Formation of internal carotid artery aneurysms following gamma knife radiosurgery for pituitary adenomas: a case series and literature review.

Only two aneurysm formations in the internal carotid artery after gamma knife radiosurgery (GKRS) for pituitary adenomas are reported so far. Here, out of the 482 patients who underwent GKRS for pituitary adenomas at our institute, at least five developed aneurysms within the area of high single-dose irradiation. Three patients presented with epistaxis due to aneurysmal rupture and one presented with abducens paralysis due to nerve compression, while one was asymptomatic. The interval between irradiation and aneurysmal detection ranged from 14 to 21 years. Aneurysm formation in those conditions may be higher than previously thought.

[A Multicenter Retrospective Study of Predictors of Duration of Treatment with Palbociclib].

Palbociclib(PAL), which is a small molecule with inhibitory activity against cyclin-dependent kinase 4/6, is used in endocrine combined therapy for the treatment of estrogen receptor(ER)-positive and HER2-negative inoperable and recurrent breast cancer. We retrospectively investigated the factors associated with prolonged treatment in inoperable and recurrent breast cancer in a multicenter study. The median time-to-treatment failure(TTF)after PAL was 5.6 months(0.2-22.5). A total of 28 patients in the fulvestrant(FUL)group and 21 patients in the aromatase inhibitor(AI)group received concomitant endocrine therapy. The median TTF was 2.6 vs 6.7 months(p=0.015)for white blood cell(WBC), 3.7 vs 6.6 months (p=0.021)for neutrophils(Neu), and 2.8 vs 7.5 months(p=0.007)for lymphocytes(Lym). The treatment period tended to be prolonged in the group with higher WBC, Neu, and Lym levels than that of the standard values. The median treatment duration of the FUL group was 7.5 months vs 4.2 months(p=0.162); however, the difference was not statistically significant. The WBC, Neu, and Lym levels upon PAL introduction may be factors affecting the prolonged treatment. Further analysis of the data and further investigation of the prolongation-related factors of PAL treatment period are necessary.

Aggressive Pituitary Adenoma Not Fulfilling the New High-Risk Criteria with Progression after 18-Year Stable Clinical Course: Case Report.

BACKGROUND: The World Health Organization (WHO) classification of tumors of the endocrine organs was revised in 2017. The term atypical adenoma is no longer recommended, and tumors with rapid growth, radiologic invasion, and high Ki-67 labeling index are defined as high-risk adenomas. In this article, we present the case of an aggressive pituitary adenoma not fulfilling the new high-risk criteria with extraordinary rapid progression after very long stable disease, and discuss the remaining problem of the new criteria in terms of a complicated balance between pathologic findings and clinical features. CASE DESCRIPTION: A 67-year-old man was admitted with sellar tumor. Serum prolactin concentration was high at 4,552.2 ng/mL. Transsphenoidal surgery achieved subtotal removal. Histologic diagnosis was lactotroph cell adenoma, and Ki-67 labeling index was 2.6%. Postoperatively, magnetic resonance imaging revealed no evidence of tumor regrowth, but terguride or cabergoline administration was continued for slight hyperprolactinemia. Second surgery was performed 18 years after initial surgery because the tumor showed extraordinary rapid regrowth and hyperprolactinemia of 969 ng/mL. Histologic diagnosis was lactotroph cell adenoma with Ki-67 labeling index of 28.9% and positive immunoreactivity for p53. This case could be diagnosed as a high-risk adenoma from the beginning of treatment based on the WHO 2017 criteria, but the clinical course was unusually long and the indication of aggressive adjuvant therapy after initial surgery remained unsolved. CONCLUSION: Pathologic confirmation for the present definition would be expected to assess the cutoff between typical adenomas and aggressive tumors.

Pituitary Adenomas Associated with Intracranial Aneurysms: the Clinical Characteristics, Therapeutic Strategies, and Possible Effects of Vascular Remodeling Factors.

