurrence-free survival (RFS) prediction model incorporating quantitative MRI features.

This retrospective study included 342 patients with pathologically confirmed VI-RADS 2 NMIBC, who were randomly divided into training and internal validation cohorts. Clinical and quantitative MRI variables were evaluated using Cox regression, least absolute shrinkage and selection operator regression, Boruta, and recursive feature elimination. Six survival prediction algorithms were developed and compared. The selected model was further compared with a clinical Cox model and the European Association of Urology (EAU) risk stratification system using the concordance index (C-index), time-dependent area under the curve (AUC), calibration, Brier score, and decision curve analysis.

Among 342 patients, 111 (32.5%) experienced recurrence. Six predictors were retained: tumor number, maximum tumor vertical distance, maximum tumor diameter, maximum tumor-base contact length, mean apparent diffusion coefficient (ADC) at the tumor base, and minimum ADC within the tumor. The random survival forest (RSF) model achieved C-index values of 0.832 and 0.757 in the training and validation cohorts, respectively. In the validation cohort, the corresponding C-index values were 0.417 for the clinical Cox model and 0.534 for the EAU risk stratification system. The RSF model also yielded higher time-dependent AUCs than both reference models and greater net benefit at the 60-month horizon. RSF-derived risk groups showed significantly different RFS in both cohorts; in the validation cohort, the hazard ratio for the high-risk versus low-risk group was 5.30 (95% confidence interval, 2.39-11.76).

Within this single-center cohort, recurrence risk varied substantially among patients with VI-RADS 2 NMIBC. An RSF model incorporating quantitative MRI features and tumor number showed better internal discrimination than the clinical Cox model and the EAU risk stratification system and separated patients into distinct risk groups. These findings suggest that quantitative MRI features may complement conventional clinical assessment in this imaging-defined subgroup. Prospective multicenter external validation with longer follow-up is required before the model can be considered for clinical use.

Adults with acute leukemia admitted to intensive care have high early mortality. Whether acute lymphoblastic leukemia (ALL) adds prognostic information beyond baseline severity remains clinically important.

We performed a retrospective MIMIC-IV cohort study of 486 first ICU stays from 372 adults with acute leukemia. Primary outcomes were hospital and ICU mortality. ALL was compared with a predominantly acute myeloid leukemia comparator using complementary confounder-only and severity-adjusted models and ICD-derived remission stratification, with directional replication in an independent eICU cohort.

ALL admissions were younger and less severely ill at ICU entry. Crude hospital mortality was lower in ALL than in the predominantly AML comparator (23.8% vs. 38.6%; P = 0.010). After adjustment for age and comorbidity alone, ALL showed a non-significant reduction in the odds of hospital mortality (adjusted OR, 0.688; 95% CI, 0.385-1.228). Adding first-day Sequential Organ Failure Assessment (SOFA), which partly overlaps with leukemia-related complications, moved this estimate toward the null (adjusted OR, 0.905; 95% CI, 0.485-1.689). ICU-mortality estimates were also non-significant, although the severity-adjusted ICU estimate crossed the null (confounder-only adjusted OR, 0.690; severity-adjusted OR, 1.076). Because first-day SOFA may lie on the subtype-to-outcome pathway, the confounder-only estimate is reported as the total-association estimate (not conditional on the possible mediator), and all confidence intervals remained wide. Model calibration and discrimination were acceptable. In an independent eICU cohort (n=82), the crude and severity-adjusted ALL estimates for hospital mortality (odds ratios 0.667 and 0.445) were likewise non-significant.

In MIMIC-IV, the crude ALL survival advantage narrowed after adjustment and was not statistically significant. In eICU, crude and severity-adjusted estimates were likewise non-significant but moved further from, rather than toward, the null. Wide confidence intervals in both cohorts, the small ALL sample, overlap between first-day SOFA and leukemia-related complications, and unmeasured leukemia-specific factors leave a modest residual subtype effect possible. These are within-ICU associations affected by selection into intensive care; incomplete post-discharge death ascertainment mainly limits longer-horizon interpretation.

To analyze the clinicopathological features, surgical management, and long-term prognosis of a composite pheochromocytoma (CP; pheochromocytoma combined with ganglioneuroma) arising 13 years after resection of a primary adrenal pheochromocytoma, with the aim of improving the clinical diagnosis and management of this rare neoplasm.

