Genotype-phenotype landscape of pituitary adrenocorticotroph hormone adenoma / 中华内分泌代谢杂志

Objective:Cushing′s disease(CD) is caused by the pituitary adrenocorticotroph hormone(ACTH) secreting adenomas, leading to increased serum cortisol levels and various abnormal metabolic processes. Untreated CD is linked to high mortality, thus it is critical to elucidate its pathogenesis. This study aims to explore the pathogenesis of pituitary ACTH adenomas using whole-genome sequencing analysis.Methods:Fresh tumor tissues and peripheral blood samples were collected in 9 confirmed cases of pituitary ACTH adenomas who underwent surgery. Whole genome sequencing was then performed, followed by analysis and verification of single nucleotide mutations, copy number variation(CNV) and chromosome structure variations.Results:Somatic USP8 mutations(p.Ser718del, p. Ser718Pro, p. Pro720Arg, p. Pro720Gln) were found in 5 patients, with a rate of 55.6%; CNV of USP8 was detected in 1 patient; TP53(p.Cys135Tyr), NF1(p.Val1049Glufs*11) and KMT2C(c.3323+ 1G>A) mutations were identified in 1 patient harboring wild-type USP8. CNV analysis showed a loss of heterozygosity in multiple chromosomes in a wild-type USP8 patient. Structural variations were found in 2 with unknown significance. No germline gene mutations were detected in this study.Conclusion:Somatic USP8 mutations, increased copy number of USP8, variations of tumor-related genes such as TP53 and extensive somatic CNV all contribute to pathogenesis of CD. Chromosomal structure variations may suggest high-risk pituitary ACTH adenomas, and call for frequent follow-up and aggressive treatment.

Clinical and pathological features of 166 patients with nonfunctioning pituitary adenomas / 中华内分泌代谢杂志

Objective:To investigate the clinical features and pathological classification of patients with nonfunctional pituitary adenomas(NFPAs)in single medical center according to 2017 World Health Organization.Methods:The clinical and pathological characteristics of 166 patients with NFPAs diagnosed by neurosurgery in Peking Union Medical College Hospital from April 2019 to January 2020 were analyzed retrospectively.Results:In 166 patients, the ratio of male to female was almost equal(1.05∶1). Their average operation age was(49.9±12.3) years, which was significantly higher than that of functional pituitary tumor patients in the same period. Headache, visual acuity decline, and visual field defect were the most common causes for the first visit. All the maximum diameter of tumors was more than 10 mm, and 15 cases(9.0%)were giant tumors. 18 patients(10.8%)were recurrent cases. According to the results of immunohistochemistry for anterior pituitary hormones and transcriptional factors, the most common pathological type was gonadotroph adenomas(50.6%), followed by corticotroph adenomas(24.7%), plurihormonal pituitary adenomas(11.4%), PIT-1-positive adenomas(6.6%), and null cell adenomas(6.6%). Gonadotroph adenomas were more common in men(male∶female ratio=4.1∶1), while corticotroph adenomas occurred mainly in women(male∶female ratio=1∶12.7). The average age of patients with gonadotroph adenomas was the highest, while those of patients with PIT1-positive adenomas and rare combining IHC plurihormonal pituitary adenoma were significantly lower than that of the former. There were no significant differences in the mean diameters of tumors, the proportion of giant adenomas, and recurrent cases among different pathological types of tumors. However, the mean Ki-67 index of PIT-1-positive adenomas was significantly higher than those of other groups( P=0.001). Conclusion:Although the clinical manifestations of NFPAs were similar, their pathological classifications were different. Gonadotroph adenomas occurs mainly in male patients while corticotroph adenomas is more common in women. The prognosis may be different among various pathological types of NFPAs.

Research progress of medical image post-processing techniques based on computer in localization of epileptogenic zone in epilepsy patients / 中国介入影像与治疗学

About 30%-40% of patients with epilepsy remain medically intractable and may be considered as candidates for surgical treatment. Precise localization of the epileptogenic zone (EZ) through comprehensive presurgical evaluations is crucial for achieving good outcome. However, currently the interpretation of neuroimaging relies immensely on clinicians' experience, which is subjective and time-consuming. In order to improve the accuracy of EZ localization, medical image post-processing techniques have been applied. The results indicated that post-processing techniques have the advantages of identifying subtle abnormalities in brain structure and function objectively and precisely, thus may provide an accurate and effective solution for EZ localization. The advancements of existing medical image post-processing methods used in EZ localization were reviewed in this article.

