Changing presentation of acromegaly in half a century: a single-center experience.

OBJECTIVE: Investigate the changes in the characteristics of presentation, in patients with acromegaly over a period of approximately half a century. METHODS: The medical records of patients diagnosed with acromegaly between 1980 and 2023 were retrospectively reviewed. The collected data were examined to assess any changes observed over the years and a comparison was made between the characteristics of patients diagnosed in the last decade and those diagnosed in previous years. RESULTS: A total of 570 patients were included in the study, 210 (37%) patients were diagnosed in the last decade. Patients diagnosed before 2014 had longer symptom duration before diagnosis, advanced age, larger pituitary adenomas, higher incidence of cavernous sinus invasion, and higher GH and IGF-1 levels than those diagnosed last decade (p < 0.05, for all). Furthermore, the patients diagnosed before 2014 had a lower rate of surgical remission (p < 0.001), and a higher prevalence of comorbidities such as diabetes, hypertension, colon polyps, and thyroid cancer at the time of diagnosis (p < 0.05, for all). CONCLUSION: There may be a trend for earlier detection of patients with acromegaly.

Machine learning as a clinical decision support tool for patients with acromegaly.

OBJECTIVE: To develop machine learning (ML) models that predict postoperative remission, remission at last visit, and resistance to somatostatin receptor ligands (SRL) in patients with acromegaly and to determine the clinical features associated with the prognosis. METHODS: We studied outcomes using the area under the receiver operating characteristics (AUROC) values, which were reported as the performance metric. To determine the importance of each feature and easy interpretation, Shapley Additive explanations (SHAP) values, which help explain the outputs of ML models, are used. RESULTS: One-hundred fifty-two patients with acromegaly were included in the final analysis. The mean AUROC values resulting from 100 independent replications were 0.728 for postoperative 3 months remission status classification, 0.879 for remission at last visit classification, and 0.753 for SRL resistance status classification. Extreme gradient boosting model demonstrated that preoperative growth hormone (GH) level, age at operation, and preoperative tumor size were the most important predictors for early remission; resistance to SRL and preoperative tumor size represented the most important predictors of remission at last visit, and postoperative 3-month insulin-like growth factor 1 (IGF1) and GH levels (random and nadir) together with the sparsely granulated somatotroph adenoma subtype served as the most important predictors of SRL resistance. CONCLUSIONS: ML models may serve as valuable tools in the prediction of remission and SRL resistance.

Should we take precautions to avoid respiratory compromise while delaying CPAP resumption following transsfenoidal surgery? An alternative approach in a patient with severe obstructive sleep apnea: case report.

BACKGROUND: We describe a patient with severe obstructive sleep apnea scheduled for transsfenoidal surgery. Early postoperative use of continuous positive airway pressure (CPAP) was considered unsafe because increased risk of intracranial complications. METHODS: Aiming to bypass the upper airway obstruction and thus avoid CPAP, a 6-mm nasopharyngeal airway was introduced by the surgical team under endoscopic vision. In the postoperative period and during follow-up, patient and his family did not complain about apnea/hypopnea episodes and nasopharyngeal airway was tolerated comfortably. CONCLUSION: We recommend this technique as an alternative in obstructive sleep apnea patients undergoing transsfenoidal surgery.

The effects of pre-operative somatostatin analogue therapy on treatment cost and remission in acromegaly.

PURPOSE: To investigate the effects of preoperative somatostatin analogue (SSA) treatment on the annual cost of all acromegaly treatment modalities and on remission rates. METHODS: The medical records of 135 patients with acromegaly who were followed at endocrinology clinic of Cerrahpasa Medical Faculty for at least 2 years after surgery between 2009 and 2016 were reviewed. RESULTS: The mean follow-up time was 50.9 ± 25.7 months. Early remission was defined according to 3rd month values in patients who didn't achieve remission, and 6th month values in patients who achieved remission at the 3rd month after surgery. The early and late remission rates of the entire study population were 40% and 80.7%, respectively. The early remission of the preoperative SSA-treated group (61.5%) was significantly higher than SSA-untreated group (31.2%) (p = 0.002). The early remission of the preoperative SSA-treated patients with macroadenomas (52.2%) was also significantly higher than the SSA-untreated group (23.5%) (p = 0.02). In the subgroup analysis; this difference was much more pronounced in invasive macroadenomas (p = 0.002). There were no differences between the groups in terms of late remission.The median annual cost of all acromegaly treatment modalities in study population was €3788.4; the cost for macroadenomas was significantly higher than for microadenomas (€4125.0 vs. €3226.5, respectively; p = 0.03). Preoperative SSA use in both microadenomas and macroadenomas didn't alter the cost of treatment. The increase in the duration of preoperative medical treatment had no effect on early or late remissions (p = 0.09; p = 0.8). CONCLUSIONS: Preoperative medical treatment had no effect on the costs of acromegaly treatment. There was a benefical effect of pre-operative SSA use on early remission in patients with macroadenomas; however, this effect didn't persist long term.

