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Context: Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion, mostly induced by pituitary adenomas. The care of pregnant women with acromegaly is challenging, in part due to existing clinical data being limited and not entirely consistent with regard to potential risks for mother and child., Objective: To retrospectively examine data on pregnancy and maternal as well as neonatal outcomes in patients with acromegaly., Design & Methods: Retrospective data analysis from 47 pregnancies of 31 women treated in centers of the German Acromegaly Registry., Results: 87.1% of the studied women underwent transsphenoidal surgery before pregnancy. In 51.1% a combination of dopamine agonists and somatostatin analogs were used before pregnancy. Three women did not receive any therapy for acromegaly. During pregnancy only 6.4% received either somatostatin analogs or dopamine agonists. In total, 70.2% of all documented pregnancies emerged spontaneously. Gestational diabetes was diagnosed in 10.6% and gravid hypertension in 6.4%. Overall, no preterm birth was detected. Indeed, 87% of acromegalic women experienced a delivery without complications., Conclusion: Pregnancies in women with acromegaly are possible and the course of pregnancy is in general safe for mother and child both with and without specific treatment for acromegaly. The prevalence of concomitant metabolic diseases such as gestational diabetes is comparable to the prevalence in healthy pregnant women. Nevertheless, larger studies with more data in pregnant patients with acromegaly are needed to provide safe and effective care for pregnant women with this condition., (© 2024. The Author(s).)

Objective: First-line prolactin-secreting tumor (PST) management typically involves treatment with dopamine agonists and the role of surgery remains to be further explored. We examined the international experience of 12 neurosurgical centers to assess the patient characteristics, safety profile, and effectiveness of surgery for PST management., Methods: Patients surgically treated for PST from January 2017 through December 2020 were evaluated for surgical characteristics, outcomes, and safety., Results: Among 272 patients identified (65.1% female), the mean age was 38.0 ± 14.3 years. Overall, 54.4% of PST were macroadenomas. Minor complications were seen in 39.3% of patients and major complications were in 4.4%. The most common major complications were epistaxis and worsened vision. Most minor complications involved electrolyte/sodium dysregulation. At 3-6 months, local control on imaging was achieved in 94.8% of cases and residual/recurrent tumor was seen in 19.3%. Reoperations were required for 2.9% of cases. On multivariate analysis, previous surgery was significantly predictive of intraoperative complications (6.14 OR, p < 0.01) and major complications (14.12 OR, p < 0.01). Previous pharmacotherapy (0.27 OR, p = 0.02) and cavernous sinus invasion (0.19 OR, p = 0.03) were significantly protective against early endocrinological cure. Knosp classification was highly predictive of residual tumor or PST recurrence on 6-month follow-up imaging (4.60 OR, p < 0.01). There was noted institutional variation in clinical factors and outcomes., Conclusion: Our results evaluate a modern, multicenter, global series of PST. These data can serve as a benchmark to compare with DA therapy and other surgical series. Further study and longer term outcomes could provide insight into how patients benefit from surgical treatment., Competing Interests: Declaration of Competing Interest The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article. Henry W.S. Schroeder has a financial relationship with Karl Storz SE & Co. KG., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Crooke cell adenomas (CCAs) are a rare, aggressive subset of secretory pituitary corticotroph adenomas (sCTAs) found in 5%-10% of patients with Cushing disease. Multiple studies support worse outcomes in CCAs but are limited by small sample size and single-institution databases. We compared outcomes in CCA and sCTA using a multicenter, international retrospective database of high-volume skull base centers., Methods: Patients surgically treated for pituitary adenoma from January 2017 through December 2020 were included., Results: Among 2826 patients from 12 international centers, 20 patients with CCA and 480 patients with sCTA were identified. No difference in baseline demographics, tumor characteristics, or postoperative complications was seen. Microsurgical approaches (60% CCA vs. 62.3% sCTA) were most common. Gross total resection was higher in CCA patients (100% vs. 83%, P = 0.05). Among patients with gross total resection according to intraoperative findings, fewer CCA patients had postoperative hormone normalization of pituitary function (50% vs. 77.8%, P < 0.01) and remission of hypersecretion by 3-6 months (75% vs. 84.3%, P < 0.01). This was the case despite CCA having better local control rates (100% vs. 96%, P < 0.01) and fewer patients with remnant on magnetic resonance imaging (0% vs. 7.2%, P < 0.01). A systematic literature review