This study aimed to compare endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in managing obstructive hydrocephalus secondary to posterior fossa tumors in pediatric patients.

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Searches of PubMed, Cochrane, and Embase databases were performed on April 1, 2025. Primary outcomes included mortality and control of intracranial hypertension, while secondary outcomes encompassed infection and bleeding rates.

The search identified 417 studies, of which 12 met the inclusion criteria, encompassing 917 pediatric patients (360 ETV and 557 VPS). Ages ranged from 0 to 19 years, with 61% being male. No significant differences were observed between ETV and VPS in terms of mortality (OR 0.49; 95% CI 0.14-1.73; p = 0.27; I² = 0%), control of intracranial hypertension (OR 0.79; 95% CI 0.49-1.25; p = 0.31; I² = 66%), or need for reoperation (OR 0.65; 95% CI 0.43-1.00; p = 0.05; I² = 58%). However, ETV was associated with a significantly lower infection rate (OR 0.15; 95% CI 0.03-0.73; p = 0.02; I² = 0%) and a lower incidence of bleeding complications (OR 0.40; 95% CI 0.17-0.97; p = 0.04; I² = 0%).

ETV and VPS demonstrated comparable outcomes regarding mortality, ICP control, and need for reoperation. ETV was associated with lower rates of infection and overall intracranial hemorrhage, although no difference was observed for intracerebral hemorrhage alone. Larger prospective studies are needed to confirm these findings.

Endoscopic submucosal dissection is the standard treatment for superficial esophageal squamous cell carcinoma. However, esophageal preservation following this procedure increases the risk of metachronous multiple cancers. Lugol-voiding lesion grade and alcohol-related genetic polymorphisms have been identified as risk factors, but the role of nonspecific mediastinal lymphadenopathy remains unclear.

We retrospectively analyzed the data of 154 patients who underwent curative endoscopic submucosal dissection for esophageal squamous cell carcinoma at Hamamatsu University Hospital between 2015 and 2024. Pretreatment computed tomography was used to evaluate the Lugol-voiding lesion grade and nonspecific mediastinal lymphadenopathy. Associations with pathological findings and the development of metachronous multiple esophageal squamous cell carcinoma were assessed using Kaplan-Meier and Cox regression analyses.

Nonspecific mediastinal lymphadenopathy was identified in 68 patients (59.6%). Pathological analysis including 154 patients revealed that nonspecific mediastinal lymphadenopathy was significantly associated with lymphovascular invasion (P = 0.026) but not with invasion depth or curative resection. During follow-up and metachronous analysis including 114 patients, 21 patients developed metachronous multiple esophageal squamous cell carcinoma. Both Lugol-voiding lesion grade and nonspecific mediastinal lymphadenopathy were independent predictors of recurrence. Subgroup analysis restricted to Lugol-voiding lesion grade B/C cases confirmed that nonspecific mediastinal lymphadenopathy remained predictive of recurrence-free survival (P = 0.007).

Nonspecific mediastinal lymphadenopathy independently predicts the development of metachronous esophageal squamous cell carcinoma after endoscopic submucosal dissection. Evaluation of nonspecific mediastinal lymphadenopathy in combination with Lugol-voiding lesion grade may improve risk stratification and optimize surveillance strategies.