Transsphenoidal surgery for pituitary adenomas in pediatric patients: a multicentric retrospective study.

INTRODUCTION: Pediatric pituitary adenomas are rare lesions. Incidence is reported between 1 and 10% of all childhood brain tumors and between 3 and 6% of all surgically treated adenomas. Although pituitary adenomas present with symptoms of hormone hypersecretion or neurological disruptions secondary to mass effect, they are almost constantly benign. Characteristics of patients may vary in different studies according to age, gender, size of adenoma, hormonal activity, and recurrence rates. METHODS: Data on consecutive pediatric patients who were operated for pituitary adenoma with endoscopic endonasal transsphenoidal surgery (EETS) and transsphenoidal microsurgery (TMS) in the Department of Neurosurgery, Istanbul University Cerrahpasa Medical Faculty, Istanbul, Turkey, in the Neurosurgical Unit of the San Matteo Hospital, Pavia, Italy, and in the Division of Neurological Surgery Department of Biotechnology and Life Sciences, University of Insubria-Varese, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy, between July 1997 and May 2018, were analyzed. Twenty-seven patients (11 males and 16 females), who were 18 years old or younger at the time of surgery, were included in the study. Medical records, images, and operative notes of patients were retrospectively reviewed. RESULTS: There were 16 females (59.3%) and 11 males (40.7%). Mean age was 15.3 ± 3.3 (4-18). Thirty-two surgical procedures were performed for 27 patients (6 children required second operation). Thirteen patients (48.14%) had Cushing's disease (CD), 5 patients (18.5%) had growth hormone (GH)-secreting adenoma, 5 patients (18.5%) had prolactinoma, and 4 patients (14.8%) had non-functional adenoma. Twenty-two patients (81.4%) met remission criteria, and 5 patients (18.5%) did not meet remission criteria. Four patients met remission criteria after the second operation. CONCLUSION: Transsphenoidal approach affords effective release of mass effect and not only restoration but also perpetuation of normal endocrine functions in the majority of pediatric pituitary adenoma patients. Satisfactory results are reported with both EETS and TMS in the literature. Despite the technical difficulties in pediatric age, transsphenoidal resection of adenoma is still the mainstay treatment that provides cure in pediatric patients.

Neurosurgical treatment of Cushing disease in pediatric patients: case series and review of literature.

AIM: Pituitary adenomas are rare in childhood in contrast with adults. Adrenocorticotropic hormone (ACTH)-secreting adenomas account for Cushing's disease (CD) which is the most common form of ACTH-dependent Cushing's syndrome (CS). Treatment strategies are generally based on data of adult CD patients, although some difficulties and differences exist in pediatric patients. The aim of this study is to share our experience of 10 children and adolescents with CD. PATIENTS AND METHOD: Medical records, images, and operative notes of 10 consecutive children and adolescents who underwent transsphenoidal surgery for CD between 1999 and 2014 in Cerrahpasa Faculty of Medicine were retrospectively reviewed. Mean age at operation was 14.8 ± 4.2 years (range 5-18). The mean length of symptoms was 24.2 months. The mean follow-up period was 11 years (range 4 to 19 years). RESULTS: Mean preoperative cortisol level was 23.435 µg/dl (range 8.81-59.8 µg/dl). Mean preoperative ACTH level was 57.358 µg/dl (range 28.9-139.9 µg/dl). MR images localized microadenoma in three patients (30%), macroadenoma in four patients (40%) in our series. Transsphenoidal microsurgery and endoscopic transsphenoidal surgery were performed in 8 and 2 patients respectively. Remission was provided in 8 patients (80%). Five patients (50%) met remission criteria after initial operations. Three patients (30%) underwent additional operations to meet remission criteria. CONCLUSION: Transsphenoidal surgery remains the mainstay therapy for CD in pediatric patients as well as adults. It is an effective treatment option with low rate of complications. Both endoscopic and microscopic approaches provide safe access to sella and satisfactory surgical results.

