Advances in the mechanism of action of metformin in pituitary tumors

Pituitary tumors are common intracranial tumors,but when faced with drugresistant or aggressive tumors,existing medical measures may not provide good control,leading to progression and deterioration.Metformin,a traditional hypoglycemic drug,has recently been discovered to have multiple functions including antitumor effects.There have been studies on the mechanism of metformin for the treatment of pituitary tumors,but it is uncertain whether it will provide new adjuvant or alternative therapies for the treatment of these tumors.We analyzed the potential mechanisms of action of metformin with respect to the inhibition of pituitary tumor growth and hormone secretion by reviewing the available literature.

Clinical and Biochemical Characteristics of Growth Hormone-Secreting Pituitary Tumors

To investigate the difference of biochemical characteristics on gsp positive and gsp negative growth hormone (GH) secreting pituitary tumors, 18 GH secreting pituitary tumors were examined for their clinical characteristics and gsp oncogenes. All patients received the pituitary function combinative stimulating test. It was found that there were no difference in the sex, age, tumor size, course of disease and plasma basal GH levels with gsp positive and gsp negative patients. The plasma levels of PRL were increased in most patients (11/18), and the plasma levels of TSH in gsp positive patients were higher than those in gsp negative patients ( P <0.05). There was no significant difference in the responses to pituitary combinative stimulating test in gsp positive and gsp negative patients. It was concluded that there was little difference in the clinical biochemical characteristics of gsp positive with gsp negative GH secreting pituitary tumors.

EXPRESSION OF EPIDERMAL GROWTH FACTOR, TRANSFORMINGGROWTH FACTOR-α AND THEIR RECEPTOR IN HUMAN PITUITARY TUMORS

Objective: To explore the role of growth factor autocrine stimulation in the pathogenesis of human pituitary tumors. Methods: The expression of EGF, TGF-( and EGFR were studied by immunohisto-chemical method on paraffin-embedded sections of 30 cases pituitary tumor. Results: EGFR and its ligands EGF, TGF-( expressed in majority of pituitary tumors. The expression of EGFR and its ligands varied with cells' intensity, density and type. Conclusion: The EGF autocrine stimulating exerted in the pituitary tumor development process, that tyrosine kinases inhibitors may be useful for pituitary tumors treatment.

A systematic survey of LU domain-containing proteins reveals a novel human gene,LY6A,which encodes the candidate ortholog of mouse Ly-6A/Sca-1 and is aberrantly expressed in pituitary tumors

The Ly-6 and uPAR(LU)domain-containing proteins represent a large family of cell-surface markers.In particular,mouse Ly-6A/Sca-1 is a widely used marker for various stem cells;however,its human ortholog is missing.In this study,based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins,we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1.This gene,hereby named LY6A,reversely overlaps with a lncRNA gene in the majority of exonic sequences.We found that LY6A is aberrantly expressed in pituitary tumors,but not in normal pituitary tissues,and may contribute to tumorigenesis.Similar to mouse Ly-6A/Sca-1,human LY6A is also upregulated by interferon,suggesting a conserved transcriptional regulatory mechanism between humans and mice.We cloned the full-length LY6A cDNA,whose encoded protein sequence,domain architecture,and exon‒intron structures are all well conserved with mouse Ly-6A/Sca-1.Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane.Collectively,these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.

Clinical application of reserved gastric tube in neuroendoscopic endonasal surgery for pituitary tumor