Low-pass whole-genome sequencing (LP-WGS) of circulating tumor DNA (ctDNA) is increasingly recognized for its utility in identifying somatic copy-number aberration (CNA). In this study, we analyzed LP-WGS ctDNA data from 73 pediatric patients with neuroblastic tumor and 11 healthy controls to explore diagnostic value of ctDNA CNA burden (including the genotypings) with a customized bioinformatics workflow. We found that a high baseline ctDNA CNA burden [tumor DNA fraction (TFx) ≥0.2%] was present in 36 of 41 patients (87.80%) with neuroblastoma, six of 22 patients (27.27%) with ganglioneuroblastoma, and three of 10 patients (30%) with ganglioneuroma. High baseline ctDNA CNA burden could predict high-risk neuroblastic tumors with an area under curve (AUC) of 0.95, sensitivity of 94.12%, and specificity of 100%. Frequent chromosomal copy-number changes, including chr17q gain, chr7 gain, chr3p loss, and chr11q loss, were found in ctDNA. Gain of chr17q demonstrated the highest diagnostic value with an AUC of 0.92, indicating strong sensitivity and specificity for detecting high-risk neuroblastic tumors. The homologous recombination deficiency score in the high- and intermediate-risk groups was significantly elevated compared with those in the low-/very low-risk group. The TFx levels and segmental alterations significantly decreased in patients with neuroblastic tumor who underwent chemotherapy, from median TFx = 13.82% before treatment to 0.24% after treatment (P < 0.0001). Our findings highlight the effectiveness of LP-WGS ctDNA CNA analysis as a promising approach for diagnosis and risk stratification of pediatric neuroblastic tumors and for monitoring chemotherapy response. Particularly, ctDNA analysis is minimally invasive, rapid, and cost-effective, which could bring additional benefits in pediatric practices.

Our results support the development of ctDNA CNA analysis as a robust and minimally invasive approach for early detection, molecular diagnosis, and risk stratification of peripheral neuroblastic tumors.

DNA damage response genes (DDRG), implicated in several cancers as both predisposing risk factors as well as biomarkers for aggressiveness, have not been fully explored in multiple myeloma (MM).

Herein, we analyzed disease associations of pathogenic variations in nine putative candidate genes using 3 446 MM cases and 323 233 cancer-free controls.

Increased MM risk was found to be associated with inherited rare pathogenic mutations in TP53, ATM, CHEK2, KDM1A, and ARID1A, with an enrichment of these variants among individuals with early onset or family history of MM. Individuals with TP53 or ATM germline mutations are also likely to have worse overall survival.

Our results suggest expansion of the phenotypic spectrum of some of these DDRG to include MM. The identification of these germline predisposition genes opens the avenue for targeted screening of higher risk individuals especially those with young-onset or a family history of plasma cell gammopathies.

Erdheim-Chester disease (ECD) is a rare disease characterized by the accumulation of neoplastic histiocytes in various extra-nodal tissues. Tissue biopsies involved by ECD are difficult to distinguish from reactive inflammatory infiltrates given the bland appearance of the neoplastic histiocytes. Confirmation of the ECD diagnosis often relies on molecular studies to confirm BRAF V600E mutation or other activating mutations involving MAPK pathway genes. In this study, we examined the diagnostic utility of cyclin D1 and pERK as immunohistochemical markers of MAPK pathway activation in ECD compared with its histopathologic mimics. The cohort included 41 clinically confirmed ECD patients, most with known genetic alterations in MAPK pathway genes (n=38). In 3 cases no mutation was identified. 37 of 41 (90%) of ECD cases showed cyclin D1 overexpression, with frequent staining in the cytoplasm as well as the nucleus. pERK expression was observed in 32 of 39 (82%) cases. Cyclin D1 staining was negative in histopathologic mimics of ECD, apart from weak patchy staining in fat necrosis and uniform staining in a subset of cases of juvenile/adult xanthogranuloma. While not entirely sensitive or specific, in the proper clinical and radiologic context strong nuclear and cytoplasmic cyclin D1 expression within histiocytic infiltrates helps to support a diagnosis of ECD.

Genetic disorders in neonates often present with overlapping clinical features, posing significant diagnostic challenges. Glycogen storage diseases (GSD) disrupt glycogen metabolism, leading to energy deficits. Pathogenic variants in the Wilms tumor 1 (WT1) gene represent a rare but significant cause of early-onset steroid-resistant nephrotic syndrome (SRNS), associated with a broad range of both kidney and extrakidney phenotypic manifestations. The coexistence of these genetic diseases in a single patient has not been previously reported. Herein, we present a case of a newborn with symptomatic hypoglycemia and metabolic acidosis that was transferred to the Neonatal Intensive Care Unit. During hospitalization, he developed hyponatremia and nephrotic-range proteinuria, a genetic test was performed, and he was transferred to the nephrology unit. Genetic analysis identified a compound homozygous mutation (c.247 C > T) in the G6PC gene, confirming glycogen storage disease type 1a (GSD-1a) and a pathogenic WT1 mutation (c.1400G > A) associated with Denys-Drash syndrome. This case highlights the importance of a multidisciplinary approach in the evaluation and management of neonates with a complex combination of genetically-determined conditions.

Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related deaths worldwide. Adipocyte Plasma Membrane Associated Protein (APMAP) is a glycosylated type II transmembrane protein, and APMAP induces malignant metastasis of colorectal cancer. However, the role and mechanism of APMAP in NSCLC remain unknown. We aimed to study the APMAP regulation on NSCLC. APMAP mRNA levels in NSCLC tissues were tested by quantitative reverse transcription-PCR (qRT-PCR). APMAP protein levels in NSCLC tissues and cells were determined via Western blot. Also, the association between APMAP expressions and NSCLC clinicopathology was assessed using Chi-square test. After silencing APMAP (sh-APMAP) in NSCLC cells, APMAP's roles in NSCLC were revealed by Western blot, Cell Counting Kit-8 (CCK-8) assay, Transwell, Fe²⁺ level analysis, and immunofluorescence assays. Meanwhile, APMAP mechanism in NSCLC was verified through Human TFDB and PROMO databases, qRT-PCR, Western blot, dual-luciferase reporter assay, CCK-8 experiment, Transwell, analysis of Fe²⁺, reactive oxygen species levels, and Clinical Bioinformatics Home. Also, APMAP function in vivo was examined using a tumor xenograft model, immunohistochemistry assay, and Western blot. APMAP expressions were up-regulated in NSCLC tissues and cells. Moreover, patients with high APMAP expression exhibited a poorer overall survival rate. APMAP expression was closely related to TNM stage, distant metastasis, and tumor differentiation. Functionally, APMAP knockdown repressed NSCLC cell proliferation and invasion, and induced cell ferroptosis. Mechanistically, transcription factor YY1 induced APMAP expression. Meanwhile, APMAP expressions were decreased after interfering with YY1, while APMAP expressions were increased after overexpressing YY1. Also, co-transfection experiments demonstrated that YY1 overexpression enhanced the fluorescence intensity of APMAP-WT promoter. Importantly, YY1 overexpression promoted NSCLC cell proliferation and invasion, and repressed cell ferroptosis, yet these effects were reversed after APMAP knockdown. Moreover, knocking down APMAP reduced NSCLC proliferation in vivo, mainly through reduced tumor volume, reduced KI-67 and GPX4 expressions, and decreased p-pI3K, p-AKT, and p-mTOR protein levels. APMAP regulated by YY1 transcription enhanced NSCLC proliferation, invasion, and repressed cell ferroptosis via activating PI3K/AKT/mTOR.

Precancers, defined as normal-appearing or morphologically altered tissues with a risk of oncogenesis, exhibit various detectable manifestations across anatomical sites, including epithelial dysplasia, metaplasia, hyperplasia, and stromal fibrosis. Considering the prevailing assumption that most cancers arise from precancers, early intervention at the precancerous stage has immense potential to reduce cancer-related morbidity and mortality. However, the complex signaling networks governing precancer initiation and progression remain elusive, hampering the development of effective targeted interventions. This review synthesizes three critical dimensions of precancer biology: historical foundations tracing the conceptual evolution of precancer research over the past century; mechanisms underlying the multistep progression of precancer biology, encompassing epithelial and macro/microenvironmental remodeling; and signaling networks cataloging dysregulated pathways and their therapeutic potential. Over 10 signaling pathways, including the transforming growth factor-β (TGF-β), p53, Wnt, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) pathways, drive multistep malignant transformation. We further synthesize emerging evidence supporting microenvironmental dominance, proposing the novel "soil degeneration" hypothesis. This paradigm shift underscores the necessity for dual-window intervention in which early-phase microenvironmental normalization prevents the establishment of precancerous lesions and advanced-phase treatment concurrently addresses epithelial malignancy and stromal degeneration. This review bridges foundational molecular discoveries with translational clinical potential and advocates for precision intervention frameworks that extend from biomarker-guided risk assessment to synergistic remodeling of the precancer microenvironment, thereby redefining precancer intervention in the molecularly targeted era.