Germline mutations of aryl hydrocarbon receptor-interacting protein (AIP) gene and somatostatin receptor 1-5 and AIP immunostaining in patients with sporadic acromegaly with poor versus good response to somatostatin analogues.

OBJECTIVE: To determine aryl hydrocarbon interacting protein (AIP) gene variations and AIP and somatostatin receptor (SSTR) 1-5 immunostaining in patients with apparently sporadic acromegaly with poor versus good response to somatostatin analogues (SRLs). METHODS: A total of 94 patients (66 with poor and 28 with good response to SRLs) were screened for the AIP gene variations using Sanger sequencing. Immunostaining was performed in 60 tumors. RESULTS: Several variations, albeit some with undetermined significance, were detected, especially in poor responder patients. The prevalence of AIP mutation was 2.1% in the whole group and 1.5% in patients with poor response to SRLs. AIP, SSTR2A, and SSTR2B immunostainings were decreased in patients with poor response (p < 0.05 for all), and other SSTRs did not differ between the groups (p > 0.05 for all). Patients with low AIP had decreased levels of SSTR2A and SSTR3 (p < 0.05 for all). AIP and SSTR2A immunostainings were positively correlated to the treatment response and age at diagnosis was negatively correlated (p < 0.05 for all). In poor responder patients with high SSTR2A immunostaining, SSTR2B immunostaining and preoperative tumor size were positively and negatively correlated, respectively, to SRL response (p < 0.05 for all). CONCLUSIONS: Lack of response to SRLs does not necessarily increase the risk of harboring AIP mutations. The finding of decreased AIP, SSTR2A, and SSTR2B immunostaining in patients with poor response to SRLs and decreased SSTR2A and SSTR3 level in those with low AIP immunostaining suggests a possible interaction between AIP and some SSTR subtypes that might alter SRL sensitivity.

Endoscopic Endonasal Transethmoidal Approach for the Management of a Traumatic Brain Abscess and Reconstruction of the Accompanying Anterior Skull Base Defect.

Skull base endoscopy in the treatment of brain abscesses has been rarely published. Moreover, endoscopic endonasal transethmoidal approach (EETA) for the treatment of brain abscess following a head trauma has been reported only in a few case reports. We report the management of a patient of intracerebral abscess and reconstruction of the accompanying anterior skull base defect through an EETA.Thirty-year-old male with a frontal lobe abscess due to a penetrating skull base trauma was operated via EETA. After drainage of the abscess, dural and bony defects were repaired to prevent any recurrence. Postoperative radiological imaging revealed prominent decrease in abscess size. The patient did not need any further surgical intervention, and antibiotherapy was adequate.EETA is safe and effective in the management of brain abscesses. Skull base endoscopy provides direct visualization of the abscess cavity through a minimal invasive route, facilitates wide exposure of surrounding neurovascular structures within the operative field, and enables concurrent closure of the skull base defect.

Familial acromegaly due to aryl hydrocarbon receptor-interacting protein (AIP) gene mutation in a Turkish cohort.

