Gut microbiota composition and metabolic characteristics in patients with Craniopharyngioma.

BACKGROUND: Emerging evidence suggests that the gut microbiota is associated with various intracranial neoplastic diseases. It has been observed that alterations in the gut microbiota are present in gliomas, meningiomas, and pituitary neuroendocrine tumors (Pit-NETs). However, the correlation between gut microbiota and craniopharyngioma (CP), a rare embryonic malformation tumor in the sellar region, has not been previously mentioned. Consequently, this study aimed to investigate the gut microbiota composition and metabolic patterns in CP patients, with the goal of identifying potential therapeutic approaches. METHODS: We enrolled 15 medication-free and non-operated patients with CP and 15 healthy controls (HCs), conducting sequential metagenomic and metabolomic analyses on fecal samples to investigate changes in the gut microbiota of CP patients. RESULTS: The composition of gut microbiota in patients with CP compared to HCs show significant discrepancies at both the genus and species levels. The CP group exhibits greater species diversity. And the metabolic patterns between the two groups vary markedly. CONCLUSIONS: The gut microbiota composition and metabolic patterns in patients with CP differ significantly from the healthy population, presenting potential new therapeutic opportunities.

Risk factors for cerebrospinal fluid leak after extended endoscopic endonasal surgery for adult patients with craniopharyngiomas: a multivariate analysis of 364 cases.

OBJECTIVE: Over the last decade, the extended endoscopic endonasal approach (EEEA) has evolved as a credible surgical alternative for removing craniopharyngiomas. However, postoperative cerebrospinal fluid (CSF) leak remains one of the most pressing concerns. Craniopharyngiomas often invade the third ventricle, resulting in a higher rate of third ventricle opening after surgery and potentially increasing the risk of postoperative CSF leak. Identifying the risk factors associated with CSF leak after EEEA for craniopharyngiomas may have more clinical value. Nevertheless, there is a lack of systematic studies on the topic. Previous studies yielded inconsistent results, probably due to heterogeneous pathologies or small sample sizes. Hence, the authors present the largest known single-institution case series of the use of purely EEEA for craniopharyngiomas to systematically study the risk factors for postoperative CSF leak. METHODS: The authors retrospectively reviewed 364 cases of adult patients with craniopharyngiomas who were treated at their institution from January 2019 to August 2022, and they analyzed the risk factors for postoperative CSF leak. RESULTS: The overall rate of postoperative CSF leak was 4.7%. In the univariate analysis, larger dural defect size (OR 8.293, 95% CI 3.711-18.534, p < 0.001) and lower preoperative serum albumin level (OR 0.812, 95% CI 0.710-0.928, p = 0.002) were associated with higher rates of postoperative CSF leak. Predominantly cystic tumors (OR 0.325, 95% CI 0.122-0.869, p = 0.025) were linked to decreased risk of postoperative CSF leak. However, postoperative lumbar drainage (OR 2.587, 95% CI 0.580-11.537, p = 0.213) and third ventricle opening (OR 1.718, 95% CI 0.548-5.384, p = 0.353) were not related to postoperative CSF leak. In the multivariate analysis, larger dural defect size (OR 8.545, 95% CI 3.684-19.821, p < 0.001) and lower preoperative serum albumin level (OR 0.787, 95% CI 0.673-0.919, p = 0.002) were identified as independent risk factors for postoperative CSF leak. CONCLUSIONS: The authors' repair technique yielded a reliable reconstructive outcome for high-flow CSF leak in EEEA for craniopharyngioma. Lower preoperative serum albumin level and larger dural defect size were identified as independent risk factors for postoperative CSF leak, potentially providing new insights into minimizing the risk of postoperative CSF leak. Third ventricle opening was not associated with postoperative CSF leak. Lumbar drainage may not be necessary for high-flow intraoperative leak, but this finding may require validation with a prospective randomized controlled trial in the future.

Comparative genomics analysis provide insights into evolution and stress responses of Lhcb genes in Rosaceae fruit crops.