of 35 studies reporting on various treatment strategies reiterated the high rate of residual tumor, persistent hypercortisolism, and tumor-related mortality in CCA patients., Conclusions: This modern, multicenter series of patients with CCA reflects their poor prognosis and reduced postsurgical hormonal normalization. Further work is necessary to better understand the pathophysiology of CCA to devise more targeted treatment approaches., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery., Methods: To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed., Results: Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (β = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach., Conclusion: Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Importance: Benchmarks aid in improve outcomes for surgical procedures. However, best achievable results that have been validated internationally for transsphenoidal surgery (TS) are not available., Objective: We aimed to establish standardized outcome benchmarks for TS of pituitary adenomas., Design: A total of 2685 transsphenoidal tumor resections from 9 expert centers in 3 continents were analyzed., Setting: Patients were risk stratified, and the median values of each center's outcomes were established. The benchmark was defined as the 75th percentile of all median values for a particular outcome. The postoperative benchmark outcomes included surgical factors, endocrinology-specific values, and neurology-specific values., Results: Of 2685 patients, 1149 (42.8%) defined the low-risk benchmark cohort. Within these benchmark cases, 831 (72.3%) patients underwent microscopic TS, and 308 (26.8%) patients underwent endoscopic endonasal resection. Of all tumors, 799 (29.8%) cases invaded the cavernous sinus. The postoperative complication rate was 19.6% with mortality between 0.0% and 0.8%. Benchmark cutoffs were ≤2.9% for reoperation rate, ≤1.9% for cerebrospinal fluid leak requiring intervention, and ≤15.5% for transient diabetes insipidus. At 6 months, benchmark cutoffs were calculated as follows: readmission rate: ≤6.9%, new hypopituitarism ≤6.0%, and tumor remnant ≤19.2%., Conclusions: This analysis defines benchmark values for TS targeting morbidity and mortality and represents the best outcomes in the best patients in expert centers. These cutoffs can be used to assess different centers, patient populations, and novel surgical techniques. It should be noted that the benchmark values may influence each other and must be evaluated in their own context., Competing Interests: Conflict of interest: The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background:  We compare the effect of urokinase (urokinase-type plasminogen activator [uPA]) versus alteplase (recombinant tissue plasminogen activator [rt-PA]) for intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) on ventriculoperitoneal shunt (VPS) dependence, functional outcome, and complications in the management of IVH., Methods:  We retrospectively reviewed the patients admitted with IVH or intracerebral hemorrhage (ICH) with IVH within 7 years in three different departments and found 102 patients who met the inclusion criteria. The primary end points were VPS dependence and Glasgow outcome score (GOS) at 3 months. Secondary end points were rate of rebleeding under IVF and incidence of treatment-related complications. Patients were divided into three groups: group I comprised patients treated with external ventricular drain (EVD) and IVF with uPA; group II comprised patients treated with EVD and IVF with rt-PA; and group III comprised patients treated with EVD alone., Results:  In all, 9.8% patients needed VPS: 12.2% in group I and 15.0% in group II, with no statistically significant difference. VPS patients had higher values of the modified Graeb score (mGS), IVH score, and IVH volume. We saw a trend for a better outcome in group II, with six patients achieving a GOS of 4 or 5 after 3 months. The mortality rate was higher in groups I and III. We found no statistical difference in the complication rate between groups I and II. Logistic regression analysis revealed that higher mGS and age predicted worse prognosis concerning mortality. The risk for death rose by 7.8% for each year of age. Any additional mGS point increased the chances of death by 9.7%., Conclusion:  Our data suggest that both uPA and rt-PA are safe and comparable regarding incidence of communicating hydrocephalus, and age and mGS are predictive for mortality., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose/objective: Multiple tumorous lesions in one pituitary gland are rare and mostly described in case reports. Their incidences and combinations are defined in larger collectives. Therefore, we analyzed our large collection for double tumors and combinations of tumors, cysts, and inflammation., Methods: The German Registry of Pituitary Tumors, including cases from 1990 to 2018, served as the database. Our collection comprises a total of 16,283 cases up until the end of 2018. Of these cases, 12,673 originated from surgical and 3,610 from autopsy material. All specimens were fixed in formalin and embedded in