Aryl hydrocarbon receptor-interacting protein (AIP) is associated with 15-20% of familial isolated pituitary adenomas and 50-80% of cases with AIP mutation exhibit a somatotropinoma. Herein we report clinical characteristics of a large family where AIP R304X variants have been identified. AIP mutation analysis was performed on a large (n = 52) Turkish family across six generations. Sella MRIs of 30 family members were obtained. Basal pituitary hormone levels were evaluated in 13 family members harboring an AIP mutation. Thirteen of 52 family members (25%) were found to have a heterozygous nonsense germline R304X mutation in the AIP gene. Seven of the 13 mutation carriers (53.8%) had current or previous history of pituitary adenoma. Of these 7 mutation carriers, all but one had somatotropinoma/somatolactotropinoma (85.7% of the pituitary adenomas). Of the 6 acromegaly patients with AIP mutation (F/M: 3/3) the mean age at diagnosis of acromegaly was 32 ± 10.3 years while the mean age of symptom onset was 24.8 ± 9.9 years. Three of the six (50%) acromegaly cases with AIP mutation within the family presented with a macroadenoma and none presented with gigantism. Biochemical disease control was achieved in 66.6% (4/6) of the mutation carriers with acromegaly after a mean follow-up period of 18.6 ± 17.6 years. Common phenotypic characteristics of familial pituitary adenoma or somatotropinoma due to AIP mutation vary between families or even between individuals within a family.

Endoscopic approach to a collision tumor of growth hormone-secreting adenoma and gangliocytoma in the pituitary gland.

The authors share their experience on a collision tumor of growth hormone (GH)-secreting adenoma and gangliocytoma in the pituitary gland, which was reported by few articles in the literature. Also, an intraoperative view of this tumor, operated via endoscopic endonasal transsphenoidal approach, is presented for the first time. A 39-year-old female patient was admitted with clinical manifestation of acromegaly present in a 2-year period. Laboratory investigations revealed high levels of GH and insulinlike growth factor 1. Sellar computed tomography scan and magnetic resonance imaging showed a sellar mass diagnosed as a pituitary adenoma. Based on clinical, biochemical, and radiologic evaluations, GH-secreting pituitary adenoma was diagnosed and operated by endoscopic endonasal transsphenoidal approach achieving total removal of the tumor. Histopathologic examination revealed a collision tumor of GH-secreting adenoma and gangliocytoma. Postoperative radiologic and biochemical investigations showed no residual tumor and total remission. The endoscopic endonasal transsphenoidal approach promotes a close intraoperative view of sellar pathologies. We believe that a detailed histopathologic workup is necessary to diagnose collision tumors, because even a close intraoperative view does not facilitate to differentiate these tumors from a regular pituitary adenoma.

Secondary Pituitary Abscess: A Rare Complication of Transsphenoidal Surgery for Pituitary Adenoma - Description of Two New Cases and Review of the Literature.

Background: Pituitary abscess (PA), a rare complication following transsphenoidal (TS) surgery for pituitary adenoma with an incidence of 0.2%, poses a significant risk; carrying potential morbidity, recurrence, and the necessity for reoperation. Timely suspicion, diagnosis, and treatment are imperative. Patients and Methods: We present two cases and provide a literature review on the symptoms, risk factors, diagnosis, treatment, and outcomes associated with secondary PAs following TS surgery for adenoma. Results: We identified 12 articles reporting a total of 45 cases, in addition to our 2 cases. The primary symptoms were headache and visual impairment, with no fever or specific infectious parameters observed. Predominant risk factors identified included cerebrospinal fluid (CSF) leakage and prior radiotherapy (RT). Our first patient, a 45-year-old male, presented 10 weeks after TS surgery with sudden-onset symptoms, whereas our second patient, a 64-year-old female, presented 22 years postoperatively. In the first case, intraoperative CSF leakage, with the patient's history of allergic rhinitis and frequent nasal irrigation possibly contributed to the development of abscess. In the second case, RT was considered a potential risk factor. Severe headache and subclinical signs of infection associated with a cystic lesion of the pituitary gland were common findings. Both patients underwent endoscopic TS drainage and received appropriate antibiotic therapy, resulting in complete recovery without recurrence. Conclusions: When faced with severe headaches in a patient with a history of TS surgery for a pituitary adenoma, coupled with radiological evidence showing a cystic appearance with peripheral enhancement, taking a proactive approach to promptly identify and intervene in secondary PAs is essential for mitigating potential complications and optimizing patient outcomes.

Caffeine, alcohol, and drug use as work adjuncts among neurosurgeons. Prevalence, contributing factors, and proposed strategies.