BACKGROUND: Light-harvesting chlorophyll a/b b evelopment of higher plants and in response to abiotic stress. Previous works has demonstrated that that Lhcb genes were involved in the phytochrome regulation and responded to the different light and temperature conditions in Poaceae (such as maize). However, the evolution and functions of Lhcb genes remains poorly characterized in important Rosaceae species. RESULTS: In this investigation, we conducted a genome-wide analysis and identified a total of 212 Lhcb genes across nine Rosaceae species. Specifically, we found 23 Lhcb genes in Fragaria vesca, 20 in Prunus armeniaca, 33 in Malus domestica 'Gala', 21 in Prunus persica, 33 in Rosa chinensis, 29 in Pyrus bretschneideri, 18 in Rubus occidentalis, 20 in Prunus mume, and 15 in Prunus salicina. Phylogenetic analysis revealed that the Lhcb gene family could be classified into seven major subfamilies, with members of each subfamily sharing similar conserved motifs. And, the functions of each subfamily was predicted based on the previous reports from other species. The Lhcb proteins were highly conserved within their respective subfamilies, suggesting similar functions. Interestingly, we observed similar peaks in Ks values (0.1-0.2) for Lhcb genes in apple and pear, indicating a recent whole genome duplication event (about 30 to 45 million years ago). Additionally, a few Lhcb genes underwent tandem duplication and were located across all chromosomes of nine species of Rosaceae. Furthermore, the analysis of the cis-acting elements in the 2000 bp promoter region upstream of the pear Lhcb gene revealed four main categories: light response correlation, stress response correlation, hormone response correlation, and plant growth. Quantitative expression analysis demonstrated that Lhcb genes exhibited tissue-specific expression patterns and responded differently to low-temperature stress in Rosaceae species. CONCLUSIONS: These findings shed light on the evolution and phylogeny of Lhcb genes in Rosaceae and highlight the critical role of Lhcb in pear's response to low temperatures. The results obtained provide valuable insights for further investigations into the functions of Lhcb genes in Rosaceae, and these functional genes will be used for further fruit tree breeding and improvement to cope with the current climate changes.

A Full View of Papillary Craniopharyngioma Based on Expanded Endonasal Approach: A Comprehensive Clinical Characterization of 101 Cases.

OBJECTIVE: The enlarged endonasal approach (EEA) has emerged as the preferred surgical procedure for removing craniopharyngiomas, due to its advantages of direct visualization and reduction of blind corners. However, owing to a low incidence of papillary CPs (PCPs) compared to adamantinomatous CPs (ACPs), a full view of PCP based on the EEA approach is limited. In this paper, the authors present the largest series to date analyzing the clinical characteristics based on the EEA approach for PCPs. METHODS: A retrospective review was conducted on 101 PCPs patients who underwent endoscopic endonasal surgery (EEA) and whose condition was confirmed via postoperative pathology. The PCPs were classified into three types based on MRI data and intraoperative findings from EEA: suprasellar/intra-suprasellar (3V floor intact) type (Type I), suprasellar/intra-suprasellar (3V floor invasive) type (Type II), and intra-third ventricle type (Type III). The general characteristics of the three types of tumors were summarized, and postoperative follow-up was conducted to record detailed information on changes in vision, endocrine replacement, tumor recurrence, and quality of life. RESULTS: Out of the 101 cases, 36 (36.64%) were classified as type I, 52 (51.49%) as type II, and 13 (12.87%) as type III. The mean age of type III patients was 40.46 ± 14.15 years old, younger than the other two types (p = 0.021). Headache (84.62%) and memory decline (61.54%) were prominent features in patients with type III (p = 0.029). Visual impairment was more common in type II (80.77%, p = 0.01). Gross total resection (GTR) was achieved in 91 patients (90.10%). There were no significant differences in GTR rates among the three types of tumors. There were significant differences in quality of life among the three types of PCP (p = 0.004), and type III presented with the highest rate of good postoperative quality of life (92.31%) based on the KPS score. Thirteen (12.87%) tumors recurred within a mean follow-up time of 38 (range, 8-63) months. Type II PCPs (OR 5.826, 95%CI 1.185-28.652, p = 0.030) and relapsed patients (OR 4.485, 95%CI 1.229-16.374, p = 0.023) were confirmed as independent risk factors for tumor recurrence. CONCLUSIONS: Most of the PCPs including intra-third ventricle PCPs can be safely and effectively removed through neuroendoscopy with EEA. Suprasellar/intra-suprasellar (third cerebral ventricle floor-invasive) type PCPs may have a worse postoperative quality of life compared to the other two types, and it may be a strong predictor of tumor recurrence.

Correlations between the expression of molecules in the TGF-ß signaling pathway and clinical factors in adamantinomatous craniopharyngiomas.