paraffin. The sections were stained with hematoxylin-eosin and PAS. Monoclonal (prolactin, TSH, FSH, LH, and α subunit) or polyclonal (GH and ACTH) antibodies were used to detect pituitary hormones in the lesions. Since 2017, antibodies against the transcription factors Pit-1, T-Pit, and SF-1 have been used in difficult cases. The criteria of the 2017 WHO classification have been basic principles for classification since 2018 (Osamura et al. 2017). For differentiation of other sellar tumors, such as meningiomas, chordomas, or metastases, the use of additional antibodies was necessary. For these cases, it was possible to use a broad antibody spectrum. Autopsy pituitaries were generally studied by H&E and PAS sections. If any lesions were demonstrated in these specimens, additional immunostaining was performed., Results: Multiple tumorous lesions with more than one pituitary neuroendocrine tumor (PitNET) respectively adenoma make up 1.4% (232 cases) in our collection. Within the selected cases, synchronous multiple pituitary neuroendocrine tumors (PitNETs) account for 17.3%, PANCH cases (pituitary adenoma with neuronal choristoma) for 14.7%, PitNETs and posterior lobe tumors for 2.2%, PitNETs and metastases for 5.2%, PitNETs and mesenchymal tumors for 2.6%, PitNETs and cysts for 52.2%, and PitNETs and primary inflammation for 6.0%. The mean patient age was 53.8 years, with a standard deviation of 18.5 years. A total of 55.3% of the patients were female and 44.7% were male. From 1990 to 2018, there was a continuous increase in the number of multiple tumorous lesions., Conclusion: From our studies, we conclude that considering possible tumorous double lesions during surgeries and in preoperative X-ray analyses is recommended., (© 2022. The Author(s).)

Objective: To identify early available predictors for the long-term outcome of patients after transsphenoidal surgery (TSS) in the management of Cushing's disease., Methods: This single-center, retrospective study included 93 consecutive patients with Cushing's disease (follow-up 12-129 months, mean 48, median 38) who underwent TSS (21 had previous operations elsewhere). Six cases had early re-operation, and the resulting data were evaluated instead of the respective first operation. During the postoperative course, serum cortisol levels were assessed every four hours at least until the next morning. An association of parameters with long-term outcomes was tested using binary logistic regression. Receiver operating characteristic curves were used to determine sensitivity, specificity, positive predictive value, and negative predictive value of different cut-off values of serum cortisol in the postoperative course in the event of recurrence after remission., Results: Eighty out of 93 patients (86%) showed postoperative remission (after primary treatment, 60 out of 72 patients, 90.3%). Of these, 8 patients (10%) developed recurrence of hypercortisolism. Compared to patients with persisting long-term remission, those with recurrence differed in cortisol levels starting from 4 pm on the day of surgery plus an event of increasing cortisol during the early postoperative course ("peak"). Binary logistic regression showed the association between a peak of serum cortisol in the early postoperative course with an increased probability of recurrence., Conclusions: Patients with a peak of serum cortisol in the early postoperative course show an increased recurrence rate. A cut-off value of serum cortisol for clear identification of patients with later recurrence could not be determined., Competing Interests: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Thieme. All rights reserved.)

Background: In patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes., Methods: This individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE)., Results: Comparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome., Conclusions: As compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Inflammatory pituitary lesions account for 1.8% of all specimens from the German Pituitary Tumor Registry. They occure in 0.5% of the autoptical specimens and in 2.2% of the surgical cases. Women are significantly more often affected than men and are often younger when first diagnosed. In general, primary and secondary inflammation can be distinguished, with secondary types occurring more frequently (75.1%) than idiopathic inflammatory lesions (15.4%). In primary inflammation, the lymphocytic type is more common (88.5%) than the granulomatous type of hypophysitis (11.5%). The most common causes of secondary inflammation are Rathke's cleft cysts (48.6%), followed by tumors (17.4%) such as the craniopharyngioma (9.1%), adenoma (5.5%) or germinoma (2.0%). More causes are tumor-like lesions (7.1%) such as xanthogranuloma (3.5%) or Langerhans histiocytosis (3.5%), abscesses (5.5%), generalized infections (5.1%), spreaded inflammations (4.7%) and previous surgeries (4.0%). In 1.6% of all specimens the reason for the inflammation remains unclear. The described classification of hypophysitis is important for specific treatment planning after surgery., (© 2021. The Author(s).)