Influence of Nasal Disinfection on Nasal Bacterial Colonization through the Transsphenoidal Approach / 中国医学科学院学报

Objective To explore the influence of the iodine disinfection on nasal bacterial colonization through the transsphenoidal approach. Methods Totally 133 pituitary adenoma patients who underwent transsphenoidal surgery in our department from January to August 2017 were enrolled in this study. Before disinfection,pharyngeal swabs of inferior turbinate root secretions were taken for bacterial culture. After iodine disinfection,pharyngeal swabs were taken again at the same site. Changes in the nasal bacterial spectrum before and after disinfection were compared. Patients were followed up for three months after the surgery,during which any intracranial infection/bacteraemia was recorded,and its correlation with nasal bacteria colonization was analyzed. Results Nasal bacterial colonization was detected in 45 (33.8%) of 133 patients before iodine disinfection and in only 6 cases (4.5%) after iodine disinfection (χ=34.5,P=0.000). Thus,iodine disinfection eliminated 86.7%(39/45) of the colonized bacteria. The most common nasal bacterium was Staphylococcus aureus (24.4%,11/45),followed by Klebsiella pneumoniae (24.4%,11/45),and Staphylococcus epidermidis (13.3%,6/45). One patient had high fever and chills 2 days after surgery,but blood culture and cerebrospinal fluid culture showed negative Results . After the administration of third-generation cephalosporins,the symptoms disappeared after two days. Conclusion sThere are colonized bacteria in nasal cavity. Iodine disinfection of nasal cavity can effectively clear most of the nasal bacteria. The possibility of intracranial infection/bacteremia after transsphenoidal approach is low.

Effects of dexmedetomidine on the emergence of patients undergoing transnasal transsphenoidal pituitary tumor resection / 临床麻醉学杂志

Objective To evaluate the effect of dexmedetomidine on the tolerance to endotracheal tube, on agitation and other complications of patients undergoing transnasal transsphenoidal pituitary tumor resection.Methods One hundred and twenty-four patients aged 18-65 years, ASA physical status Ⅰ or Ⅱ) were randomly assigned to dexmedetomidine group (group D, n=60) and control group (group C, n=62).Group D were given intravenous infusion of dexmedetomidine during the operation and group C with saline.The extubation time, observation time in the post-anesthesia care unit (PACU), the incidence of emergence agitation, cough, postoperative sore throat and hoarseness were analyzed.Results The extubation time [(29.7±11.5) min vs (22.2±8.5) min] and the length of stay in PACU [(41.5±11.8) min vs (35.3±10.0) min] were significantly longer in group D than those in group C (P<0.05).There was no significant difference of the incidence of emergence agitation (26.3% vs 32.3%), cough (49.1% vs 53.2%), postoperative sore throat (14.0% vs 24.2%) and hoarseness (10.5% vs 19.4%) between two groups.Conclusion Intraoperative intravenous administration of dexmedetomidine can prolong the extubation time and the length of stay in PACU.The incidence of agitation, cough, postoperative sore throat and hoarseness was not affected by dexmedetomidine.

Correlation between Different Postoperative Serum Cortisol Cut-off Values Measured in Different Periods and Long-term Outcomes in Patients with Cushing's Disease / 中国医学科学院学报

Objective To investigate the correlation between different postoperative serum cortisol cut-off values measured in different periods and the long-term outcomes in patients with Cushing's disease (CD). Methods The clinical data of 102 CD patients undergoing transsphenoidal surgery (TSS) in Peking Union Medical College Hospital from May 1985 to July 2008 were analyzed retrospectively. The differences of long-term outcomes were compared between patients with cortisol levels below 2 μg/dl (2 μg/dl group) and levels between 2 and 5 μg/dl (5 μg/dl group) in the 1postoperative day and 3 and 6 months after surgery. Results The mean follow-up duration was (10.7±1.7) years (range:5-29.1 years). Among these 102 patients,the disease was cured in 74 patients (72.5%) and recurred in 28 patients (27.5%). On the 1postoperative day,there were 63 patients in the 2 μg/dl group,in which 48 patients (76.2%) achieved long-term cure;there were 39 patients in the 5 μg/dl group,in which 26 (66.7%) achieved long-term cure. The difference was not statistically significant (χ=1.097,P=0.295). Three months after TSS,the long-term cure rate was 84.2% (48/57) in the 2 μg/dl group,which was significantly higher than that (65.0%,26/40) in the 5 μg/dl group (χ=4.795,P=0.029). Six months after TSS,the long-term cure rate was 88.7% (47/53) in the 2 μg/dl group,which was significantly higher than that(69.2%,27/39) in the 5 μg/dl group(χ=5.400,P=0.020). Conclusion The serum cortisol level of below 2 μg/dl is more useful than 2-5 μg/dl 3 months and 6 months after surgery in predicting the prognosis of CD patients.