BACKGROUND: Neurosurgeons may resort to caffeine, alcohol, and various drugs to maintain peak performance as they grapple with work demands and escalated stress. The prevalence of this controversial strategy remains largely unexplored. METHODS: An anonymous survey of 23 questions formulated by our research group was distributed through personal contacts and neurosurgical societies. Inquiries revolved around the use of medications and other substances for job-related reasons. Data were analyzed via regression and descriptive statistics in python. RESULTS: In total, 215 neurosurgeons (43 residents) were included, with 213 disclosing their gender (94 females). Out of all, 9.3% were <30, 38.1% were 30-39, 44.6% were 40-59 and 7.9% were >60 years old. Most (70.7%) practiced in Europe, 18.6% in Asia, 6.5% in North and South America and the rest in Africa or Australia. While 132 participants stated they consume caffeine to manage challenging schedules, drugs for cognitive and mood enhancement were utilized by 18 and 35 respectively. Alcohol was employed for stress relief by 28 with 4 reporting as heavy drinkers. Drugs posed a solution to sleep disorders for 82, and helped 8 others in strengthening their hand dexterity. Notably, 12 of those claiming drug use, initiated it in medical school. Exercise, self-care activities and relational support were the main alternatives sought. Ultimately, most responders recommended extending mental health assistance and raising awareness about drug use. CONCLUSIONS: Reflecting on our results on job-associated drug use by neurosurgeons, we propose the judicious use of pharmacological or non- adjuncts, alongside the prioritization of neurosurgeons' well-being.

Machine Learning May Be An Alternative To BIPSS In The Differential Diagnosis Of ACTH-Dependent Cushing's Syndrome.

OBJECTIVE: This study aimed to develop machine learning (ML) algorithms for the differential diagnosis of adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) based on biochemical and radiological features. METHODS: Logistic regression algorithms were used for ML, and the area under the receiver operating characteristics curve (AUROC) was used to measure performance. We used Shapley Contributed Comments (SHAP) values, which help explain the results of the ML models to identify the meaning of each feature and facilitate interpretation. RESULTS: A total of 106 patients, 80 with Cushing's disease (CD) and 26 with ectopic ACTH syndrome (EAS), were enrolled in the study. The ML task was created to classify patients with ACTH-dependent CS into CD and EAS. The average AUROC value obtained in the cross-validation of the logistic regression model created for the classification task was 0.850. The diagnostic accuracy of the algorithm was 86%. The SHAP values indicated that the most important determinants for the model were the 2-day 2-mg dexamethasone suppression test, the > 50% suppression in the 8-mg high-dose dexamethasone test, late-night salivary cortisol, and the diameter of the pituitary adenoma. We have also made our algorithm available to all clinicians via a user-friendly interface. CONCLUSION: ML algorithms have the potential to serve as an alternative decision support tool to invasive procedures in the differential diagnosis of ACTH-dependent CS.

European Medical Students' Views on Neurosurgery, with Emphasis on South-East Europe (Albania, Greece, Serbia, and Turkey).

BACKGROUND: Neurosurgery, an intricate and dynamic surgical specialty, faces challenges in attracting medical graduates. Despite its potential appeal, a decreasing trend in medical students opting for surgical specialties, including neurosurgery, is noted. This study aims to assess European medical students' perceptions of neurosurgery, focusing on South-East Europe, and address concerns about the declining interest in this field. METHODS: A comprehensive digital survey, comprising 33 questions, was distributed to 1115 medical students across 17 European countries. The survey, conducted over 9 months, gathered responses through European neurosurgical societies, the European Association of Neurosurgical Societies (EANS), and university channels. Statistical analysis utilized IBM Statistical Package for the Social Sciences, presenting data through counts, proportions, and χ2 tests. RESULTS: The study reveals that, over the survey period, 834 medical students completed the questionnaire, with a predominant representation from South-East Europe. While 43.2% of participants were considering a surgical career, neurosurgery emerged as the most preferred specialty (26.37%). Despite this interest, 80.2% reported insufficient knowledge about pursuing a neurosurgical career, with limited exposure during medical education. Concerns about work-life balance, heavy workload, and hierarchical structures were prominent among respondents. CONCLUSIONS: The findings underscore the need for targeted interventions to address concerns influencing medical students' decisions regarding neurosurgery. Improving neurosurgical education, dispelling misconceptions, and creating a supportive work environment are crucial steps to attract and retain diverse talented individuals in neurosurgery. These efforts will be vital in narrowing the gap between the demand for neurosurgeons and the number of medical graduates entering the field, ensuring a sustainable future for this essential surgical specialty.