BACKGROUND The neuroendoscopic approach has the advantages of a clear operative field,convenient tumor removal,and less damage,and is the development direction of modern neurosurgery.At present,transnasal surgery for sphenoidal pituitary tumor is widely used.But it has been found in clinical practice that some patients with this type of surgery may experience post-operative nausea and vomiting and other discomforts.AIM To explore the effect of reserved gastric tube application in the neuroendoscopic endonasal resection of pituitary tumors.METHODS A total of 60 patients who underwent pituitary adenoma resection via the endoscopic endonasal approach were selected and randomly divided into the experimental and control groups,with 30 in each group.Experimental group:After anesthesia,a gastric tube was placed through the mouth under direct vision using a visual laryngoscope,and the fluid accumulated in the oropharynx was suctioned intermittently with low negative pressure throughout the whole process after nasal disinfection,during the operation,and when the patient recovered from anesthesia.Control group:Given the routine intraoperative care,no gastric tube was left.The number of cases of nausea/vomiting/aspiration within 24 h post-operation was counted and compared between the two groups;the scores of pharyngalgia after waking up,6 h post-operation,and 24 h postoperation.The frequency of postoperative cerebrospinal fluid leakage and intracranial infection were compared.The hospitalization days of the two groups were statistically compared.RESULTS The times of postoperative nausea and vomiting in the experimental group were lower than that in the control group,and the difference in the incidence of nausea was statistically significant(P<0.05).After the patient woke up,the scores of sore throat 6 h after the operation and 24 h after operation were lower than those in the control group,and the difference was statistically significant(P<0.05).The number of cases of postoperative cerebrospinal fluid leakage and intracranial infection was higher than that of the control group,but there was no statistically significant difference from the control group(P>0.05).The hospitalization days of the experimental group was lower than that of the control group,and the difference was statistically significant(P<0.05).CONCLUSION Reserving a gastric tube in the endoscopic endonasal resection of pituitary tumors,combined with intraoperative and postoperative gastrointestinal decompression,can effectively reduce the incidence of nausea,reduce the number of vomiting and aspiration in patients,and reduce the complications of sore throat The incidence rate shortened the hospitalization days of the patients.

Secondary diabetes due to different etiologies:A problem worthy of attention

There are many factors in the occurrence of diabetes,which can result in insufficient insulin secretion and insulin receptor resistance.Including pituitary tumors,can also lead to the occurrence of diabetes,if the primary disease can not be well controlled in time,such secondary diabetes control is more difficult.In the process of clinical diagnosis and treatment,these factors need to be taken into account,timely detection and treatment of primary diseases,so as to reduce the possibility of clinical missed diagnosis.

The Clinical Effect Two Approaches of Microsurgery the Treatment for Pituitary Tumor

Objective:To analyze the effect of two approaches of microsurgery in the treatment of pituitary tumor.Methods:The main body of this study was 69 patients with pituitary tumor who came to the hospital between December 2016 and December 2019.Taking the coin method as the standard,group A underwent nasal-sphenoid sinus approach with 36 cases;group B underwent transcranial approach with 33 cases.The treatment effects were compared.Results:The total effective rate of group A was 94.44%,and that of group B was 72.73%;the therapeutic index of group A was better than that of group B;the complication rate of group A was 8.33%,and that of group B was 30.30%(P<0.05).After treatment,the tumor volume of both groups decreased,and group A was smaller than group B(P<0.05).Conclusion:Nasal-sphenoid sinus approach for patients with pituitary tumors can improve the treatment index,enhance the curative effect,reduce the size of the tumor,and have better safety.

Effect of insulin-like growth factor-1 on pituitary tumor transforming gene in glioma C6 cells

Objective: To investigate the effect of insulin-like growth factor-1 (IGF-1) on pituitary tumor transforming gene (PTTG) in glioma C6 cells. Methods: Glioma C6 cells were divided into four groups: A group, treated without IGF-1; B group, treated with 0.1 ng/mL dose of IGF-1; C group, treated with 1 ng/mL dose of IGF-1; D group, treated with 10 ng/mL dose of IGF-1. PTTG mRNA was detected by reverse transcription polymerase chain reaction (RT-PCR), western blotting was used to detect the expression of PTTG protein. Results: The expressions of PTTG mRNA were 1.370 ± 0.212, 2.198 ± 0.354, 3.452 ± 0.332, and 4.576 ± 0.387 respectively in the four groups, and there was a significantly difference between any two groups (P < 0.01). The protein expressions of PTTG in the four groups were 1.407 ± 0.334, 1.813 ± 0.465, 2.412 ± 0.576, and 3.128 ± 0.665 respectively, and there was a significantly difference between any two groups (P < 0.01). Conclusion: IGF-1 can up-regulate the expression of PTTG significantly in dosage-dependent manner.

