MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to...MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.展开更多
BACKGROUND Neuroendocrine tumors(NET)are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body.Acromegaly,a rare and slowly progressive disorder,usually results from a growth hormone(GH)-s...BACKGROUND Neuroendocrine tumors(NET)are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body.Acromegaly,a rare and slowly progressive disorder,usually results from a growth hormone(GH)-secreting pituitary adenoma.CASE SUMMARY We herein describe a 38-year-old patient who was initially diagnosed with diabetes.During colonoscopy,two bulges were identified and subsequently removed through endoscopic submucosal dissection.Following the surgical intervention,the excised tissue samples were examined and confirmed to be grade 2 NET.^(18)F-ALF-NOTATATE positron emission tomography-computed tomography(PET/CT)and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes,prompting laparoscopic low anterior resection with total mesorectal excision.The patient later returned to the hospital because of hyperglycemia and was found to have facial changes,namely a larger nose,thicker lips,and mandibular prognathism.Laboratory tests and magnetic resonance imaging(MRI)suggested a GH-secreting pituitary adenoma.The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach.Whole-exome sequencing analysis revealed no genetic abnormalities.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION ^(18)F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.展开更多
BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interv...BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interventions utilized among these patients is poorly studied.AIM To evaluate the surgical indications,timing,perioperative precautions and postoperative complications of PAs during pregnancy and to provide comprehensive guidance.METHODS Six patients with PAs who underwent surgical treatment during pregnancy at Peking Union Medical College Hospital between January 1990 and June 2021 were recruited for this study.Another 35 pregnant patients who were profiled in the literature were included in our analysis.RESULTS The 41 enrolled patients had acute symptoms including visual field defects,severe headaches or vision loss that required emergency pituitary surgeries.PA apoplexies were found in 23 patients.The majority of patients(55.9%)underwent surgery in the second trimester of pregnancy.A multidisciplinary team was involved in patient care from the preoperative period through the postpartum period.With the exception of 1 patient who underwent an induced abortion and 1 fetus that died due to a nuchal cord,39 patients delivered successfully.Among them,37 fetuses were healthy until the most recent follow-up.CONCLUSION PA surgery during pregnancy is effective and safe during the second and third trimesters.Pregnant patients requiring emergency PA surgery require multidisciplinary evaluation and healthcare management.展开更多
BACKGROUND Steroid-induced psychosis is a common adverse effect of steroid exposure.Reported cases were mostly related to rheumatologic disease.Despite its high incidence,there is only one case reported related to per...BACKGROUND Steroid-induced psychosis is a common adverse effect of steroid exposure.Reported cases were mostly related to rheumatologic disease.Despite its high incidence,there is only one case reported related to perioperative steroid replacement for pituitary adenoma surgery.This manuscript presents the second case of such and compared the two with the latest literature review of steroidinduced psychosis.CASE SUMMARY This is a case of an adult male with a chief complaint of auditory hallucinations and was referred by Neurosurgery to Psychiatry Out-patient department.He was diagnosed with pituitary adenoma who underwent trans-sphenoid excision of the mass from which steroid exposure led to steroid-induced psychosis.Also,patient had a history of psychiatric illness of severe depressive episode.At the out-patient department,patient was started on antipsychotic,Risperidone,which led to eventual improvement of his symptoms.CONCLUSION The two cases of pituitary adenoma surgery with steroid-induced psychosis had almost similar clinical profile with the latest literature review of steroid-induced psychosis.However,the present case highlights the association of psychiatric illness in predisposing an individual in developing it.Also,this manuscript emphasizes that early recognition of steroid-induced psychosis leads to better prognosis.Multispecialty treatment is vital in the holistic management of the patient with timely referral and close coordination.展开更多
Introduction: in adults, adenomas are the most frequent causes of pituitary tumours. The objective was to characterize its epidemiological and clinical aspects, as well as its therapeutic modalities in Senegal. Method...Introduction: in adults, adenomas are the most frequent causes of pituitary tumours. The objective was to characterize its epidemiological and clinical aspects, as well as its therapeutic modalities in Senegal. Methodology: this was a multicenter, retrospective, descriptive and analytical study carried out from the Senegalese register of pituitary adenomas (2008-2022). Results: 242 patients were collected with an average age of 42.4 ± 13 years and a sex ratio (M/F) of 0.91. The mean consultation time was 19.7 ± 23 months. The circumstances of discovery were pituitary apoplexy (11 cases, 4.54%), tumor syndrome (176 cases, 72.72%), gonadal manifestations (103 cases, 42.56%), dysmorphic syndrome (21 cases, 8.68%), hypercorticism (15 cases, 6.19%). Morphologically, it was a macroadenoma (197 cases, 81.40%), an extensive adenoma (22 cases, 9.10%). The hormonal profile was lactotropic hypersecretion (80 cases, 33.05%), somatotropic (13 cases, 5.39%), corticotropic (14 cases, 5.78%), mixed (9 cases, 3.71%). The factors significantly associated with prolactinoma were young age (p = 0.000), female sex (p = 0.000), long consultation delay (p = 0.000) and microadenoma (p = 0.001). Only arterial hypertension was associated with acromegaly (p = 0.000). We found a significant correlation between Cushing’s disease and microadenomas (p = 0.000). Non-secreting adenomas were significantly associated with advanced age (p = 0.000), long delay in consultation (p = 0.000), male gender (p = 0.000), tumor syndrome (p = 0.001) and macroadenomas (p = 0.000). Pituitary surgery was effective in 173 patients (71.49%) including 166 cases (68.59%) by transphenoidal approach. Postoperative incidents were transient diabetes insipidus in 82 cases (47.39%), cerebrospinal fluid leak (20 cases, 11.56%). Death was observed in 18 patients in the entire series (7.44%). The latter had a tumor syndrome (88.88%), a macroadenoma (83.33%) and had undergone pituitary surgery (72.22%). Conclusion: pituitary pathology has become a reality with clinical and secretory polymorphism. The diagnostic delay explains the predominance of macroadenomas which are sources of pre and post-operative complications.展开更多