BACKGROUND: Pituitary adenoma coexists with intracranial aneurysms in 2.3 to 3.6% of cases, and intracranial aneurysms are thought to be incidental. On the other hand, older age and cavernous sinus invasion are reported to increase the rate of coexistence, so these two diseases may be related. METHODS: Ten males and 14 females with the coexistence of pituitary adenomas and intracranial aneurysms were retrospectively investigated among 923 patients (2.6%). Patients were subdivided into two groups: those with direct attachment of cerebral aneurysms to the pituitary adenomas and those without direct attachment. The clinical characteristics, therapeutic strategies, and possible effects of vascular remodeling factors were investigated. RESULTS: Twelve patients had functioning pituitary adenomas, and cavernous sinus invasion was identified in 7 of 24 patients. Five of these 7 patients were treated with priority for the cerebral aneurysm until 2007, whereas 14 of 17 patients without involvement of the aneurysm tip in the tumor were treated with priority for the pituitary adenoma in the later period. Among vascular remodeling factors, strong expression of vascular endothelial growth factor (VEGF) was significantly associated with the coexistence of pituitary adenoma and cerebral aneurysm (p < 0.05). CONCLUSION: Intracranial aneurysms were found to coexist in 2.6% of cases of surgically treated pituitary adenomas. VEGF-induced arterial wall remodeling may be part of the mechanism of association between pituitary adenomas and cerebral aneurysms, suggesting possible causative mechanism.

Quantification of Tumor Blush of Highly Vascularized Tumors with Slow Feeding System: Representative Use for Giant Pituitary Adenomas.

BACKGROUND: Modern imaging techniques can identify adverse factors for tumor removal such as cavernous sinus invasion before surgery, but surgeries for giant pituitary adenomas often reveal discrepancies between preoperative imaging and intraoperative findings because pituitary adenomas have feeding arteries with narrow diameters. Current imaging methods are not suitable for tumors with not only large vascular beds but also slow arterial filling. PATIENTS AND METHODS: This prospective study recruited 13 male subjects and 9 female subjects with giant pituitary adenomas between November 2011 and 2018. All the patients were investigated with three-dimensional magnetic resonance (MR) imaging, bone image computerized tomography (CT), and digital subtraction angiography (DSA) using a C-arm cone-beam CT scanner with a flat-panel detector and 50% diluted contrast medium. Fine angioarchitecture was evaluated and the tumor blush was quantified using newly developed region of interest (ROI) analysis to establish surgical strategies. RESULTS: Seven patients demonstrated no or very faint tumor blushes. In these patients, feeding arteries run centripetally from the surface of the tumor. Fifteen patients showed significant tumor blushes, and the feeding arteries penetrated centrifugally from the inferoposterior pole to the upper pole of the tumor. All the patients were treated according to the angiographic information with successful hemostasis. The patients showed improvement and/or disappearance of the neurologic deficits. The faint and significant blush groups showed significant differences in intraoperative bleeding (p < 0.01) and operation time (p < 0.05). CONCLUSION: Specialized evaluation focused on vascularization is required for successful therapy of giant pituitary adenomas.

Treatment and therapeutic strategies for pituitary apoplexy in pregnancy: a case series.

BACKGROUND: Pregnancy is a known risk factor for pituitary apoplexy, which is life threatening for both mother and child. However, very few clinical interventions have been proposed for managing pituitary apoplexy in pregnancy. CASE PRESENTATION: We describe the management of three cases of pituitary apoplexy during pregnancy and review available literature. Presenting symptoms in our case series were headache and/or visual disturbances, and the etiology in all cases was hemorrhage. Conservative therapy was followed until 34 weeks of gestation, after which babies were delivered by cesarean section with prophylactic bolus hydrocortisone supplementation. Tumor removal was only electively performed after delivery using the transsphenoidal approach. All three patients and their babies had a good clinical course, and postoperative pathological evaluation revealed that all tumors were functional and that they secreted prolactin. CONCLUSIONS: Although the mechanism of pituitary apoplexy occurrence remains unknown, the most important treatment strategy for pituitary apoplexy in pregnancy remains adequate hydrocortisone supplementation and frequent hormonal investigation. Radiological follow-up should be performed only if clinical symptoms deteriorate, and optimal timing for surgical resection should be discussed by a multidisciplinary team that includes obstetricians and neonatologists.