Bisecreting Pituitary Neuroendocrine Tumors: About 9 Cases at the Abass Ndao Hospital Center in Dakar

Introduction: Pituitary neuroendocrine tumor (PitNET) may present multisecreting forms. Identifying its forms helps to guide management. This management is a real challenge, given the limited resources in our regions. In view of advances in the management of these multisecreting pituitary neuroendocrine tumors and the lack of published data in Africa, and in Senegal particularly, this survey was carried out with the aim of describing the epidemiological, clinical and therapeutic aspects of multisecreting PitNETs. Patients and Method: It was a multicenter, retrospective, descriptive and analytical study carried out on files collected from 1st January 2008 to 31 December 2022 in the neurosurgery departments of the Fann and Principal hospitals in Dakar and the endocrinology department of the Abass Ndao hospital in Dakar. Results: Of the 242 patients treated for PitNET, 09 presented (the mean age of our patients was 41.7 ± 11 years) with bihormonal PitNET, i.e. a proportion of 3.71%. Two types of association were found: 08 tumors with GH (Growth Hormon) + PRL (prolactin) secretion and 01 PitNET with ACTH (Adreno Corticotropic Homon) + prolactin secretion. Clinically, gonadotropic insufficiency was found in all patients (100%). Dysmorphic syndrome was found in 6 patients (66.7%) and tumor syndrome in 7 patients (77.8%). Ophthalmological evaluation revealed a decrease in visual acuity in 66.6% of patients. All had macroadenomas, with extension noted in 02 patients. All patients underwent transsphenoidal surgery with complications such as transient diabetes insipidus (3 patients, 33.3%), followed by cerebrospinal fluid leaks (1 patient, 11.1%). Remission was noted in all 5 patients tested. A comparison between the different secretory forms did not reveal any significant difference in the frequency of postoperative complications. Conclusion: Despite the lack of immunohistochemistry, two types of association were found: ACTH-PRL and GH-PRL. All were macroadenomas, the majority with an associated tumor syndrome. The latter was significantly less frequent in bisecreting PitNETs compared with monosecreting and non-functional forms. However, there was no significant difference in the occurrence of post-operative complications between the three secretory forms of PitNETs.

Submental tracheal intubation for resection of recurrent giant pituitary tumor:a case report

Airway management in the patients who receive transmaxillary approach for resection of giant pituitary tumor presents a clinical challenge to the anesthesiologists. Oral or nasal route for tracheal intubation can interfere with surgical procedures. This report describes submental tracheal intubation for airway management in a patient who underwent resection of recurrent giant pituitary tumor via transmaxillary approach. Submental tracheal intubation is an adaptable and safe alternative technology for airway management during operation.

Application and Care of Two Kinds of Sphenoid Sinus Packing Materials after Pituitary Tumor Resection with the Transnasal Endoscopic Approach