Purpose: Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.5-1.5% of surgical specimens and in up to 10% of autopsy cases, two or three seemingly separate PA may coincide. These multiple adenomas may express different hormones, but whether or not expression of lineage-restricted transcription factors and molecular features are distinct within multiple lesions remains unknown., Methods: Searching the data bank of the German Pituitary Tumor Registry 12 double pituitary adenomas with diverse lineage were identified among 3654 adenomas and 6 hypophyseal carcinomas diagnosed between 2012 and 2020. The double adenomas were investigated immunohistochemically for expression of hormones and lineage markers. In addition, chromosomal gains and losses as well as global DNA methylation profiles were assessed, whenever sufficient material was available (n = 8 PA)., Results: In accordance with the literature, combinations of GH/prolactin/TSH-FSH/LH adenoma (4/12), GH/prolactin/TSH-ACTH adenoma (3/12), and ACTH-FSH/LH adenoma (3/12) were observed. Further, two out of 12 cases showed a combination of a GH/prolactin/TSH adenoma with a null-cell adenoma. Different expression pattern of hormones were confirmed by different expression of transcription factors in 11/12 patients. Finally, multiple lesions that were molecularly analysed in 4 patients displayed distinct copy number changes and global methylation pattern., Conclusion: Our data confirm and extend the knowledge on multiple PA and suggest that such lesions may origin from distinct cell types., (© 2021. The Author(s).)

Between 1996 and 2020, 12,565 cases were enrolled in the German Registry of Pituitary Tumors including 10,084 PitNETs (10,067 adenomas and 19 carcinomas obtained surgically and 193 adenomas diagnosed at autopsy) as well as 69 spindle cell tumors of the neurohypophysis (64 surgical specimens and 5 autopsies). In six patients (1 post mortem and 5 surgical specimens), PitNETs as well as posterior lobe tumors were found in the specimens. Two of the PitNETs were sparsely granulated prolactin-producing tumors, combined in one case with a granular cell tumor and in one case with a pituicytoma. One of the PitNETs revealed that autopsy was a sparsely granulated GH tumor combined with a neurohypophyseal granular cell tumor. Two PitNETs were null cell adenomas combined with a pituicytoma and a spindle cell oncocytoma, respectively. Further, one Crooke cell tumor was combined with a spindle cell oncocytoma. In five cases, the PitNETs were larger than the posterior lobe tumors and accounted for the clinical symptoms. Previously, four cases of co-existing pituitary anterior and posterior lobe tumors were described in the literature, comprising two ACTH PitNETs, one gonadotrophic PitNET and one null cell PitNET, each in combination with a pituicytoma. PitNETs and concomitant granular cell tumor or spindle cell oncocytoma, as observed in our cohort, have not been reported before., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: The authors have no competing interests to declare.

Background: The increasing use of cranial tomographic imaging has led to the more frequent discovery of pituitary tumors. In this review, we discuss the clinical symptoms that point toward a pituitary tumor, the required diagnostic studies, the potential need for follow-up studies, and the indications for neurosurgical treatment., Methods: This review is based on pertinent publications from the years 2005-2020 that were retrieved by a selective search in PubMed, as well as on the current German S2k guideline, which was created with the present authors playing a coordinating role, and on further guidelines from abroad. Relevant information from older reviews was also considered., Results: The reported prevalence of pituitary tumors varies depending on the method of data acquisition. Autopsy studies yield a figure of 10.7%, while population-based studies reported 77.6-115.6 cases per 100 000 inhabitants. These lesions are nearly always benign, and 85% of them are pituitary adenomas. Pituitary adenomas measuring less than 1 cm in diameter are called microadenomas, while those measuring 1 cm or more are called macroadenomas. According to magnetic resonance imaging (MRI) studies, the prevalence of microadenomas in the general population is in the range of 10-38%, while that of macroadenomas is 0.16-0.3%. Pituitary adenomas can be either hormonally inactive or hormonally active. Half of all patients with hormonally inactive microadenomas display no endocrine abnormality, while 37-85% of patients with hormonally inactive macroadenomas manifest at least partial pituitary insufficiency. The clinical spectrum of pituitary tumors ranges from a fully asymptomatic state to visual disturbances, neurologic deficits, severe hormone excess (e.g., in Cushing disease), and life-threatening pituitary insufficiency. Pituitary adenomas are often diagnosed only after a latency of many years, even when they are symptomatic. If an imaging study shows the tumor to be in contact with the visual pathway, an ophthalmological evaluation should be performed. There are clear indications for surgery, e.g., imminent loss of vision, but most asymptomatic pituitary tumors can be observed only., Conclusion: The manifestations of pituitary tumors are first recognized by primary care physicians. The further diagnostic evaluation of these patients should be carried out in standardized and interdisciplinary fashion.