Midterm prognosis and surgical implication for clival chordomas after extended transsphenoidal tumor removal and gamma knife radiosurgery.

BACKGROUND: Treating chordoma through surgery alone is often ineffective. Thus, surgery often performed with irradiation, with a reported 5-year survival rate of 60-75%. The clinical course varies, and disease rarity prevents larger number of clinical investigations. METHODS: In total, 19 patients with clival chordomas were retrospectively extracted from our institutional database. They were initially treated with maximal tumor removal using the extended transsphenoidal approach between March 2006 and January 2021. When total tumor removal was achieved, prophylactic irradiation was not performed. If tumor remnants or recurrence were confirmed, Gamma Knife (GK) radiosurgery was performed. The mean follow-up period was 106.7 months (ranged 27-224 months). The clinical course and prognostic factors were investigated. RESULTS: Total removal was achieved in 10 patients, whereas 4 patients suffered recurrence and required GK. GK was applied to 11 patients with a 50% isodose of 13-18 Gy (mean: 15.4 Gy), and eight patients remained progression free, whereas three patients suffered repeated local recurrence and died of tumor-related complications. The mean overall progression-free interval was 57.2 months (range: 6-169 months). One male patient died of tumor un-related lung cancer 36 months after the initial treatment, and other patients survived throughout the observational periods. The mean overall survival was 106.7 months (range: 27-224 months). Thus, the 5-year survival rate was 94.7%. Statistical analysis indicated that sex (men), > 15 Gy of 50% isodose by GK, and screening brain examinations as prophylactic medicine were significant favorable prognostic factors. CONCLUSIONS: The favorable outcomes in this investigation suggest the importance of early detection and treatment. Surgery may enable better conditions for sufficient GK doses.

A single- center experience of prolactin-producing pituitary adenomas without hyperprolactinemia: Its incidence and clinical management.

OBJECTIVE: This study clarifies the incidence of prolactin-producing pituitary adenomas without hyperprolactinemia and determines the appropriate treatment strategy for these tumors. PATIENTS AND METHODS: This retrospective analysis focused on prolactin-producing adenomas without hyperprolactinemia, which were initially treated by surgery as nonfunctioning pituitary adenomas. Among 942 patients with histologically confirmed pituitary adenoma, 114 (12.1 %) patients, consisting of 68 men and 46 women, who had prolactin-producing adenomas without hyperprolactinemia were identified between April 2005 and March 2019. RESULTS: Of the 114 patients identified, 13 (11.4 %) had prolactin mono-expressions, 18 (15.8 %) had pit-1 lineage hormonal expressions, and 83 (72.8 %) had paradoxical immunoexpression out of the pituitary differentiation lineage, including prolactin. During the follow-up period, 19 patients suffered tumor progression, and 14 required salvage treatment. Of the 19 patients, 11 underwent gamma knife radiosurgery, and none of them experienced further tumor progression. Cabergoline was administered of them to six patients, and one achieved tumor shrinkage. However, the remaining five patients who were treated with cabergoline suffered further tumor progression and required another salvage treatment. Among the patients in the prolactin mono-expression group, one experienced tumor regrowth and underwent gamma knife radiosurgery. In the pit-1 lineage group, two patients experienced tumor regrowth. One had further tumor progression after treatment with cabergoline and underwent gamma knife radiosurgery. Among the patients in the paradoxical immunoexpression group, 16 suffered tumor progression. Four patients underwent further surgery, seven patients were treated with gamma knife radiosurgery, and one patient received fractionated irradiation. None of the eight patients who were treated with gamma knife radiosurgery and fractionated irradiation showed further tumor progression. Four patients in this group were treated with cabergoline, but they all suffered further tumor progression and underwent additional salvage treatments. CONCLUSIONS: Out of the pituitary differentiation lineage, paradoxical hormonal expression occurred in three-quarters of the patients identified. Further surgery or gamma knife radiosurgery should be given priority in times of tumor progression because most patients were resistant to dopamine agonists.