A 61-year-old Han male had undergone left adrenal pheochromocytoma resection 13 years prior to the current presentation. An asymptomatic left adrenal nodule was incidentally detected during a routine physical examination, and the patient was subsequently admitted to the Department of Urology at The Third Hospital of Mianyang. He denied any history of other chronic systemic illnesses. Admission biochemistry revealed only a mild elevation of epinephrine, with the concentration remaining below twice the upper limit of normal. Abdominopelvic contrast-enhanced computed tomography (CT) identified a well-circumscribed hypodense nodule measuring 2.6 × 2.1 cm beneath the left adrenal gland, demonstrating marked nodular and peripheral ring enhancement; a separate hypodense nodule with a maximum diameter of 1.8 cm was also noted in the right adrenal fossa. Based on his disease history and imaging findings, recurrence of left adrenal pheochromocytoma was strongly suspected, and a synchronous right adrenal pheochromocytoma could not be excluded. The patient consented only to partial left adrenalectomy. Intraoperative exploration revealed adhesions among the descending colon, peritoneum, and spleen, as well as multiple solid masses (maximum size 2.0 × 2.0 cm) in the left adrenal region that were densely adherent to the pancreatic parenchyma. The resected specimens were submitted for pathological evaluation. Histopathological examination confirmed a composite pheochromocytoma with cystic change, multifocal coagulative necrosis, and adipose tissue invasion. The patient experienced an uneventful postoperative recovery. During the subsequent 11-month follow-up period, no recurrence or distant metastasis was detected, and the patient remained clinically stable.

It remains challenging to definitively establish whether the left adrenal composite pheochromocytoma (CP) detected in this patient represents true tumor recurrence 13 years after the initial surgery. Archival pathological slides from the primary operation were unavailable for comparative histologic and clonal analysis. Moreover, the original lesion was diagnosed as a pure pheochromocytoma, whereas the current mass harbors an additional mature ganglioneuromatous component displaying distinct histological features. Given the lack of evaluable surgical margins from the initial partial adrenalectomy, the possibility of minimal residual disease cannot be excluded. Accordingly, two possibilities are proposed: late ipsilateral recurrence of the original chromaffin tumor, or a metachronous de novo primary CP arising independently in the left adrenal gland. In contrast to most previously documented CP cases, this patient exhibited isolated mild epinephrine elevation without catecholamine-related clinical manifestations, underscoring that regular physical screening and postoperative histopathology constitute the main diagnostic pillars. Surgical resection remains the first-line therapy. Regardless of its origin, long-term regular surveillance is mandatory, given the inherent metastatic potential of pheochromocytomas and paragangliomas (PPGLs).

Cancer immunotherapy has achieved remarkable clinical success; however, therapeutic resistance remains a major challenge. Increasing evidence suggests that gut microbiota-derived metabolites play a critical role in modulating host immune responses and influencing treatment outcomes. This study aimed to systematically characterize the global research landscape and identify emerging trends in this field using bibliometric approaches.

Publications were retrieved from the Web of Science Core Collection (WoSCC) and Scopus databases based on predefined search strategies. Only English-language articles and reviews were included. Bibliographic records were integrated and deduplicated using the bibliometrix R package. Descriptive analyses were performed to evaluate publication outputs, countries, institutions, authors, and journals. CiteSpace was used for reference burst detection, and VOSviewer was applied to construct keyword co-occurrence networks.

A total of 2,979 publications from 1973 to March 2026 were included, comprising 1,593 reviews and 1,386 original articles. China contributed the largest number of publications (1,121; 37.63%), followed by the United States (499; 16.75%). Notably, the United States exhibited the highest H-index and centrality, indicating its leading role in global research impact and collaboration networks. Sichuan University was the most productive institution (115 publications), with six of the top ten institutions located in China. Laurence Zitvogel (28 publications) and Guido Kroemer (22 publications) were the leading authors in this field. Frontiers in Immunology published the highest number of relevant articles (277). Keyword and temporal analyses indicated a shift from descriptive microbiome profiling toward mechanism-oriented and translational research. Recent hotspots include "immunomodulation", "the gut-liver axis", "intratumoral microbiota", and "microbial metabolites".

Microbial metabolites have emerged as key functional mediators shaping responses to cancer immunotherapy, reflecting a shift from microbiome composition toward metabolite-centered mechanisms. This field is undergoing a transition from descriptive profiling to mechanism-oriented and translational research. These findings provide important insights for developing microbiota-targeted strategies to enhance the efficacy of cancer immunotherapy.