Introduction: In the context of pituitary adenoma, bacterial meningitis is a possible complication of surgical or medical treatment. The occurrence of meningitis before any treatment is exceptional, explained by the e...Introduction: In the context of pituitary adenoma, bacterial meningitis is a possible complication of surgical or medical treatment. The occurrence of meningitis before any treatment is exceptional, explained by the existence of an osteomeningeal breach caused by the adenoma whose main symptom is rhinorrhea. Case Report: We report a case of bacterial meningitis complicating a prolactin pituitary macroadenoma. The patient had been referred for jet vomiting in a febrile context preceded by headaches and visual blurring. There was no rhinorrhea. The examination revealed a meningeal syndrome and the diagnosis of acute bacterial meningitis was made. The isolated germ was the pneumococcus. Faced with headaches and visual blurring, a cerebral scan revealed a pituitary macroadenoma and pituitary hormone dosage had shown hyperprolactinemia. The meningitis was sterilized and the prolactinoma was treated with dopaminergic agonists. This allowed the normalization of prolactinemia and the disappearance of symptoms. Conclusion: The pituitary adenoma was complicated by bacterial meningitis without treatment and the presence of a meningeal breach. Hormonal and bacterial treatments have been successful.展开更多
Background: The simultaneous presence of a pituitary adenoma and a meningioma is a rare and underreported condition. The randomly encountered cases need to be reported to further allow our understanding of this collis...Background: The simultaneous presence of a pituitary adenoma and a meningioma is a rare and underreported condition. The randomly encountered cases need to be reported to further allow our understanding of this collision tumors that are still not understood nor fully described. Patients and Method: We report a case of coexisting nonfunctioning pituitary adenoma and a left temporal lobe meningioma revealed by a 1-year history of progressive vision loss and occasional headaches in a 56-year-old woman. Her clinical condition worsened in the last 5 months with ptosis, cavernous sinus syndrome, and ophthalmoplegia of the right eye without papilledema. There was an improvement in the visual symptoms after subtotal resection of both lesions through a right frontotemporal craniotomy. Histology confirmed a collision tumor. The patient was referred for adjuvant treatment with gamma knife radiosurgery. He was doing well and back to his usual duties 6 months later. Conclusion: A gross total or subtotal resection with adjuvant therapy is the gold standard for the surgical management of collision tumors for a favorable patient outcome.展开更多
Objective: To study the relationship between histopathology and clinical prognosis of invasive pituitary adenoma subjected to transsphenoidal surgery. Methods: The enrolled were 82 patients with invasive pituitary ade...Objective: To study the relationship between histopathology and clinical prognosis of invasive pituitary adenoma subjected to transsphenoidal surgery. Methods: The enrolled were 82 patients with invasive pituitary adenomas undergoing transsphenoidal surgery during Jan. 2000 - May 2003 in our department with full MR imaging findings, pathology data and follow-up information. The follow-up duration was 5-30 months. Results: MR imaging findings of invasive pituitary adenoma included: depression of the sellar floor, involvement of sphenoid sinus and cavernous sinus, breakthrough of diaphragma sellae, encasement of internal carotid artery, etc. Pathological examination revealed that the invasion rate of dura in sella turcica was the highest among the structures around tumor. Pituitary adenoma apoplexy was found in 20 cases (24.4%). The total removal rate for PRL-secreting adenomas was significantly lower than that for non-secreting adenomas (P<0.01), but non-, GH-, ACTH-secreting adenomas had no significant differences. The recurrence rate of PRL-secreting adenomas was higher than that of non- and GH-secreting adenomas (P<0.05). Conclusion: Among invasive pituitary adenomas, the therapeutic effects of non-and GH-secreting pituitary adenomas are better than that of PRL-secreting adenomas. Invasive biological behaviors of invasive pituitary adenomas result in radical operation failure and postoperative recurrence.展开更多
Objective: To investigate the predictability of MRI and the possiblebiological markers of cavernous sinus invasion of pituitary adenomas associated with fourphenomenas: angiogenesis, cell proliferation, apoptosis and ...Objective: To investigate the predictability of MRI and the possiblebiological markers of cavernous sinus invasion of pituitary adenomas associated with fourphenomenas: angiogenesis, cell proliferation, apoptosis and matrix metalloproteinase. Methods: Weevaluated 45 patients with pituitary adenoma according to the MRI, surgical findings and theimmunohistochemistry staining of tumor tissues. Results: The results have shown that the sensitivityof MRI for predicting cavernous sinus invasion in this prospective study was 60%, its specificity85%, its positive predictive value 83.33%, negative predictive value 62.96%. 45 specimens ofpituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, Bcl-2, nm23 and MMP-9immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. Theresults have shown that MVD of invasive pituitary adenomas was significantly higher than that ofnoninvasive (P 【 0.001). There was an association between the invasion of pituitary adenomas andKi-67 LI (P = 0.039) or the expression of VEGF (P 【 0.001) and MMP-9 (P 【 0.001). But c-myc LI andBcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 versus P =0.201). On the other hand, there is an inverse relationship between nm23 expression and tumorinvasion (P 【 0.001). Conclusion: Parasellar extension of pituitary adenomas through the medial wallof the cavernous sinus is diagnosed at surgery, and with sensitive gadolinium-enhanced MRI, itsextent can be partly determined by radiology. Although our study has shown that MVD and theexpression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,they are lack of specificity. These markers can only provide some useful information.展开更多