Background: Neuroendoscopic transsphenoidal approach for resection of pituitary adenomas has the advantages of less damage, fewer complications, and a faster recovery than the traditional approach and has beening favored by neurosurgeons. However, there has no standard method of selecting suitable packing materials after the operation to relieve pain in patients and achieve the ideal hemostatic effect. We compared the postoperative complications and treatment effects of two different packing materials in patients with pituitary adenomas. Objective: To investigate the advantages and disadvantages of using a catheter balloon and iodoform gauze for hemostasis in patients undergoing pituitary tumor resection by neuroendoscopic transsphenoidal approach. Materials and Methods: We retrospectively analyzed these data of 48 cases treated with pituitary adenoma resection by the single nasal approach from January 2018 to October 2019 in Sun Yat-sen University Cancer Center. According to the type of sphenoid sinus packing material used, these patients were divided into balloon tamponade oppression group (24 cases) and tela iodoformum oppression group (24 cases), respectively. The balloon tamponade oppression group received catheter balloon tamponade oppression hemostasis, and the tela iodoformum oppression group underwent tela iodoformum oppression hemostasis. The outcomes and complications were compared between the two groups in which two kinds of sphenoid sinus packing materials were used for hemostasis after tumor resection by transnasal endoscopic approach. For the catheter balloon compression hemostasis method, on account of the plasticity of the balloon, the volume of water in the balloon can be adjusted according to the size of the patient’s own sphenoid cavity. The amount of bleeding and several complications in terms of discomfort during placement and removal of the packing material, rebleeding after removal of the packing, cerebrospinal fluid rhinorrhea and electrolyte disturbance are compared between the two groups. Results: 48 patients were enrolled. The two groups’ data of patients were similar in age structure, sex ratio, tumor size at baseline and so on. No complications, such as abscess formation, were found in both groups. The success rate in the compression with catheter balloon group was 100% (24 of 24 patients);and in the iodoform gauze group 83.33% (20 of 24 patients). A catheter balloon was more successful in stopping bleeding at early stage than iodoform gauze. There were no statistically significant differences in the hospitalization stay time, operating day to discharge day and tampon indwelling time (P > 0.05). There were also no significant differences in pairwise comparison between the catheter balloon group and iodoform gauze groups in the incidence of cerebrospinal fluid rhinorrhea or electrolyte disturbance between the two groups (P > 0.05). The incidence of headache in the catheter balloon group was statistically significantly lower than that in the iodoform gauze group (P < 0.05). Conclusion: In patients undergoing endoscopic pituitary tumor resection, compression and hemostasis by means of catheterization expansion lead to lower rates of injury and complications and have a good effect, so this method is worthy of being recommended for clinical practice.

ENDOSCOPY ASSISTED TRANSSPHENOIDAL PITUITARY SURGERY

Objective To discuss the surgical procedures and its advantages and disadvantages.Methods Theunilateral trans-septal endonasal approach was employed. Zero degree neuroendoscope was used for nasal mucosal dissection and exploration of anterior wall of sphenoid sinus. The sphenoidotomy was done with the anatomic landmark of inferior margin of middle turbinate and ostia . After the identification of internal carotid artery and optic nerve, the pituitary fossa was opened. Then cut the dura , the margin between adenoma and normal tissue was very clear under endoscope. tumor can be removed safely. There were two patients with suprasellar extension, 30-degree endoscope was used and excellent visualization and tumor removal were obtained. Results No severe complication occurred. Conclusion Endoscopic assisted transsphenoidal pituitary surgery is practical because the operation is done under excellent illumination and visualization.

Clinical case discussions-Hypopituitarism and pituitary apoplexy caused by pituitary Adenomas

A case of“Hypopituitarism and pituitary apoplex induced by pituitary Adenomas”was collected in the Third Affiliated Hospital of Inner Mongolia medical University Geriatric Department.A rare and atypical disease as it is,delayed diagnosis and treatment is easily seen among those cases.Therefore,the paper aims to investigate the difference of clinical characteristics and treatment outcome of pituitary adenomas in elder patient through the case analysis.Clinically,patients with pituitary dysfunction may have life-threatening crisis so that timely diagnosis and aggressive treatment can be effective in reducing the pituitary crisis and reducing the misdiagnosis rate.

Transsphenoidal pituitary surgery with one endonasal incision and modified repairation of sella floor

Objective To study the advantage of modified methods involving incision,repairation of the sella floor etc.in transsphenoidal approach for pituitury tumor removal.Methods The transsphenoidal approach with one endonasal incision of mucosa was performed for resecting pituitary tumor in 86 patients,of which total resection of the tumor in 67 cases and subtotal in 19 cases.Results There was no case with postoperative meningitis and rhinoseptal perforation.Tachocombs were used for repairation of the tumor resection cavection cavity and the sella floor,of which there was no case with postoperative CSF leakage happened.Conclusion These modified methods simplified operative procedurej Areduced damage and prevented postoperative complications of CSF leakage and rhinoseptal perforation etc.