Age and sex are known to influence outcomes in neuroendocrine neoplasms (NENs), yet their molecular determinants remain poorly defined. We queried a real-world dataset of gastrointestinal (GI) tract and pancreatic (P) NENs and characterized their clinical, molecular, and immune profiles.

1935 cases (GI: n = 1431, P: n = 504) of NENs were analyzed using Next Generation or Whole Exome Sequencing of DNA, and 1211/1935 cases (GI: n = 917, P: n = 294) underwent Whole Transcriptome Sequencing. We compared the molecular and immune profile with respect to age and sex.

Older age at diagnosis was associated with worse survival in both GI- and P-NENs. In patients with GI-NENs, there was decreased survival in males compared to females. In GI-NENs, TP53, RB1, FAT1, and KMT2D mutations, as well as immune checkpoint gene (ICG) expressions of LAG3, CD80, and HAVCR2 and M1 macrophages increased with increasing age while APC mutations and M2 macrophages decreased with increasing age. In P-NENs, TP53, RB1, KRAS, and SMAD4 mutations and CD4+ T cells increased with increasing age while MUTYH and NTHL1 mutations and M2 macrophages decreased with increasing age. In GI-NENs, TP53, FBXW7, and TERT (promoter) mutations and genomic loss of heterozygosity (gLOH) were increased in males. In P-NENs, PIK3CA mutations and dMMR/MSI-H were increased in females.

Our study queries one of the largest datasets of GI- and P-NENs to date and highlights distinct age- and sex-specific molecular and immune profiles. Given the exploratory nature of these analyses and borderline significance, these results remain hypothesis-generating, providing an initial framework for future validation studies.

Postoperative nutrition after pancreatoduodenectomy (PD) remains controversial. Although many centers routinely place a feeding jejunostomy tube (FJT) after PD, it is associated with morbidity. We conducted this study to compare the perioperative outcomes with and without FJT placement post-PD.

This was an open-label randomized controlled trial, in which the FJT was placed in one arm and the nasojejunal tube (NJT) in the other. All patients with periampullary neoplasm who underwent pylorus resecting PD were included in this study. The primary outcome assessed was clinically relevant delayed gastric emptying (CR-DGE), and the secondary outcomes were clinically relevant postoperative pancreatic fistula (CR-POPF), postoperative complications, and hospital stay.

Forty patients were allocated to the FJT and NJT groups, and the two groups were comparable in baseline demographics, disease characteristics, and perioperative outcomes, including CR-POPF rates. The FJT group had a significantly higher CR-DGE rate (55% vs. 25%, p = 0.006), required increased use of prokinetic drugs (77.5% vs. 45%, p = 0.003), and had a longer median postoperative hospital stay (11 vs. 9 days, p = 0.007). Both groups had similar tube-related complications. In the NJT group, 22.5% of the patients with CR-DGE required parenteral nutrition. On multivariate analysis, the presence of FJT [adjusted odds ratio (aOR), 6.030 (1.431-25.402), p = 0.014] and intra-abdominal collection [aOR, 7.108 (1.026-49.224), p = 0.047] were independent risk factors for CR-DGE.

Post-PD placement of FJT was an independent risk factor for CR-DGE. Hence, the routine use of the FJT can be omitted after PD without compromising postoperative morbidity and nutrition.

The trial was registered with the Clinical Trial Register with CTRI number: CTRI/2021/02/030942 (https://ctri.nic.in/Clinicaltrials/advancesearchmain.php).