Three human leucine-rich repeats and immunoglobulin-like domains （LRIG） genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The ...Three human leucine-rich repeats and immunoglobulin-like domains （LRIG） genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor. Real-time reverse transcription-polymerase chain reaction （RT-PCR） is a recently developed technique for quantitative assessment of specific RNA levels. In the current study, it was demonstrated that LRIG1-3 and EGFR mRNA was detected in human pituitary adenoma cell lines and a normal pituitary sample, with differences in the expression levels. Compared to the normal pituitary samples, the expression of LRIG1-3 in HP75 cell line was lower, but the expression of EGFR in HP75 cell line was higher. The results are consistent with LRIG1-3 being tumour suppressor genes, and LRIG genes decreasing the expression of EGFR. The ratio of EGFR/LRIGl was increased at least 13-fold in HP75 cells compared with the normal pituitary cells, which was also the case for the ratio of EGFR/LRIG2 （14-fold increase in HP75） and EGFR/LRIG3 （11-fold increase in HP75）. Further studies were needed to elucidate the explicit role of LRIG genes as negative regulators of oncogenesis in human pituitary adenoma.展开更多
BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and micro...BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and microscopic transsphenoidal approaches have been widely used in the resection of nonfunctional pituitary adenomas. However, the clinical efficacy in neuroendoscopic and microscopic surgery is still controversial. AIM To explore the clinical efficacy of neuroendoscopic and microscopic transsphenoidal approach for resection of nonfunctional pituitary adenomas. METHODS We retrospectively analyzed 251 patients with nonfunctional pituitary adenomas;138 underwent neuroendoscopic surgery via transsphenoidal approach, and 113 underwent microscopic surgery via transsphenoidal approach between July 2010 and September 2015. All patients were followed up for > 6 mo. Gender, age, course of disease, tumor diameter, tumor location, and percentage of patients with headache, visual impairment, sexual dysfunction, and menstrual disorders were contrasted between the two groups to compare the difference of preoperative data. Cure rate, symptom improvement rate, recurrence rate, the postoperative hospital stay, operating time, intraoperative blood loss, and the incidence of postoperative complications were compared in order to evaluate the advantages and disadvantages of neuroendoscopic and microscopic surgery.RESULTS There was no significant difference in cure rate, symptom improvement rate, and recurrence rate between neuroendoscopy group and microscopy group (82.6% vs 85.8%, P > 0.05;90.6% vs 93.8%, P > 0.05;5.1% vs 9.7%, P > 0.05). In the neuroendoscopy group, the postoperative hospital stay was 8.4 ± 0.6 d;operating time was 167.2 ± 9.6 min;intraoperative blood loss was 83.4 ± 9.3 mL, and the rates of diabetes insipidus and electrolyte imbalance were 4.3% and 8.0%, respectively. The corresponding results in the microscopic group were 11.2 ± 0.6 d, 199.7 ± 9.3 min, 138.8 ± 13.6 mL, and 32.7% and 20.4%, respectively. There were significant differences in postoperative hospital stay, operating time, intraoperative blood loss, and the rates of diabetes insipidus and electrolyte imbalance between the two groups (P < 0.05). CONCLUSION Neuroendoscopic and microscopic transsphenoidal approaches have similar clinical efficacy for the resection of nonfunctional pituitary adenomas. Neuroendoscopic surgery reduces operating time, intraoperative bleeding, postoperative recovery, and complications.展开更多
Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituit...Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma （21 invasive and 14 non-invasive） patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas （IPA） was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas （nlPA） （P〈O.05）. Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas （P〈O.05）. In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.展开更多
The Leucine-rich repeats and immunoglobulin-like domains-2（LRIG2） gene expression in pituitary adenoma and its correlation with tumor invasiveness were studied.The expression of LRIG2 mRNA and protein in human pitui...The Leucine-rich repeats and immunoglobulin-like domains-2（LRIG2） gene expression in pituitary adenoma and its correlation with tumor invasiveness were studied.The expression of LRIG2 mRNA and protein in human pituitary adenoma obtained surgically was detected by RT-PCR（39 cases） and immunohistochemical staining（30 cases）.It was found that LRIG2 was mostly localized at the nucleus of the pituitary adenoma cells.Its expression was significantly higher in the invasive cases than in the non-invasive cases.LRIG2 protein was positive in 14 cases out of 21 cases of invasive adenoma,but only 2 cases were positive in 9 cases of non-invasive adenoma.The positive expression rate of LRIG2 mRNA was 91.3% in invasive cases（total 23 cases） and 62.5% in non-invasive cases（total 16 cases）,respectively.LRIG2 gene is overexpressed in invasive pituitary adenoma.It may play an important role in pituitary adenoma invasiveness and further studies are necessary to elucidate the mechanism under this phenomenon.展开更多
Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acrome...Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.展开更多
Objective To evaluate magnetic resonance imaging （MRI） characteristics and surgical results of adrenocorticotropin （ACTH） -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI po...Objective To evaluate magnetic resonance imaging （MRI） characteristics and surgical results of adrenocorticotropin （ACTH） -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confn＇med Cushing＇s disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid （Gd-DTPA） on a 1. 5 Tesla MR/scanner, and dynamic enhanced MR/was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed. Results Preoperative MR/revealed normal results in 41 （ 15.4% ） cases, microadenoma in 179 （67. 3% ）, macroadenoma in 42 （ 15.8% ）, and huge adenoma in 4 （ 1.5% ）. Pituitary apoplexy was found in 13 （4.9%） cases. Positive rate of ACTH-secreting adenomas was 84.6% （225/266） on MR/scans, and that of small microadenomas was 87.2% （34/39） on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing＇s disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6. 4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results （90% vs. 87. 8%, P =0. 904）. Conclusions Enhanced coronal pituitary MR/ is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MR/may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MR/results indicating presence or absence of microadenoma.展开更多
Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of ...Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor（EGFR） can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1（ LRIG1）, a negative mediated gene of Erb B receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.展开更多