Evaluation of depression, quality of life and body image in patients with Cushing's disease.

The aim of this study was to evaluate patients with Cushing's disease (CD) who had undergone transsphenoidal surgery in terms of depression, quality of life (QoL), and perception of body image in comparison to healthy controls. Forty patients with CD and 40 healthy controls matched for demographic characteristics were included in the study. The subjects were evaluated with the Beck depression inventory (BDI), the health survey-short form (SF-36) and the multidimensional body-self relations questionnaire (MBSRQ). Subgroups of the patients with CD were formed on the basis of remission status and BDI scores. In this study, QoL in the general health category and body image were lower in the patients with CD than in the healthy subjects. However, no differences in depression scores were found between the two groups. When the CD group was evaluated according to remission rate, the mean BDI score was significantly higher in the CD patients without remission than in both the CD patients with remission and the healthy subjects (p = 0.04). However, the physical functioning, bodily pain and general health scores of the CD patients without remission on the SF-36 questionnaire were lower than in the CD patients in remission and the healthy subjects (p = 0.002, p = 0.04, p = 0.002, respectively). Fitness evaluation, health evaluation and body areas satisfaction scores of the MBSRQ were significantly different in the three groups (p = 0.003, p = 0.009 and p = 0.001, respectively). In this study, patients with CD were found to have lower QoL, lower body image perception and higher levels of depression compared to healthy controls, particularly if the disease is persistant despite surgery.

Aromatase cytochrome P450 enzyme expression in prolactinomas and its relationship to tumor behavior.

The aim of the study was to evaluate the presence of aromatase cytochrome P450 enzyme (P450AROM) expression in normal pituitary tissues and tumor tissues of patients with prolactinoma and to examine the impact of the P450AROM expression on clinical outcome. Twenty-six consecutive human pituitary tissue samples were obtained from autopsies performed at the Institute of Forensic Medicine. Sixty-four patients who had an adenomectomy between 2000 and 2009 after prolactinoma diagnosis with histologically confirmed pituitary tumor tissues were retrospectively included in this study. The slices from the pituitary tissues were subjected to immunohistochemical staining for evaluation of P450AROM and estrogen receptor beta (ER beta) subunit. Immunohistochemistry results were compared according to age, gender, remission rate, resistance and invasion status of the patients. Higher than normal P450AROM expression was found in the pituitary tissues of the patients with prolactinoma (p < 0.001). P450AROM intensity had no relation to resistance or remission in patients with prolactinoma (p = 0.44, p = 0.45, respectively). The subgroup analysis showed that compared to males without invasive adenoma, males with invasive adenoma had higher P450AROM expression (p = 0.048). ER beta was found to have an impact on resistance (p = 0.049). This study shows that P450AROM expression is present in the pituitary tissues of patients with prolactinoma and that this presence could be important in development and tumor behavior of prolactinomas.

The Combination of Dopamine Agonist Treatment and Surgery May Be the Best Option in Challenging Prolactinoma Cases: A Single-Centre Experience.

OBJECTIVE: To investigate the initial and long-term remission rates, factors related to remission, secondary treatments, and outcomes for patients with prolactinoma who underwent endoscopic transsphenoidal surgery (ETSS). METHODS: The medical files of the 45 prolactinoma patients who underwent ETSS between 2015 and 2022 were retrospectively reviewed. Relevant demographic and clinical data were obtained. RESULTS: Twenty-one (46.7%) patients were female. The median age of patients at ETSS was 35 (interquartile range, 22.5-50) years. The median clinical follow-up of patients was 28 (interquartile range 12-44) months. The initial surgical remission rate was 60%. Recurrence was detected in 7 patients (25.9%). Postoperative dopamine agonists were used in 25 patients, radiosurgery in 2, and second ETSS in 4 patients. After these secondary treatments, the long-term biochemical remission rate was 91.1%. The factors associated with failure in surgical remission are: male gender, older age, higher tumor size, advanced Knosp and Hardy stage, and elevated prolactin level at diagnosis. A prolactin level of <19 ng/mL in the first postoperative week predicted surgical remission with a sensitivity of 77.8% and a specificity of 70.6% in patients who received preoperative dopamine agonist treatment. CONCLUSIONS: In macro adenomas and/or giant adenomas with cavernous sinus invasion, and significant suprasellar extension, which constitutes the difficult part of prolactinoma treatment, neither surgery nor medical treatment alone may be effective enough. Both treatment modalities should be carried out together by a team of neurosurgery and endocrinology in the management of these patients.