Expressions and their significance of PTTG and PC proteins in glioma

Objective： To investigate the expressions and their relationship of pituitary tumor transforming gene （PTTG） and proliferating cell nuclear antigen （PCNA） in glioma. Methods： The protein expressions of PTTG and PCNA were detected by immunostaining assay using streptavidin-peroxidase （SP） method in 80 cases of glioma. Results： The positive rates of PTTG in grades Ⅰ-Ⅳ gliomas were 56.3%, 68.2%, 80.8%, and 100.0% respectively, and the protein expression of PTTG increased with the increasing of the pathological grade （X^2= 9.602, P 〈 0.05）; The positive rates of PCNA protein were 37.5%, 54.5%, 69.2%, and 93.8% respectively, and the protein expression of PCNA increased with the increasing of the pathological grade （X2 = 12.147, P 〈 0.01）. The expression of PTTG had positive correlation with the expression of PCNA protein （~s = 0.557, P 〈 0.01）. Conclusion： The expressions of PTTG and PCNA proteins were related to malignant degree of glioma, and may cooperate with each other in the tumorigenesis and progression and can be considered as the indicators of the biological behaviors in glioma.

Clinical features,radiological profiles,pathological features and surgical outcomes of pituicytomas:a report of 11 cases and a pooled analysis of individual patient data

Background:Pituicytoma is an extremely rare low-grade glial tumor that is closely related to the neurohypophysis axis.Most studies of pituicytomas include only several cases.To better understand this disease,we reviewed a series of cases of pituicytomas.The diagnosis and treatment of pituicytoma must be further elucidated.Methods:Eleven patients with pituicytoma admitted to Beijing Tiantan Hospital from 2012 to 2019 were selected.The clinical features,including radiological and histological examination,surgical records and prognosis were reviewed.Sixty-eight other previously published cases of pituicytoma also were used to analyze the predictive factors for the results.The Cox regression model was used for univariate and multivariate analyses.Results:Our patients included 5 males(45.5%)and 6 females(54.5%),with a mean age of 49.3 years.The tumor was located in the suprasellar region in 5 patients(45.5%),intrasellar region in 4 patients(36.4%),and intrasellarsuprasellar region in 2 patients(18.2%).All patients were misdiagnosed with other common tumors in the sellar region before the operation.During the operation,gross total resection(GTR)of the tumor was achieved in 6 patients(54.5%),and subtotal resection(STR)was achieved in 5 patients(45.5%).The mean progression-free survival(PFS)time was 29.82 months.Tumor progression after surgical resection occurred in 4 patients(36.4%).Among them,60.0%of the patients(cases 4,5,7)with STR experienced progression,while 16.7%of the patients(case 2)with GTR experienced progression.Combined with the 68 cases in the literature,GTR was an independent risk factor for PFS time(P<0.05).Conclusions:Pituicytomas are more common in middle-aged people and the sellar region.The clinical manifestations of pituicytomas are different,but no diagnostic clinical features have been identified other than an abnormally abundant blood supply.Currently,GTR is the best approach for the treatment of pituicytomas.More patients and longer follow-up periods were needed to further elucidate the biological features of pituicytomas.

Induction of Rat Prolactinoma by β－Estradiol and Its Relation to Expression of c－myc Oncogene

Sprague-Dawley rats were implanted with silastic capsules containing β-estradiol. After 60 days, their pituitary weights, serum prolactin contentsand transcription level of c-myc proto-oncogene were found increasedsignificantly. It was also found that the anterior pituitary cells proliferatedsignificantly, but their differentiation was suppressed.

Predictive value of pituitary tumor morphology on outcomes and complications in endoscopic transsphenoidal surgery