Context: Acromegaly is a rare disease caused by excessive growth hormone (GH) secretion from pituitary adenomas in most cases. If neurosurgical therapy is contraindicated or not sufficient, medical therapy is the second line therapy., Objective: To describe current medical therapy in acromegaly., Design & Methods: Retrospective data analysis from 2732 patients treated in 69 centers of the German Acromegaly Registry. 749 patients were seen within the recent 18 months, of which 420 were on medical therapy (56.1%)., Results: 73% of medically treated acromegalic patients had normal/low IGF-1 levels. 57% of patients with non-normalized IGF-1 levels had an IGF-1 value between 1- and 1.25-fold above the upper limit of normal. Most patients (55%) received somatostatin analogs as monotherapy, 12% GH receptor monotherapy, and 9% dopamine agonist therapy. Doses of each medical therapy varied widely, with 120 mg lanreotide LAR every 4 weeks, 30 mg octreotide LAR every 4 weeks, 140 mg pegvisomant per week and 1mg cabergoline per week being the most frequent used regimens. A combination of different medical regimens was used in almost 25% of the patients., Conclusion: The majority of German acromegalic patients receiving medical therapy are controlled according to normal IGF-1 levels., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Brucellosis is a frequent zoonosis in some regions of the world and may cause various symptoms. Neurobrucellosis is a rare but serious complication of the infection. Our case report describes the course of neurobrucellosis in a patient who had received a ventriculoperitoneal shunt in his native country 13 years prior to diagnosis of brucellosis. He initially presented to us with symptoms of peritonitis, which misled us to perform abdominal surgery first. After the diagnosis of neurobrucellosis was confirmed and appropriate antibiotics were initiated, the symptoms soon disappeared. Although the ventriculoperitoneal shunt was subsequently removed, the patient did not develop a symptomatic hydrocephalus further on. This case displays the challenges in diagnosing an infection that occurred sporadically in Europe and may be missed by currently applied routine microbiological workup. Considering the political context, with increasing relocation from endemic areas to European countries, it is to be expected that the cases of brucellosis and neurobrucellosis will rise. Brucellosis should be considered and adequate investigations should be performed., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Transsphenoidal surgery for sellar lesions may affect patency and function of the nasal airways, smell and sinonasal quality of life. Below is our report on otorhinolaryngological data garnered from patients undergoing endonasal transsphenoidal pituitary microsurgery., Methods: In a prospective study, 68 patients scheduled for transsphenoidal operations (32 female, 36 male, age 17-72 years) underwent otorhinolaryngological evaluation of their nasal morphology, a standardized smell test (sniffin' sticks) and rhinomanometry to analyse nasal breathing function preoperatively, 3-5 days postoperatively (without rhinomanometry), after 3-4 months and after 9 months., Results: Immediately after surgery, a reduction in smell sensation was detected in almost all patients. Within 3 months, this impairment resolved in all cases except one. In 2 patients (3%) with preoperative anosmia, improvement of smell function to>6 out of 12 sniffin' sticks was observed. At final visit no patient was noted to have new anosmia. Within 3 months, the results of the rhinomanometry revealed that all patients except one, regained their preoperative nasal breathing function. In 6 patients (8.8%) an improvement in their nose breathing abilities compared to the preoperative state was found. Three patients (4.4%) underwent a LASER transection of mucosal synechiae. In one case with persistent nasal obstruction (1.5%), secondary septoplasty had to be performed. There was no case in which perforation of the nasal septum, nasal tip deflection, or saddle nose deformity was observed., Conclusion: Microsurgical resection of pituitary tumors via the endonasal transsphenoidal approach poses an acceptable risk with regards to sinonasal complications. The incidence of secondary rhinosurgical interventions is low. Standardized comparative studies between endoscopic and microsurgical transsphenoidal operations should be undertaken., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background:  The long-term outcome of facet joint replacement (FJR) still is to be proven., Methods:  We present a prospective case series of 26 (male-to-female ratio of 1:1; mean age: 61 