Objective: To investigate the clinical and pathological factors associated with preoperative hypothalamus invasion and postoperative outcomes of adamantinomatous craniopharyngiomas (ACPs) after the expanded endonasal approach (EEA) resection. Methods: Ninety-three specimens of ACPs, consisting of 71 primary and 22 recurrent tumors, were investigated for the expression of TGF-ß1, SMAD2, SMAD3, and ß-catenin by immunohistochemistry staining. The clinical information of relevant patients, including the extent of resection, hypothalamus invasion, endocrinopathy, complications, and prognosis, was reviewed. The relationships between the expression of these immunopathological markers and clinical factors were analyzed. Results: Endocrinological dysfunctions were more common in recurrent patients and primary patients with hypothalamus invasion in the comparisons. For recurrent patients, the rate of gross total resection (GTR) was significantly lower than for primary patients (63.6% vs. 90.1%, P = 0.007). According to radiological and intraoperative findings, invasive ACPs (IACPs) included 48 (67.6%) cases in primary tumors. The expression of TGF-ß1 and ß-catenin was significantly higher in recurrent tumors (P = 0.021 and P = 0.018, respectively) and IACPs (P = 0.008 and P = 0.004, respectively). The expression level of TGF-ß1 was associated with hypothalamus involvement (Puget grade, P = 0.05; Vile grade, P = 0.002), postoperative endocrinopathy (P = 0.01), and pituitary stalk preservation (P = 0.008) in primary patients. In addition, the extent of resection, treatment history, hypothalamic invasion, and level of TGF-ß1 expression had significant influences on tumor recurrence/progression after surgery separately. Conclusion: Our study demonstrated the potential role of TGF-ß1 in the regulation of hypothalamus invasion in ACPs and the prediction of prognosis after EEA surgery. The TGF-ß signaling pathway may represent a crucial mechanism in the aggressive behavior and progression of ACPs.

Clinical Significance of Plasma Leptin and Its Receptors mRNA Expression in Craniopharyngiomas: A Prospective Study.

Craniopharyngioma (CP) is a benign tumor with a high rate of obesity and frequent recurrence. Moreover, the role of leptin/leptin receptors axis in obesity and the prognosis of CP is still unknown. Plasma leptin concentration and mRNA expression of leptin receptors were assessed in patients with CP. Moreover, the association between leptin/leptin receptors axis, weight-related outcomes, and progression-free survival (PFS) were explored in CP patients. Leptin receptors overexpressed in CP tumor tissue were compared to normal brain tissue (p < 0.05); compared to healthy controls, the concentration of leptin was elevated in CP with or without matched age, sex, and body mass index (BMI) (p < 0.05). The high plasma leptin level was an independent risk predictor for significant weight gain (adjusted odds ratio (aOR) = 2.29, and p = 0.030) and new-onset obesity (aOR = 6.64, and p = 0.016). High plasma leptin level (adjusted hazard ratio (aHR) = 3.74, and p = 0.011) and leptin receptor (LEPR) mRNA expression (aHR = 3.12, and p = 0.045) were independent risk factors for poor PFS in CP. Inappropriately elevated leptin relative to BMI and its failure to inhibit further weight gain indicate the existence of leptin resistance in patients with CP. Leptin and LEPR were independent predictors for PFS of patients with CP. The leptin/leptin receptors axis may be a potential therapeutic target for obesity in patients with CP.

Effects of Craniotomy and Endoscopic Endonasal Transsphenoidal Surgery on Bodyweight in Adult-Onset Craniopharyngioma: A Single-Center Retrospective Study.

Craniopharyngioma (CP) is a histologically benign tumor with high mortality and morbidity. Although surgical treatment is essential in managing CP, the best surgical approach is debated. A retrospective cohort of 117 patients with adult-onset CP (AOCP) treated between 2018 and 2020 in Beijing Tiantan Hospital was identified and examined. The effects of traditional craniotomy (TC) and endoscopic endonasal transsphenoidal surgery (EETS) on the extent of surgical resection, hypothalamic involvement (HI), postoperative endocrine function, and postoperative weight were compared in the cohort. The cohort comprised 43 males and 74 females, divided into the TC (n = 59) and EETS (n = 58) groups. The EETS group possessed a higher rate of gross total resection (GTR) (adjusted odds ratio (aOR) = 4.08, p = 0.029) and improved HI (aOR = 2.58, p = 0.041) than the TC group. Worse postoperative HI was only observed in the TC group (5 patients). The EETS was associated with fewer adverse hormonal outcomes, including posterior pituitary dysfunction (aOR = 0.386, p = 0.040) and hypopituitarism (aOR = 0.384, p = 0.031). Additionally, multivariate logistic regression analysis confirmed that EETS was related to fewer cases of weight gain >5% (aOR = 0.376, p = 0.034), significant weight change (aOR = 0.379, p = 0.022), and postoperative obesity (aOR = 0.259, p = 0.032). Compared to TC, EETS shows advantages in accomplishing GTR, hypothalamus protection, postoperative endocrine function reservation, and postoperative weight control. These data suggest that the EETS deserves more application in managing patients with AOCP.