Frequent Clinical and Radiological Progression of Optic Pathway/Hypothalamic Pilocytic Astrocytoma in Adolescents and Young Adults.

Most cases of optic hypothalamic pilocytic astrocytoma (OHPA) develop during childhood, so few cases of histologically verified OHPA have been described in adolescents and young adults (AYA). To elucidate the clinical features of OHPA with histological verification in AYA, we reviewed the clinical and radiological finding of OHPA treated at our institute from January 1997 and July 2017. AYA are aged between 15 and 39 years. The clinical courses of 11 AYA patients with optic hypothalamic glioma (OHG) without neurofibromatosis type 1 were retrospectively reviewed. About six patients were diagnosed in childhood and followed up after 15 years of age, and five patients developed OHPA during AYA. Histological diagnosis, verified at initial presentation or recurrence, was pilocytic astrocytoma in 10 and pilomyxoid astrocytoma in one. After initial treatment including debulking surgery and/or chemotherapy, tumor progression occurred 16 times in seven patients as cyst formation, tumor growth, and intratumoral hemorrhage. Five of 10 patients suffered deterioration of visual function during AYA. One of 10 cases had endocrinopathies requiring hormone replacement at last follow-up examination. In conclusion, histological diagnoses of OHG before and in AYA were pilocytic astrocytoma or pilomyxoid astrocytoma. Both pediatric and AYA-onset OHPA demonstrate high incidences of tumor progression and visual dysfunctions in AYA, so that long-term follow up is essential after the completion of treatment for pediatric and AYA-onset OHPA. The optimal timing of debulking surgery and radiation therapy should be established to achieve the long-term tumor control and to preserve the visual function.

Case reports of latent HBV hepatitis in patients after neurosurgical treatment for hypothalamic and pituitary tumors.

BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem worldwide. More than 2 billion people have been exposed to HBV, and about 257 million individuals are chronic carriers of HBV. HBV reactivation has been increasingly reported in HBV carriers who have undergone immunosuppression or chemotherapy, resulting in mortality. Treatment of hypothalamic/pituitary tumors in HBV carriers requires extensive care to avoid HBV reactivation as steroid therapy is required after surgery for hypothalamic/pituitary tumors. CASE PRESENTATION: This retrospective review identified 5 patients, who were HBV carriers positive for hepatitis B surface antigen among 1352 patients with surgically treated hypothalamic/pituitary tumor in Kohnan Hospital between February 2007 and April 2017. Transsphenoidal surgery was performed with particular attention to prevent damage to the pituitary gland, with delicate manipulation to minimize postoperative steroid coverage. All patients received nucleot(s)ide analogue to control HBV-DNA levels before the surgery. As a result, all patients had a good clinical course. Blood examinations found a transient increase of liver enzymes and HBV-DNA levels in all patients, which started to decrease within 2 weeks after surgery. No specific treatment other than nucleot(s)ide analogues was needed to maintain liver function, and all patients returned to their previous activities including reinstatement. CONCLUSION: Initiation of nucleot(s)ide analogues administration prior to the surgery for hypothalamic/pituitary tumors can be an effective strategy for preventing reactivation in HBV carriers. Appropriate screening of the patient's HBV phase, optimal timing of nucleot(s)ide analogues -administration, and administration period of nucleot(s)ide analogues need to be established.

Heterogeneity of Growth Hormone Receptor Expression in Craniopharyngioma-Implications for Surgical Strategy.