Purpose:Endoscopic transsphenoidal surgery(ETSS)is an increasingly utilized approach for resection of pituitary tumors.Prior studies have evaluated preoperative tumor size,location,and extent as prognostic factors for surgical resection.There is little data on the relationship between preoperative pituitary tumor radiographic morphology and surgical outcomes.Study Design:Retrospective longitudinal study.Setting:Single tertiary care institution.Subjects and Methods:Preoperative magnetic resonance imaging and computed tomography scans from patients undergoing ETSS for pituitary tumor resections from 2007 to 2017 were retrospectively evaluated.A neuroradiologist classified these pituitary tumors into six morphologic groups,each defined by volume,dimensions,extension,and shape.Surgical difficulty,rates of incomplete resection,and postoperative complications were then stratified in relation to the morphologic groups.Results:Pituitary tumors from 131 patients were classified from preoperative imaging into six characteristic morphologies:(1)microtumor,(2)round,(3)transverse oblong,(4)superior-inferior oblong,(5)bilobed,and(6)large lobulated.Tumors that were characterized with the large lobulated,bilobed,and transverse oblong morphologies correlated with higher rates of postoperative evidence of residual tumor(70%,36%,and 47%,respectively,all P<0.002).Likewise,large lobulated,bilobed,and transverse oblong morphologies were also associated with intraoperative cerebrospinal fluid leaks(70%,31%,and 35%,respectively,all P<0.05).Conclusions:We describe a novel descriptive system for the morphology of pituitary tumors that can be determined from preoperative imaging.Different tumor morphologic groups are associated with varying degrees of gross tumor resection,complications,and surgical difficulty.Utilizing pituitary tumor morphology may aid surgeons in planning the extent of resection,need for complex closure,and patient counseling.

Prospective study of transsphenoidal pituitary surgery： is tumor volume a predictor for the residual tumor？

Background The presence of residual tumor after surgery for pituitary adenoma may necessitate further treatment. The suprasellar and parasellar extension of the tumor have been widely considered as the predictors for residual tumor. However there is scarcity of studies regarding the preoperative tumor volume and residual tumor. This study was conducted to evaluate if tumor volume could predict the outcome of transsphenoidal pituitary surgery. Methods A prospective study was designed and 48 patients who underwent transsphenoidal pituitary surgery within 1 year in the First Affiliated Hospital of Xi＇an Jiaotong University were included in this study. The preoperative tumor volume and immediate postoperative tumor volume （within 4-7 days） were calculated in the contrast magnetic resonance imaging by using the formula of ellipsoid. All these volumes were divided into three subgroups, i.e. group 1, group 2 and group 3 with preoperative volume of less than 4 cm3, 4-8 cm3, and more than 8 cm3 respectively. The parasellar and suprasellar extension of the tumor were also classified by Knosp and modified Hardy＇s classifications. Results Baseline characteristics were comparable. The preoperative tumor volume of more than 8 cm3 （group 3, （12.1±1.1） cm3） had increased risk on postoperative tumor residue （P 〈0.01） than the other two groups （（2.1±0.3） cm3 and （6.1±0.3） cm3 in groups 1 and 2）. The mean postoperative volume in group 3 patients （（2.2±0.1） cm3） was significantly higher than the other two groups （P 〈0.01）. Conclusion Preoperative volume of more than 8 cm3 can be considered as a predictor for postoperative residual volume.

Carotid artery injury in endoscopic endonasal surgery: Risk factors, prevention, and management

Objective:Endoscopic approaches for sinus and skull base surgery are increasing in popularity.The objective of this narrative review is to characterize risk factors for internal carotid artery injury in endoscopic endonasal surgery(EES),highlight preventative measures,and illustrate key management principles.Data Sources:Comprehensive literature review.Methods:Relevant literature was reviewed using PubMed/MEDLINE.Results:Carotid artery injury in EES is rare,with most studies reporting an incidence below 0.1%.Anatomic aberrancies,wide dissection margins,as well as specific provider and hospital factors,may increase the risk of injury.Multidisciplinary teams,comprehensive preoperative imaging,patient risk assessment,and formal training in vascular emergencies may reduce the risk.Management protocols should emphasize proper visualization of the injury site,fluid replacement,rapid packing,angiography,and endovascular techniques to achieve hemostasis.Conclusions:While EES is a relatively safe procedure,carotid artery injury is a devastating complication that warrants full consideration in surgical planning.Important preventative measures include identifying patients with notable risk factors and obtaining preoperative imaging.Multidisciplinary teams and management protocols are ultimately necessary to reduce morbidity and mortality.