The latest edition of the WHO classification of the central nervous system was published in 2021.This review summarizes the major revisions to the classification of anterior pituitary tumors.The most important revisio...The latest edition of the WHO classification of the central nervous system was published in 2021.This review summarizes the major revisions to the classification of anterior pituitary tumors.The most important revision involves preferring the terminology of pituitary neuroendocrine tumor(PitNET),even though the terminology of pituitary adenoma(PA)still can be used according to this WHO classification compared to the previous one.Moreover,immunohistochemistry(IHC)examination of pituitary-specific transcription factors(TFs),including PIT1,TPIT,SF-1,GATA2/3,and ERα,is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups.However,TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages,which includes unclassified plurihormonal(PH)tumors and null cell(NC)tumors in this edition.The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors.However,due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA,the application of this new classification system in practice should be further evaluated and validated.Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery,this classification system offers no additional help for neurosurgeons in clinical practice,especially in determining the treatment strategies.Therefore,it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis,as well as pathological diagnosis,thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.展开更多
AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visua...AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans-sphenoidal surgery. Ophthalmologic evaluation, best -corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23 +/- 1.29y. Ninety -three patients were female and 108 were male. The mean tumor volume was 14.36 +/- 6.23 cm(3). The mean duration of preoperative symptoms was 11.50 +/- 0.88mo. Mean preoperative MD was -17.50 +/- 0.82 dB. Mean Preoperative visual acuity was 0.64 +/- 0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/Ki-67.展开更多
Objective To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas(NF-PAs).Methods The exosomal RNAs were extracted from serum of patients with invasive NF-PA(INF-PA)or no...Objective To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas(NF-PAs).Methods The exosomal RNAs were extracted from serum of patients with invasive NF-PA(INF-PA)or noninvasive NF-PA(NNF-PA).Droplet digital PCR was adapted to detect the mRNA expression of candidate genes related to tumor progression or invasion,such as cyclin dependent kinase 6(CDK6),ras homolog family member U(RHOU),and spire type actin nucleation factor 2(SPIRE2).Student’s t-test was used to analyze the statistical difference in the mRNA expression of candidate genes between the two groups.Receiver operating characteristic(ROC)curve was used to establish a model for predicting the invasiveness of NF-PAs.The accuracy,sensitivity,specificity and precision of the model were then obtained to evaluate the diagnostic performance.Results CDK6(0.2600±0.0912 vs.0.1789±0.0628,t=3.431,P=0.0013)and RHOU mRNA expressions(0.2696±0.1118 vs.0.1788±0.0857,t=2.946,P=0.0052)were upregulated in INF-PAs patients’serum exosomes as compared to NNF-PAs.For CDK6,the area under the ROC curve(AUC)was 0.772(95%CI:0.600-0.943,P=0.005),the accuracy,sensitivity,specificity and precision were 77.27%,83.33%,75.00%and 55.56%to predict the invasiveness of NF-PAs.For RHOU,the AUC was 0.757(95%CI:0.599-0.915,P=0.007),the accuracy,sensitivity,specificity and precision were 72.73%,83.33%,68.75%and 50.00%.In addition,the mRNA levels of CDK6 and RHOU in serum exosomes were significantly positively correlated(r=0.935,P<0.001).After combination of the cut-off scores of the two genes,the accuracy,sensitivity,specificity and precision were 81.82%,83.33%,81.25%and 62.50%.Conclusions CDK6 and RHOU mRNA in serum exosomes can be used as markers for predicting invasiveness of NF-PAs.Combination of the two genes performs better in distinguishing INF-PAs from NNF-PAs.These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs,and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment.展开更多
To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was d...To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.展开更多
基金supported by Correlation between RECK and GH-type pituitary adenomas(No.21JR11RE027).
文摘MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.
文摘BACKGROUND Neuroendocrine tumors(NET)are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body.Acromegaly,a rare and slowly progressive disorder,usually results from a growth hormone(GH)-secreting pituitary adenoma.CASE SUMMARY We herein describe a 38-year-old patient who was initially diagnosed with diabetes.During colonoscopy,two bulges were identified and subsequently removed through endoscopic submucosal dissection.Following the surgical intervention,the excised tissue samples were examined and confirmed to be grade 2 NET.^(18)F-ALF-NOTATATE positron emission tomography-computed tomography(PET/CT)and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes,prompting laparoscopic low anterior resection with total mesorectal excision.The patient later returned to the hospital because of hyperglycemia and was found to have facial changes,namely a larger nose,thicker lips,and mandibular prognathism.Laboratory tests and magnetic resonance imaging(MRI)suggested a GH-secreting pituitary adenoma.The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach.Whole-exome sequencing analysis revealed no genetic abnormalities.The patient recovered well with no evidence of recurrence during follow-up.CONCLUSION ^(18)F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.
文摘BACKGROUND Although conservative treatment is typically recommended for pregnant patients with pituitary adenoma(PA),surgical treatment is occasionally necessary for those with acute symptoms.Currently,surgical interventions utilized among these patients is poorly studied.AIM To evaluate the surgical indications,timing,perioperative precautions and postoperative complications of PAs during pregnancy and to provide comprehensive guidance.METHODS Six patients with PAs who underwent surgical treatment during pregnancy at Peking Union Medical College Hospital between January 1990 and June 2021 were recruited for this study.Another 35 pregnant patients who were profiled in the literature were included in our analysis.RESULTS The 41 enrolled patients had acute symptoms including visual field defects,severe headaches or vision loss that required emergency pituitary surgeries.PA apoplexies were found in 23 patients.The majority of patients(55.9%)underwent surgery in the second trimester of pregnancy.A multidisciplinary team was involved in patient care from the preoperative period through the postpartum period.With the exception of 1 patient who underwent an induced abortion and 1 fetus that died due to a nuchal cord,39 patients delivered successfully.Among them,37 fetuses were healthy until the most recent follow-up.CONCLUSION PA surgery during pregnancy is effective and safe during the second and third trimesters.Pregnant patients requiring emergency PA surgery require multidisciplinary evaluation and healthcare management.