BACKGROUND: Recent molecular investigations for craniopharyngiomas have investigated possible predictive biologic markers. Growth hormone receptor (GHR) is thought to be involved in tumor aggressiveness, and high expression of GHR is associated with shorter duration of postoperative stable disease. CASE DESCRIPTION: A 27-year-old man with a large suprasellar tumor underwent an inexplicable clinical course. Transsphenoidal surgery achieved gross total removal of the tumor. Histologic diagnosis was adamantinomatous craniopharyngioma, and immunohistochemistry revealed very low GHR expression. He was discharged with multiple hormonal supplements except for growth hormone. Recurrence was detected 18 months later, and removal of the second tumor was performed with coagulation of the superior surface of the remaining pituitary gland. Growth hormone supplementation was started in the postoperative period, and he returned to work. However, a further recurrence was detected. Head magnetic resonance imaging showed almost the same pattern of tumor recurrence as preoperative imaging of the second surgery, and simultaneous removal of the tumor and the normal pituitary gland was performed. Reevaluation of histology revealed no morphologic differences between the first and the third surgical specimens, but immunohistochemical staining for GHR showed diffuse high expression in the third specimen. The difference was thought to reflect the heterogeneity of GHR, and appearance of histologic hot spots greatly affected the postoperative prognosis. CONCLUSIONS: Extensive removal of the possible tumor bed may be necessary for patients requiring growth hormone supplementation even after gross total removal of craniopharyngioma.

Hyaluronan promotes TRPV4-induced chondrogenesis in ATDC5 cells.

Hyaluronan (HA) is an extracellular matrix glycosaminoglycan essential for the homeostasis of cartilage-related tissues. Intracellular adhesion molecule-1 (ICAM-1) and CD44 have been identified as receptors for HA. Recently, transient receptor potential vanilloid 4 (TRPV4) has emerged as a potential research target in several areas of physiology. TRPV4 is a Ca2+-permeable, non-selective cation channel that appears to have mechanosensory or osmosensory roles in several musculoskeletal tissues. HA and TRPV4 play key roles in chondrogenesis; however, it has remained unclear whether they have interactive effects on chondrogenesis and, if so, how do they interact with each other? This study investigated the relationship between HA, its receptors ICAM-1 and CD44, and TRPV4 in the chondrogenic pathway using the ATDC5 cell line. It was found that the presence of HA is required for TRPV4-induced chondrogenesis. Loss of HA suppressed TRPV4-induced expression of the chondrogenic markers, SOX9 and Aggrecan. Moreover, HA affects TRPV4-induced chondrogenic development via each of ICAM-1 and CD44 partially. In conclusion, for the first time, the existence of an interaction between HA, its receptor ICAM-1 and CD44, and TRPV4-activity in chondrogenesis in the ATDC5 cell line was reported. TRPV4 is known to function as a mechanosensory channel in several musculoskeletal tissues. Therefore, findings of this study may suggest the existence of a molecular mechanism that underlies the interactive effects of HA and mechanical loading on joint chondrogenesis.

Partial Reconstitution of the Hypothalamo-Pituitary Axes After Pituitary Stalk Sectioning and Specific Magnetic Resonance Imaging Findings.

BACKGROUND: Pituitary stalk sectioning is only essential in cases of craniopharyngioma originating from the stalk or metastatic tumor to the stalk. Some patients can discontinue postoperative antidiuretic hormone (ADH) supplementation with special conditions. METHODS: Sixty-three patients with craniopharyngiomas who were treated by surgery with pituitary stalk sectioning were included in this study. Great care was taken to preserve the fine arteries running along the lateral walls of the third ventricle. Removal rates, change of endocrinologic status, and magnetic resonance imaging (MRI) findings were investigated. RESULTS: Total removal was achieved in 52 of 54 patients in initial surgery (96.3%), and in 5 of 9 patients in retreatment (55.6%). ADH supplementation was required in all patients from the day of surgery, but was discontinued in 29 of 54 patients among the initial surgery group (53.7%) and in 2 of 9 patients among the retreatment group (22.2%). Preservation of thyroid hormone secretion was observed in 24 of 31 patients who could discontinue ADH (77.4%), but only in 12 of 32 patients who could not discontinue ADH (37.5%). Recovery from diabetes insipidus (DI) was significantly associated with preservation of thyroid function (P < 0.01). Postoperative MRI showed that part of the hypothalamus was enhanced in patients with recovery from DI. CONCLUSIONS: Total removal was achieved in 91% of all cases. Half of the patients could discontinue ADH supplementation, which was associated with preservation of thyroid function. The findings of hypothalamic enhancement on postoperative MRI may be associated with recovery from DI.