Thoracoscopic anatomy and approaches of the anterior thoracic spine: cadaver study.

PURPOSE: [corrected] In spite of the extensive case studies considering thoracoscopic approaches to the anterior thoracic spine, the literature lacks studies of the thoracoscopic anatomic dissection and approaches. In this article, the authors present their study of thoracoscopic anatomy of the anterior spine with illustrated step-wise dissection and approaches for sympathectomy, discectomy and corpectomy. MATERIALS AND METHODS: Four adult cadavers with no history of disease, local trauma or surgery were studied and bilateral thoracoscopic anterior spinal approaches were performed. Thoracoscopic dissections were done in the Department of Anatomy, using Karl Storz 30°, 5 mm and 30 cm rod lens rigid endoscope (Karl Storz and Co., Tuttlingen, Germany). As surgical instrumentation, Karl Storz Rosenthal endoscopic surgical set and 15 mm portals were used for all approaches. RESULTS: For sympathectomy, the cadaver is positioned supine and the port locations are in the third and fifth intercostal spaces in the anterior axillary line. The stellate ganglion is cephalad to the second rib, and the T2 and T3 ganglia are divided just superior to T2 ganglia and inferior to T3. For discectomy, the cadaver is positioned in the lateral decubitus position. The working portal is positioned directly over the affected disc in the posterior axillary line. The camera portal is positioned in the middle axillary line; 2-3 intercostal spaces caudal to the working portal. The rib head is removed and the lateral surface of the pedicle and neural foramen are exposed. The pedicle and the floor of the spinal canal are resected to decompress the ventral aspect of the spinal canal. For corpectomy, the position of the cadaver and ports are as same as for discectomy. The adjacent segmental vessels are divided first, and the discs above and below the targeted corpus are removed. The ipsilateral pedicle is then removed to decompress the anterior spinal cord, followed by median corpectomy. CONCLUSIONS: Thoracoscopic approaches are minimally invasive procedures and they can be used safely in patients who need anterior exposure to the thoracic spine for the treatment of a spectrum of diseases. Knowledge of the normal anatomy and thoracoscopic cadaver dissection are essential steps in improving the learning curve.

Fibroblast Growth Factor Receptor-4 Expression in Pituitary Adenomas is Associated with Aggressive Tumor Features.

PURPOSE: To investigate the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression with radiologic, pathologic, and clinical parameters in pituitary adenomas. METHODS: Among 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we included 161 patients (53 gonadotroph, 26 corticotroph, 25 null cell, 22 lactotroph, 13 somatotroph, 8 adenomas with unusual combination, 7 Pit-1 positive adenomas, and 7 lactosomatotroph) based on availability of pathology specimens. Patients' radiologic, pathologic, and clinical parameters were determined. FGFR-4 immunostaining was evaluated using a semi-quantitative histologic score (H-score). RESULTS: The mean follow-up period was 61 (IQR=32-84) months. The median H-scores for FGFR-4 were higher in patients without remission, those with residual lesion, and T2-hyperintense adenoma (p<0.05). Ki-67 level was higher in patients without remission compared to those in remission (p<0.05). The mean Ki-67 levels did not differ between patients with and without residual lesion or T2-hyperintense tumor (p>0.05). There was no significant difference (p>0.05) when the H-score and Ki-67 levels were assessed in terms of sex, sellar-dural invasion, Knosp and a grading system for superior, inferior, parasellar, anterior and posterior tumor extension Classification, tumor function or presence of poor subtype. Adenomas with Ki-67 expression ≥3% had higher FGFR4 expression levels than those with <3% expression (p=0.002). There was a weak positive correlation between H-score and Ki-67 (p=0.011; r=0.201). CONCLUSIONS: Higher levels of FGFR-4 in pituitary adenomas could be use a marker for more aggressive tumor behavior.