文摘BACKGROUND Steroid-induced psychosis is a common adverse effect of steroid exposure.Reported cases were mostly related to rheumatologic disease.Despite its high incidence,there is only one case reported related to perioperative steroid replacement for pituitary adenoma surgery.This manuscript presents the second case of such and compared the two with the latest literature review of steroidinduced psychosis.CASE SUMMARY This is a case of an adult male with a chief complaint of auditory hallucinations and was referred by Neurosurgery to Psychiatry Out-patient department.He was diagnosed with pituitary adenoma who underwent trans-sphenoid excision of the mass from which steroid exposure led to steroid-induced psychosis.Also,patient had a history of psychiatric illness of severe depressive episode.At the out-patient department,patient was started on antipsychotic,Risperidone,which led to eventual improvement of his symptoms.CONCLUSION The two cases of pituitary adenoma surgery with steroid-induced psychosis had almost similar clinical profile with the latest literature review of steroid-induced psychosis.However,the present case highlights the association of psychiatric illness in predisposing an individual in developing it.Also,this manuscript emphasizes that early recognition of steroid-induced psychosis leads to better prognosis.Multispecialty treatment is vital in the holistic management of the patient with timely referral and close coordination.
文摘Introduction: in adults, adenomas are the most frequent causes of pituitary tumours. The objective was to characterize its epidemiological and clinical aspects, as well as its therapeutic modalities in Senegal. Methodology: this was a multicenter, retrospective, descriptive and analytical study carried out from the Senegalese register of pituitary adenomas (2008-2022). Results: 242 patients were collected with an average age of 42.4 ± 13 years and a sex ratio (M/F) of 0.91. The mean consultation time was 19.7 ± 23 months. The circumstances of discovery were pituitary apoplexy (11 cases, 4.54%), tumor syndrome (176 cases, 72.72%), gonadal manifestations (103 cases, 42.56%), dysmorphic syndrome (21 cases, 8.68%), hypercorticism (15 cases, 6.19%). Morphologically, it was a macroadenoma (197 cases, 81.40%), an extensive adenoma (22 cases, 9.10%). The hormonal profile was lactotropic hypersecretion (80 cases, 33.05%), somatotropic (13 cases, 5.39%), corticotropic (14 cases, 5.78%), mixed (9 cases, 3.71%). The factors significantly associated with prolactinoma were young age (p = 0.000), female sex (p = 0.000), long consultation delay (p = 0.000) and microadenoma (p = 0.001). Only arterial hypertension was associated with acromegaly (p = 0.000). We found a significant correlation between Cushing’s disease and microadenomas (p = 0.000). Non-secreting adenomas were significantly associated with advanced age (p = 0.000), long delay in consultation (p = 0.000), male gender (p = 0.000), tumor syndrome (p = 0.001) and macroadenomas (p = 0.000). Pituitary surgery was effective in 173 patients (71.49%) including 166 cases (68.59%) by transphenoidal approach. Postoperative incidents were transient diabetes insipidus in 82 cases (47.39%), cerebrospinal fluid leak (20 cases, 11.56%). Death was observed in 18 patients in the entire series (7.44%). The latter had a tumor syndrome (88.88%), a macroadenoma (83.33%) and had undergone pituitary surgery (72.22%). Conclusion: pituitary pathology has become a reality with clinical and secretory polymorphism. The diagnostic delay explains the predominance of macroadenomas which are sources of pre and post-operative complications.
文摘Introduction: In the context of pituitary adenoma, bacterial meningitis is a possible complication of surgical or medical treatment. The occurrence of meningitis before any treatment is exceptional, explained by the existence of an osteomeningeal breach caused by the adenoma whose main symptom is rhinorrhea. Case Report: We report a case of bacterial meningitis complicating a prolactin pituitary macroadenoma. The patient had been referred for jet vomiting in a febrile context preceded by headaches and visual blurring. There was no rhinorrhea. The examination revealed a meningeal syndrome and the diagnosis of acute bacterial meningitis was made. The isolated germ was the pneumococcus. Faced with headaches and visual blurring, a cerebral scan revealed a pituitary macroadenoma and pituitary hormone dosage had shown hyperprolactinemia. The meningitis was sterilized and the prolactinoma was treated with dopaminergic agonists. This allowed the normalization of prolactinemia and the disappearance of symptoms. Conclusion: The pituitary adenoma was complicated by bacterial meningitis without treatment and the presence of a meningeal breach. Hormonal and bacterial treatments have been successful.
文摘Background: The simultaneous presence of a pituitary adenoma and a meningioma is a rare and underreported condition. The randomly encountered cases need to be reported to further allow our understanding of this collision tumors that are still not understood nor fully described. Patients and Method: We report a case of coexisting nonfunctioning pituitary adenoma and a left temporal lobe meningioma revealed by a 1-year history of progressive vision loss and occasional headaches in a 56-year-old woman. Her clinical condition worsened in the last 5 months with ptosis, cavernous sinus syndrome, and ophthalmoplegia of the right eye without papilledema. There was an improvement in the visual symptoms after subtotal resection of both lesions through a right frontotemporal craniotomy. Histology confirmed a collision tumor. The patient was referred for adjuvant treatment with gamma knife radiosurgery. He was doing well and back to his usual duties 6 months later. Conclusion: A gross total or subtotal resection with adjuvant therapy is the gold standard for the surgical management of collision tumors for a favorable patient outcome.
基金This project was supported by a grant from the National Natural Science Foundation of China (No. 39670736).
文摘Objective: To study the relationship between histopathology and clinical prognosis of invasive pituitary adenoma subjected to transsphenoidal surgery. Methods: The enrolled were 82 patients with invasive pituitary adenomas undergoing transsphenoidal surgery during Jan. 2000 - May 2003 in our department with full MR imaging findings, pathology data and follow-up information. The follow-up duration was 5-30 months. Results: MR imaging findings of invasive pituitary adenoma included: depression of the sellar floor, involvement of sphenoid sinus and cavernous sinus, breakthrough of diaphragma sellae, encasement of internal carotid artery, etc. Pathological examination revealed that the invasion rate of dura in sella turcica was the highest among the structures around tumor. Pituitary adenoma apoplexy was found in 20 cases (24.4%). The total removal rate for PRL-secreting adenomas was significantly lower than that for non-secreting adenomas (P<0.01), but non-, GH-, ACTH-secreting adenomas had no significant differences. The recurrence rate of PRL-secreting adenomas was higher than that of non- and GH-secreting adenomas (P<0.05). Conclusion: Among invasive pituitary adenomas, the therapeutic effects of non-and GH-secreting pituitary adenomas are better than that of PRL-secreting adenomas. Invasive biological behaviors of invasive pituitary adenomas result in radical operation failure and postoperative recurrence.