Massive Intramedullary Hemorrhage After Subarachnoid Hemorrhage in Patient with Vertebrovertebral Arteriovenous Fistula.

BACKGROUND: Hemorrhagic presentations are rare in vertebrovertebral arteriovenous fistula (VVAVF). To the best of our knowledge, this is the first report of a patient initially presenting with subarachnoid hemorrhage and progressing to intramedullary hemorrhage. CASE DESCRIPTION: The authors report on a 59-year-old man with VVAVF who developed massive intramedullary hemorrhage. Twelve months before ictus, the patient presented with subarachnoid hemorrhage. Although we recommended endovascular surgery, the patient refused treatment. Twelve months after the initial attack, the massive intramedullary hemorrhage in cervical spinal cord caused complete spinal cord injury. Emergent endovascular intervention was performed after the intramedullary hemorrhage, but there was no neurologic improvement. CONCLUSIONS: Identification of this phenomenon is important in VVAVF because intramedullary hemorrhage dramatically degrades patient outcome. Prompt surgical intervention is mandatory for VVAVF cases presenting with subarachnoid hemorrhage.

Association between seropositivity and discontinuation of tumor necrosis factor inhibitors due to ineffectiveness in rheumatoid arthritis.

INTRODUCTION/OBJECTIVES: Discontinuation of biologic therapy in rheumatoid arthritis is attributable to various reasons, with the most important cause being insufficient response. In this study, we investigated the association between rheumatoid factor (RF) and anti-citrullinated protein autoantibody (ACPA) status and the discontinuation of tumor necrosis factor inhibitors (TNFi) therapy due to insufficient response in bio-naïve rheumatoid arthritis (RA) patients. METHOD: This study included patients enrolled in the Tsurumai Biologic Communication Registry in Japan. The crude comparison of TNFi discontinuation due to ineffectiveness between seropositive and seronegative patients was analyzed using the cumulative incidence function of competing events and Gray test. We assessed the associations between baseline patient characteristics and discontinuation of TNFi therapy due to insufficient response using Fine-Gray proportional hazard regression. Fine-Gray proportional hazard analysis considered competing events of interest, including insufficient response, adverse event, palliation, and personal reasons. RESULTS: Of 1237 patients evaluated, 79.3% were positive for RF and 85.4% for ACPA; 72.6% were double positive and 11.1% were double negative. TNFi therapy had been discontinued because of insufficient response at 200 weeks in 19.8% RF-positive, 16.7% RF-negative, 23.0% ACPA-positive, and 13.8% ACPA-negative patients. There was a significantly higher discontinuation rate due to insufficient response in ACPA-positive patients than in ACPA-negative patients using Gray test, with a similar trend as that for RF status. RF positivity was significantly predictive of the discontinuation of TNFi therapy due to ineffectiveness using Fine-Gray proportional hazard regression analysis after adjusting for baseline characteristics, including age, sex, stage, class, disease activity at baseline, methotrexate use, and prednisolone use [hazard ratio 1.73 (95% confidence interval 1.07-2.80)]. CONCLUSIONS: Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients. Key Points • RF positivity is related to a higher discontinuation rate of TNFi therapy due to ineffectiveness. • ACPA is not predictive of a discontinuation of TNFi therapy due to ineffectiveness.

Association between chronic kidney disease and synergistic, potentially nephrotoxic medication use in elderly hospitalized patients: A single-center cross-sectional study
.