Ethical Issues in the Signature and Execution of Certificate of Authorization of Cancer Patients / 中国医学伦理学

There were some ethical problems in the implementation of certificate of authorization of cancer pa -tients, such as doctors dominate the signing process and show no respect for patients ′rights and interests .It pro-posed to improve rules and regulations , increase transparency , to setup informed consent platform define and verifi-cation, emphasize the licensee to perform the duty of communication , strengthen the construction of the medical staff ethics , in order to safeguard the rights and interests of patients , promote the rational and effective use of medi-cal resources .

Treatment of pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effectiveness of treating giant pituitary adenomas invading cavernous sinus with neuroendoscopy assisted by multiple techniques.</p><p><b>METHODS</b>A total of 72 patients who underwent neuroendoscopic surgery and 55 patients who underwent microscopic surgery for giant pituitary adenomas were enrolled in this retrospective analysis. Both groups received expanded endoscopic endonasal transsphenoidal approach, intraoperative application of navigation, and Doppler.The clinical data of two groups were compared.</p><p><b>RESULTS</b>The two groups were significantly different in total tumor removal rate, operation time, postoperative nasal patency, and postoperative recurrence rate (P=0.004, P=0.0003, P=0.000, and P=0.002, respectively), whereas the cerebrospinal fluid leakage, postoperative diabetes insipidus, and cranial nerve injury were not significantly different (P > 0.05).</p><p><b>CONCLUSIONS</b>Expanded neuroendoscopic endonasal transsphenoidal approach assisted by multiple techniques is the preferred surgical method for giant invasive pituitary adenomas invading cavernous sinus.The lateral cavernous sinus approach and the further molecular biology research will bring more options for the treatment of invasive pituitary adenomas.</p>

Neural endoscopic assisted micro-invasive management of Chiari I malformation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In order to make posterior fossa decompression for the management of Chiari I malformation simple and less invasive while using direct visualization, a novel solely endoscopic procedure has been employed for the decompression of Chiari malformation type I. The objective of this study was to present neural endoscopic posterior fossa decompression and atlas laminectomy for Chiari type I patients.</p><p><b>METHODS</b>Twenty-one patients with Chiari type I underwent neural endoscopic posterior fossa decompression and atlas laminectomy. We described the procedure for neural endoscopic posterior fossa decompression and atlas laminectomy. All patients in this series demonstrated cerebellar tonsil herniation below the foramen magnum in addition to syringomyelia. All patients in the reviewed study underwent preoperative MRI as well as 3-month postoperative MRI. Additional follow-up MRI varied but was usually repeated 12 months to 18 months after surgery. Postoperative MRI studies were retrospectively reviewed and compared with preoperative studies.</p><p><b>RESULTS</b>All patients showed clinical improvements, and none had any complications. Patients with syringomyelia had symptoms entirely disappear. Eleven patients (52.4%) experienced radiographic improvement in syringomyelia (decreased size or resolution) during the follow-up period. Nine patients (42.8%) demonstrated decreased syrinx size and four (19%) demonstrated resolved syrinx. Of the 15 patients with symptomatic syringomyelia, 11 (73.3%) experienced symptomatic improvement. The median time to symptom improvement was four months after surgery. Post surgical MRI examinations indicated complete and sufficient decompression of foramen magnum region.</p><p><b>CONCLUSIONS</b>Endoscope atlanto-occipital decompression surgery is an innovative, safe and effective surgical procedure. It has similar results compared to traditional surgery, however with the added advantages of being minimal invasive, having fewer complications, decreased influence on stability of occipital bony structure, and a faster recovery as well as reduced hospital stay and expenses.</p>

Magnetic resonance imaging characteristics and surgical results of adrenocorticotropin-secreting pituitary adenomas / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate magnetic resonance imaging (MRI) characteristics and surgical results of adrenocorticotropin (ACTH)-secreting pituitary adenomas.</p><p><b>METHODS</b>MRI characteristics and relationship between MRI positive rate and surgical results of 266 patients with pathologically confirmed 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 MRI scanner, and dynamic enhanced MRI was performed in 39 patients. All patients underwent transsphenoidal adenomectomy. Endocrinological examinations and assessments were performed.</p><p><b>RESULTS</b>Preoperative MRI 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 MRI 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).</p><p><b>CONCLUSIONS</b>Enhanced coronal pituitary MRI is helpful for preoperative localization of ACTH-secreting pituitary microadenoma. Dynamic enhanced MRI may improve detection rate of microadenoma. There is no marked difference in the surgical results for patients with preoperative MRI results indicating presence or absence of microadenoma.</p>