文摘Objective: To investigate the predictability of MRI and the possiblebiological markers of cavernous sinus invasion of pituitary adenomas associated with fourphenomenas: angiogenesis, cell proliferation, apoptosis and matrix metalloproteinase. Methods: Weevaluated 45 patients with pituitary adenoma according to the MRI, surgical findings and theimmunohistochemistry staining of tumor tissues. Results: The results have shown that the sensitivityof MRI for predicting cavernous sinus invasion in this prospective study was 60%, its specificity85%, its positive predictive value 83.33%, negative predictive value 62.96%. 45 specimens ofpituitary adenomas were analyzed for expression of F8, VEGF, Ki-67, c-myc, Bcl-2, nm23 and MMP-9immunoreactivity using immunoperoxidase staining. MVD was assessed using F8-related antigen. Theresults have shown that MVD of invasive pituitary adenomas was significantly higher than that ofnoninvasive (P 【 0.001). There was an association between the invasion of pituitary adenomas andKi-67 LI (P = 0.039) or the expression of VEGF (P 【 0.001) and MMP-9 (P 【 0.001). But c-myc LI andBcl-2 expression have no association with invasiveness of pituitary adenomas (P = 0.061 versus P =0.201). On the other hand, there is an inverse relationship between nm23 expression and tumorinvasion (P 【 0.001). Conclusion: Parasellar extension of pituitary adenomas through the medial wallof the cavernous sinus is diagnosed at surgery, and with sensitive gadolinium-enhanced MRI, itsextent can be partly determined by radiology. Although our study has shown that MVD and theexpression of VEGF, Ki-67, nm23 and MMP-9 have associations with invasiveness of pituitary adenomas,they are lack of specificity. These markers can only provide some useful information.
文摘Three human leucine-rich repeats and immunoglobulin-like domains （LRIG） genes and proteins, named LRIG1-3, has been previously characterized and it was proposed that they may act as suppressors of tumor growth. The LRIG1 protein can inhibit the growth of tumors of glial cells and the down-regulation of the LRIG1 gene may be involved in the development and progression of the tumor. Real-time reverse transcription-polymerase chain reaction （RT-PCR） is a recently developed technique for quantitative assessment of specific RNA levels. In the current study, it was demonstrated that LRIG1-3 and EGFR mRNA was detected in human pituitary adenoma cell lines and a normal pituitary sample, with differences in the expression levels. Compared to the normal pituitary samples, the expression of LRIG1-3 in HP75 cell line was lower, but the expression of EGFR in HP75 cell line was higher. The results are consistent with LRIG1-3 being tumour suppressor genes, and LRIG genes decreasing the expression of EGFR. The ratio of EGFR/LRIGl was increased at least 13-fold in HP75 cells compared with the normal pituitary cells, which was also the case for the ratio of EGFR/LRIG2 （14-fold increase in HP75） and EGFR/LRIG3 （11-fold increase in HP75）. Further studies were needed to elucidate the explicit role of LRIG genes as negative regulators of oncogenesis in human pituitary adenoma.
文摘BACKGROUND Nonfunctional pituitary adenoma is a common type of pituitary adenoma, which can lead to headache, visual field disturbance, and cranial nerve damage due to increased tumor volume. Neuroendoscopic and microscopic transsphenoidal approaches have been widely used in the resection of nonfunctional pituitary adenomas. However, the clinical efficacy in neuroendoscopic and microscopic surgery is still controversial. AIM To explore the clinical efficacy of neuroendoscopic and microscopic transsphenoidal approach for resection of nonfunctional pituitary adenomas. METHODS We retrospectively analyzed 251 patients with nonfunctional pituitary adenomas;138 underwent neuroendoscopic surgery via transsphenoidal approach, and 113 underwent microscopic surgery via transsphenoidal approach between July 2010 and September 2015. All patients were followed up for > 6 mo. Gender, age, course of disease, tumor diameter, tumor location, and percentage of patients with headache, visual impairment, sexual dysfunction, and menstrual disorders were contrasted between the two groups to compare the difference of preoperative data. Cure rate, symptom improvement rate, recurrence rate, the postoperative hospital stay, operating time, intraoperative blood loss, and the incidence of postoperative complications were compared in order to evaluate the advantages and disadvantages of neuroendoscopic and microscopic surgery.RESULTS There was no significant difference in cure rate, symptom improvement rate, and recurrence rate between neuroendoscopy group and microscopy group (82.6% vs 85.8%, P > 0.05;90.6% vs 93.8%, P > 0.05;5.1% vs 9.7%, P > 0.05). In the neuroendoscopy group, the postoperative hospital stay was 8.4 ± 0.6 d;operating time was 167.2 ± 9.6 min;intraoperative blood loss was 83.4 ± 9.3 mL, and the rates of diabetes insipidus and electrolyte imbalance were 4.3% and 8.0%, respectively. The corresponding results in the microscopic group were 11.2 ± 0.6 d, 199.7 ± 9.3 min, 138.8 ± 13.6 mL, and 32.7% and 20.4%, respectively. There were significant differences in postoperative hospital stay, operating time, intraoperative blood loss, and the rates of diabetes insipidus and electrolyte imbalance between the two groups (P < 0.05). CONCLUSION Neuroendoscopic and microscopic transsphenoidal approaches have similar clinical efficacy for the resection of nonfunctional pituitary adenomas. Neuroendoscopic surgery reduces operating time, intraoperative bleeding, postoperative recovery, and complications.
基金supported by the key program for clinical research foundation of PUMC Hospital(Grant No.200611)
文摘Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma （21 invasive and 14 non-invasive） patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4- and CXCL12-positive cells from invasive pituitary adenomas （IPA） was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas （nlPA） （P〈O.05）. Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas （P〈O.05）. In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.