OBJECTIVE: In elderly patients, age-related, disease-related, and drug-related factors are associated with chronic kidney disease (CKD). Little is known about which factors are the best predictors for CKD in elderly patients. MATERIALS AND METHODS: The study was based on 784 patients aged 75 years or older for whom the clinical and serum creatinine on admission to our hospital were available. Impaired renal function, including CKD and transient renal insufficiency, was defined as a non-indexed glomerular filtration rate (GFR) below 60 mL/min. A logistic regression model was developed for predictors of CKD and was internally validated using bootstrapping. RESULTS: Approximately 61% of the patients, who had CKD (46%) and transient renal insufficiency (15%), had a non-indexed GFR < 60 mL/min. Synergistic use of 3 drugs potentially impairing renal function, diuretics, ACE-I/ARB, and NSAIDs (odds ratio (OR), 4.66; 95% confidence interval (CI), 1.48 - 17.7, p = 0.012) was a significantly associated factor for CKD in a multivariate logistic regression analysis. Age (OR 1.56, 95% CI 1.04 - 2.33, p = 0.03), female gender (OR 1.58, 95% CI 1.04 - 2.39, p = 0.03), any prescription ACE-I/ARB either alone or in combinations with diuretics or NSAIDs (OR 2.74, 95% CI 1.83 - 4.13, p = 0.0001), and proteinuria (OR 1.98, 95% CI 1.27 - 3.10, p = 0.003), were included as the best model for CKD. The area under the curve (AUC) of the best model and the bootstrapping validation were 0.68 and 0.71, respectively. CONCLUSION: Given the widespread use of ACE-I/ARB for elderly patients, our findings suggest that caution is needed when they are prescribed because of the possibility of the patient developing CKD.

Early surgical intervention for patients with possible clinically silent somatotroph adenoma: a case series.

INTRODUCTION: Clinically silent somatotroph adenoma is characterized by elevated serum growth hormone but without the clinical symptoms of acromegaly, and it is considered rare. The natural history is not well understood, progress to symptomatic is uncertain, and treatment strategy has not been established. CASE PRESENTATION: The first patient was a 48-year-old-Asian woman who presented with serum growth hormone 6.99 ng/ml and insulin-like growth factor 1 of 476 ng/ml, but no characteristic features of acromegaly. Five years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The second patient was a 40-year-old-Asian woman who presented with serum growth hormone 31.14 ng/ml and insulin-like growth factor 1 of 709.6 ng/ml, but no characteristic features of acromegaly. Three years after initial diagnosis, she presented with acromegalic facial appearance. Transsphenoidal surgery achieved gross total removal and endocrinological remission. The third patient was a 64-year-old-Asian woman who presented with serum growth hormone 6.0 ng/ml and insulin-like growth factor 1 of 341 ng/ml, but no characteristic features of acromegaly. Eight months after initial diagnosis, hand enlargement was detected. Transsphenoidal surgery achieved gross total removal and endocrinological remission. CONCLUSION: Due to its potential for evolving to symptomatic disease, the risks of surgery and observation for patients with somatotroph adenoma should be carefully compared from the viewpoint of better health outcome.

Retinal Nerve Fiber Layer Thickness Measurement for Predicting Visual Outcome after Transsphenoidal Surgery: Optic Disc Atrophy Is Not the Deciding Indicator.

BACKGROUND: Postoperative visual recovery is a major concern after transsphenoidal surgery. Optical coherence tomography (OCT) can visualize the anatomy of the retina, and retinal nerve fiber layer (RNFL) thinning reflects loss of optic nerve axons. Visual-evoked potential (VEP) is an electrophysiological response that confirms the nerve conductance. Therefore, these factors reflecting the optic nerve condition may be closely associated with the visual outcome after transsphenoidal surgery. METHODS: A total of 124 eyes in 62 patients with sellar tumor who underwent transsphenoidal surgery were included. The following variables were retrospectively analyzed: age, sex, tumor diameter, histology, symptom duration, history of rapid deterioration, optic disc atrophy on fundoscopy, peripapillary RNFL thickness on OCT, and latency and reproducibility of the VEP waveform. RESULTS: Four eyes were excluded for no visual disturbance in 3 and glaucoma aggravation in 1. Eighty-three eyes manifested visual improvement, 37 revealed no change, and none showed postoperative deterioration. Univariate analysis demonstrated that thick RNFL of the inferior and temporal quadrants, reproducible VEP waveform, short symptom duration, histologic diagnosis of pituitary adenoma, and small tumor diameter were associated with good visual recovery. Multivariate analysis showed RNFL thickness of the temporal quadrant had significant association with visual recovery (P = 0.03). CONCLUSIONS: OCT is a useful diagnostic modality to assess optic nerve condition, and RNFL thickness of the temporal quadrant is correlated with visual outcome after transsphenoidal surgery. Patients with severe visual disturbance may still achieve visual recovery, so surgery should be considered even if optic disc atrophy is evident.