Immune infiltration in aggressive papillary craniopharyngioma: High infiltration but low action.

Papillary craniopharyngiomas (PCPs) are biologically benign but clinically aggressive lesions hence affect the quality of life. The expression of inflammatory mediators and regulation of the immune microenvironment in PCPs have not been investigated much. In this study, for the first time, we assessed the immune cell infiltration and immune cell signatures in PCPs by analyzing the bulk-RNA sequencing data and immunohistochemical staining. Additionally, we performed qRT-PCR analysis to detect inflammatory mediators interleukin-1α (IL1A) and interleukin-6 (IL6) in different aggressive groups and then developed the IL1A and IL6 prediction models for defining the degree of hypothalamic invasion. Lastly, we defined differentially expressed genes related to invasiveness and implemented enrichment analysis to them. Our results indicated that PCPs are in a state of high immune infiltration but low action with abundant inflammatory cells. High infiltration of neutrophils may lead a low active immune microenvironment. Furthermore, the high expression level of IL1A and IL6 was positively correlated with the invasion of PCP tumors in the hypothalamus. These findings provide new pathological insights into the underlying mechanism of the immune microenvironment in PCP tumors. Moreover, IL1A and IL6 might serve as potential therapeutic targets for PCP tumors, especially to prevent their invasion into the hypothalamus.

Integrin α6 Indicates a Poor Prognosis of Craniopharyngioma through Bioinformatic Analysis and Experimental Validation.

Background: Craniopharyngioma (CP) is a benign slow-growing tumor. It tends to affect children, and the number of patients is on rise. Considering the high morbidity and mortality of CP, it is urgent and pivotal to identify new biomarkers to uncover the etiology and pathogenesis of CP. Methods: The "limma" package was utilized to calculate the data from the Gene Expression Omnibus (GEO) database. Based on differentially expressed genes (DEGs), gene ontology and pathway analysis were deduced from the DAVID web tool. Further, we constructed a protein-protein interaction (PPI) network. Weighted correlation network analysis (WGCNA) was utilized to build a coexpression network. Finally, Western blotting and survival analysis were performed to examine the expression level of important metabolism-related genes. Results: Three hundred and eighty-four DEGs were identified between normal tissues and CPs from the GSE94349 and GSE26966 datasets. The Venn diagram for DEGs and hub genes in the 'turquoise' module revealed four key genes. Finally, the outcome of the survival analysis suggested that Integrin α6 (ITGA6) significantly affected the overall survival time of the patients with CP. Conclusion: IGTA6, as a metabolism-related molecule, was found to be substantially related to the overall survival of patients with CP.

Feasibility of endoscopic endonasal resection of intrinsic third ventricular craniopharyngioma in adults.

Intrinsic third ventricular craniopharyngiomas (IVCs) are usually considered as a contraindication of endoscopic endonasal approach (EEA). The aim of this study is to evaluate the safety and feasibility of EEA for the resection of IVCs based on MRI topographical diagnosis and surgical findings. We reviewed the data of 22 patients who were diagnosed to be IVCs according to five MRI criteria and underwent surgery through EEA. Sixteen IVCs were resected using endoscopic endonasal infrachiasmatic corridor, five IVCs by using endoscopic endonasal suprachiasmatic trans-lamina terminalis corridor, and one IVC by using both the infrachiasmatic and suprachiasmatic corridors. During the operation, all the 22 cases were verified to be IVCs. Gross total resection was achieved in 21 (95.5%) patients. After surgery, visual improvement was observed in 14 (63.6%) patients, no change in 6 (27.3%) patients, and some deterioration in 2 (9.1%) patients. An improvement in intellectual ability was observed in nine (40.9%) patients, no change in twelve (54.5%) patients, and some deterioration in one (4.5%) patient. Fifteen of the 22 patients (68.2%) developed new endocrinological deficit. One postoperative cerebral spinal fluid leakage occurred. EEA can be used as a safe and efficacious approach for the radical resection of IVCs. The combination of the five MRI criteria may serve as an accurate preoperative diagnostic tool to define the topographical relationships between craniopharyngiomas and the third ventricle. The endoscopic transnasal view from below has the advantage of clarifying the relationship between tumors and the third ventricle floor.