文摘The Leucine-rich repeats and immunoglobulin-like domains-2（LRIG2） gene expression in pituitary adenoma and its correlation with tumor invasiveness were studied.The expression of LRIG2 mRNA and protein in human pituitary adenoma obtained surgically was detected by RT-PCR（39 cases） and immunohistochemical staining（30 cases）.It was found that LRIG2 was mostly localized at the nucleus of the pituitary adenoma cells.Its expression was significantly higher in the invasive cases than in the non-invasive cases.LRIG2 protein was positive in 14 cases out of 21 cases of invasive adenoma,but only 2 cases were positive in 9 cases of non-invasive adenoma.The positive expression rate of LRIG2 mRNA was 91.3% in invasive cases（total 23 cases） and 62.5% in non-invasive cases（total 16 cases）,respectively.LRIG2 gene is overexpressed in invasive pituitary adenoma.It may play an important role in pituitary adenoma invasiveness and further studies are necessary to elucidate the mechanism under this phenomenon.
文摘Dopamine agonists effectively reduce the secretion of prolactin (PRL) in the great majority of prolactinomas and reduce the bulk of the adenomas, as well as have partial therapeutic effect on some patients with acromegaly. The inhibitory effect of bromocriptine (BC), a dopamine agonist, on growth hormone (GH) and PRL secretion of dispersed cells from the pituitary adenomas of 16 cases of acromegaly, which secret GH and PRL simultaneously, were evaluated in vitro. The significant inhibitory effects of BC on PRL secretion were found in 12 cases. It was also found that PRL secretion was strongly inhibited when GH was suppressed; on the contrary, when GH secretion was not suppressed, the production of PRL was not or weakly inhibited. The exact mechanism of the effects is nuclear so far. It is necessary to investigate, at molecular level, the etiology of GH-PRL adenomas and its response to therapeutic agents.
文摘Objective To evaluate magnetic resonance imaging （MRI） characteristics and surgical results of adrenocorticotropin （ACTH） -secreting pituitary adenomas. Methods MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confn＇med Cushing＇s disease were analyzed retrospectively. All patients underwent thin-section sagittal and coronal scans of the pituitary gland before and after administration of gadolinium-diethylene triamine pentaacetic acid （Gd-DTPA） on a 1. 5 Tesla MR/scanner, and dynamic enhanced MR/was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed. Results Preoperative MR/revealed normal results in 41 （ 15.4% ） cases, microadenoma in 179 （67. 3% ）, macroadenoma in 42 （ 15.8% ）, and huge adenoma in 4 （ 1.5% ）. Pituitary apoplexy was found in 13 （4.9%） cases. Positive rate of ACTH-secreting adenomas was 84.6% （225/266） on MR/scans, and that of small microadenomas was 87.2% （34/39） on dynamic enhanced MRI scans. Preoperative endocrinological tests of 199 cases supported the diagnosis of typical Cushing＇s disease, while the other 67 cases had atypical endocrinological results. The endocrinological cure rate, remission rate, and inefficacy rate were 85.7%, 7.9%, and 6. 4%, respectively. There was no difference in the initial endocrinological cure rate between the patients with positive and normal MRI results （90% vs. 87. 8%, P =0. 904）. Conclusions Enhanced coronal pituitary MR/ is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MR/may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MR/results indicating presence or absence of microadenoma.
基金supported by grants from the National Natural Science Foundation of China(No.81560412)Jiangxi Provincial Health Development Planning Commission Project(No.20141065)Jiangxi Provincial Natural Science Foundation of China(No.20152BCB24009 and No.20151BDH80009)
文摘Pituitary adenomas（PAs） are well known as a common intracranial benign tumor, and a portion of PAs are refractory to current therapeutic methods. Erb B receptors family signaling pathway regulates the expression of PAs activation associated gene. Inhibition of epidermal growth factor receptor（EGFR） can inhibit proliferation of PAs. Leucine-rich repeats and immunoglobulin-like domains protein 1（ LRIG1）, a negative mediated gene of Erb B receptors family, plays a role in many tumors. However, there are seldom researches about the functional role of LRIG1 in PAs. The aim of this study is to explore the potential effect of LRIG1 and its regulating mechanism in PAs. First, we investigated the role of LRIG1 in cell migration, invasion of PAs with transfected LRIG1 or control. Then, we explored its impact on cell proliferation and apoptosis of PAs in vivo. To study the regulating mechanism of LRIG1, we examined the expression of molecular factor of PI3K/AKT and Ras/Raf/ERK pathway using Western blotting in vitro and RT-PCR in vitro and in vivo. It was found that LRIG1 over-expression inhibited cell migration, invasion and proliferation, and promoted apoptosis of PAs in vivo and in vitro. Furthermore, LRIG1 suppressed the expression of signaling of PI3K/AKT and Ras/Raf/ERK pathways in PAs. LRIG1, as a negative mediated gene of tumor, can inhibit biological function of PAs via inhibiting PI3K/AKT and Ras/Raf/ERK pathways, and it might be a new target for gene therapy of PAs.
文摘The latest edition of the WHO classification of the central nervous system was published in 2021.This review summarizes the major revisions to the classification of anterior pituitary tumors.The most important revision involves preferring the terminology of pituitary neuroendocrine tumor(PitNET),even though the terminology of pituitary adenoma(PA)still can be used according to this WHO classification compared to the previous one.Moreover,immunohistochemistry(IHC)examination of pituitary-specific transcription factors(TFs),including PIT1,TPIT,SF-1,GATA2/3,and ERα,is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups.However,TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages,which includes unclassified plurihormonal(PH)tumors and null cell(NC)tumors in this edition.The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors.However,due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA,the application of this new classification system in practice should be further evaluated and validated.Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery,this classification system offers no additional help for neurosurgeons in clinical practice,especially in determining the treatment strategies.Therefore,it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis,as well as pathological diagnosis,thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.