Transsphenoidal Removal of Retroclival Chondroma with Pituitary Transposition Manifesting as Repeated Subarachnoid Hemorrhage: A Case Report.

BACKGROUND: Intracranial chondromas are extremely rare and represent only 0.2% of all intracranial primary neoplasms. The histologic appearance lacks nuclear atypism and mitoses, and it usually shows low growth potential, although these benign features do not necessarily imply a good prognosis. CASE DESCRIPTION: A 44-year-old man was referred to our institution with a subarachnoid hemorrhage (SAH). He had a history of SAH 5 years previously that was diagnosed as unknown etiology at another hospital. Head magnetic resonance imaging showed a large tumor located in the prepontine cistern and extending up to the interpeduncular cistern, and the tumor was irregularly enhanced with contrast medium. Retrospective analysis of the original computed tomography of 5 years earlier identified a small contrast enhancing defect behind the dorsum sellae. Tumor removal was planned to prevent repeated SAH and control the apparently growing tumor. An extended transsphenoidal approach was performed. The pituitary gland was dissected from the bottom of the sellar floor and transposed forward to the prechiasmatic cistern with preservation of the pituitary stalk and its blood supply, and subtotal removal of the tumor was achieved. Postoperative diabetes insipidus disappeared within a few days, and the patient was discharged without neurologic or endocrinologic deficits. Histologic examination established the diagnosis as chondroma without a sarcomatous component. Follow-up examination 3 months after surgery showed a re-enlargement of the residual tumor, and gamma knife surgery was performed. CONCLUSIONS: Intracranial chondroma sometimes manifests as intracranial hemorrhage and grows comparatively rapidly in a short period despite the benign histologic features. A long and careful follow-up period is essential.

[Surgical Planning for a Giant Pituitary Adenoma Based on Evaluation of the Fine Feeding System and Angioarchitecture:A Case Report].

Giant pituitary adenomas carry higher surgical risks despite recent advances in microsurgical and/or endoscopic surgery. In particular, postoperative acute catastrophic changes without major vessel disturbance are still extremely difficult to predict, and may manifest as postoperative pituitary apoplexy with very poor outcomes. These changes are associated with injuries to the capillary intratumoral feeders and/or drainers, which frequently have diameters of less than 300µm, and result in drastic hemodynamic changes. A 43-year-old woman with severe visual disturbance and a giant pituitary adenoma was referred to our institute, The tumor had extended irregularly toward the suprasellar cistern and had compressed the optic chiasm upwards, and the bilateral frontal lobes were displaced laterally. Surgery was planned based on information regarding the fine angioarchitecture and feeding systems using a C-arm cone-beam CT scanner with a flat-panel detector(GE Healthcare;IL, USA)and 50%-diluted contrast medium, which disclosed the distinct feedings from the left meningohypophyseal trunk to the left lower part of the tumor and from the left superior hypophyseal artery to the upper posterior part, and absence of pial blood supply to the lateral pole of the tumor. Extended transsphenoidal surgery was performed and achieved total tumor removal. The patient was discharged without neurological or endocrinological deficits. Detailed preoperative examination of the feeding system and hemodynamics of giant pituitary adenomas is not a priority at present. However, we would like to emphasize the need for specific individual operative strategies to prevent devastating outcomes after surgery for this formidable tumor.