文摘AIM: To investigate the influencing factors of visual field improvement after trans-sphenoidal resection of pituitary macroadenomas. METHODS: This retrospective cohort study included 201 patients (366 eyes) with visual field defect induced by pituitary macroadenomas. All of them were treated with trans-sphenoidal surgery. Ophthalmologic evaluation, best -corrected visual acuity (BCVA), and visual field examination were performed before and 3mo after surgery. BCVA, visual field defect index mean deviation (MD), duration of symptoms, age, sex, and volume of tumors were compared. Expression of vascular endothelial growth factor (VEGF) and Ki-67 of tumor tissue were detected by immunohistochemical technique. RESULTS: The mean age of patients was 44.23 +/- 1.29y. Ninety -three patients were female and 108 were male. The mean tumor volume was 14.36 +/- 6.23 cm(3). The mean duration of preoperative symptoms was 11.50 +/- 0.88mo. Mean preoperative MD was -17.50 +/- 0.82 dB. Mean Preoperative visual acuity was 0.64 +/- 0.04. Postoperative visual field improved in 270 (73.77%) eyes, unchanged in 96 (26.23%) eyes. Multivariate logistic regression displayed that the factors independently influencing visual field improvement were young age (OR=1.71, 95%CI: 1.325-2.387, P=0.013), low preoperative MD absolute value (OR=1.277, 95%CI: 1.205-1.355, P<0.001), small volume of tumor (OR=1.458, 95%CI: 1.060-4.289, P<0.001), low expression of VEGF in tumor tissue (OR=1.554, 95%CI: 1.089-2.457, P=0.022), and low expression of Ki-67 in tumor tissue (OR=1.552, 95%CI: 1.161-2.847, P=0.026). CONCLUSION: After pituitary macroadenomas trans sphenoidal resection, the independent influencing factors of the visual fields recovery were low preoperative MD absolute value, young age, small volume of tumor, and expression levels of VEGF/Ki-67.
基金Supported by the National Natural Science Foundation of China(31725013)the CAMS Innovation Fund for Medical Sciences(2017-I2M-3-009)the Beijing Nova Program(Z181100006218003)
文摘Objective To explore circulating biomarkers for screening the invasiveness of non-functioning pituitary adenomas(NF-PAs).Methods The exosomal RNAs were extracted from serum of patients with invasive NF-PA(INF-PA)or noninvasive NF-PA(NNF-PA).Droplet digital PCR was adapted to detect the mRNA expression of candidate genes related to tumor progression or invasion,such as cyclin dependent kinase 6(CDK6),ras homolog family member U(RHOU),and spire type actin nucleation factor 2(SPIRE2).Student’s t-test was used to analyze the statistical difference in the mRNA expression of candidate genes between the two groups.Receiver operating characteristic(ROC)curve was used to establish a model for predicting the invasiveness of NF-PAs.The accuracy,sensitivity,specificity and precision of the model were then obtained to evaluate the diagnostic performance.Results CDK6(0.2600±0.0912 vs.0.1789±0.0628,t=3.431,P=0.0013)and RHOU mRNA expressions(0.2696±0.1118 vs.0.1788±0.0857,t=2.946,P=0.0052)were upregulated in INF-PAs patients’serum exosomes as compared to NNF-PAs.For CDK6,the area under the ROC curve(AUC)was 0.772(95%CI:0.600-0.943,P=0.005),the accuracy,sensitivity,specificity and precision were 77.27%,83.33%,75.00%and 55.56%to predict the invasiveness of NF-PAs.For RHOU,the AUC was 0.757(95%CI:0.599-0.915,P=0.007),the accuracy,sensitivity,specificity and precision were 72.73%,83.33%,68.75%and 50.00%.In addition,the mRNA levels of CDK6 and RHOU in serum exosomes were significantly positively correlated(r=0.935,P<0.001).After combination of the cut-off scores of the two genes,the accuracy,sensitivity,specificity and precision were 81.82%,83.33%,81.25%and 62.50%.Conclusions CDK6 and RHOU mRNA in serum exosomes can be used as markers for predicting invasiveness of NF-PAs.Combination of the two genes performs better in distinguishing INF-PAs from NNF-PAs.These results indicate CDK6 and RHOU play important roles in the invasiveness of NF-PAs,and the established diagnostic method is valuable for directing the clinical screening and postoperative treatment.
文摘To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the periph-eral blood in development, invasiveness, apoplexy of each type of pituitary tumor. Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke’s pouch, 18 pituitary hyperplasia, 161 pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 hea-lthy controls. Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carci-noma, the sEGFR level was 188.92 ± 32.62, 209.83 ± 19.01, 333.20 ± 69.33, 405.85 ± 37.38, and 617.45 fmol/mL indepen-dently. They were all significantly higher than patients with pituitary Rathke’s pouch (156.78 ± 18.24 fmol/mL, P < 0.001) and healthy control group (159.11 ± 40.50 fmol/mL, P < 0.05). The sEGFR level in pituitary carcinoma was higher than pi-tuitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adeno-mas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P < 0.001). Furthermore, in patients with pituitary ACTH-secreting microadenomas, the serum sEGFR levels in invasiveness (295.00 ± 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 ± 16.4 fmol/mL, P < 0.05). In pati-ents with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 ± 28.50, 399.25 ± 30.10, 386.00 ± 13.08, and 369.25 ± 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 ± 63.49, 300.64 ± 47.57, 297.00 ± 61.93, and 269.30 ± 25.68 fmol/mL) respectively (P < 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 ± 35.94, 409.50 ± 69.14, and 417.50 ± 44.13 fmol/mL) and non-invasiveness (386.00 ± 49.64, 417.50 ± 44.03, and 409.51 ± 35.17 fmol/mL) (P > 0.05). In patients with pituitary large adeno-mas, the sEGFR levels in pituitary apoplexy (377.48 ± 39.18 fmol/mL) was higher than that in non-pituitary apoplexy (343.18 ± 68.17 fmol/mL, P > 0.05). Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differen-tiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.