years) patients undergoing FJR with a follow-up of at least 1 year (range: 12-112; mean: 67 months). Visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and the 12-Item Short Form Health Survey (SF-12) were applied pre- and postoperatively (after 3, 6, and 12 months) as well as at the last follow-up ( N  = 24). Using X-rays of the lumbar spine ( N  = 20), the range of motion (ROM) and disk height in the indicator and adjacent levels were assessed., Results:  FJR was performed at L3/L4 ( N  = 7), L4/L5 ( N  = 17), and L5/S1 ( N  = 2). Mean VAS (mm) for back pain decreased from 71 to 18, mean VAS for right leg pain from 61 to 7, and from 51 to 3 for the left leg. Mean ODI dropped from 51 to 22% (for all p  < 0.01). Eighty seven percent of patients were satisfied and pretreatment activities were completely regained in 78.3% of patients. Disk height at the indicator and adjacent levels and ROM at the indicator segment and the entire lumbar spine were preserved. No loosening of implants was observed. Explantation of FJR and subsequent fusion had to be performed in four cases (15.4%)., Conclusions:  In selected cases, long-term results of FJR show good outcome concerning pain, quality of life, preservation of lumbar spine motion, and protection of adjacent level., Competing Interests: None declared., (Thieme. All rights reserved.)

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. High infiltration rates and poor therapy responses make it the deadliest glioma. The tumor metabolism is known to differ from normal one and is influenced through various factors which can lead to longer survival. Metabolites are small molecules (< 1500 Da) that display the metabolic pathways in the tissue. To determine the metabolic alterations between tumor and peritumoral tissue in human GBMs, mass spectrometry imaging (MSI) was performed on thin sections from 25 resected tumors. In addition, the GBMs were compared with six gliomas harboring a mutation in the isocitrate dehydrogenase (IDH1) gene (IDH1). With this technique, a manifold of analytes can be easily visualized on a single tissue section. Metabolites were annotated based on their accurate mass using high resolution MSI. Differences in their mean intensities in the tumor and peritumoral areas were statistically evaluated and abundances were visualized on the tissue. Enhanced levels of the antioxidants ascorbic acid, taurine, and glutathione in tumor areas suggest protective effects on the tumor. Increased levels of purine and pyrimidine metabolism compounds in GBM areas indicate the high energy demand. In accordance with these results, enhanced abundances of lactate and glutamine were detected. Moreover, decreased abundance of N-acetylaspartate, a marker for neuronal health, was measured in tumor areas. Obtained metabolic information could potentially support and personalize therapeutic approaches, hence emphasizing the suitability of MSI for GBM research., (© 2020 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Neuropathology.)

Context: Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging., Objective: We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness., Design and Subjects: Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients., Results: Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated., Conclusion: We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: If biochemical control of acromegaly is not achieved by operation and medication, radiotherapy may be indicated., Objective: To describe fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) regarding excess of IGF-1 and pituitary function., Design and Methods: A retrospective analysis of 352 patients (4126 patient-years) from the German Acromegaly Registry was performed. Follow-up was 1.0-45.1 years after radiotherapy. Therapeutic success was defined by low or normal IGF-1 according to center-specific reference ranges without (= remission) or on (= controlled disease) suppressive medication., Results: Time between radiotherapy and last follow-up was 13.0 ± 8.2 years for FRT (n = 233) and 8.9 ± 5.0 years for SRS (n = 119, P < 0.001). Median (IQR) basal growth hormone before radiotherapy was 6.3 (2.9-16.2) ng/mL for FRT and 3.5 (1.8-6.9) ng/mL for SRS (P < 0.001). Mean time in uncontrolled state was 3.0 years after FRT and 2.1 years after SRS (95% CI for the difference is 0.1 to 1.6 years, P = 0.021). The 10-year calculated remission rate was 48% for FRT and 52% for SRS (95% CI for the difference is -18 to 26% age points, P = 0.74) and the respective controlled disease rate was 23 and 26%. The odds ratio for adrenocorticotropic or thyreotropic insufficiency was 0.54 (95% CI: 0.30-1.00, P = 0.049) in SRS compared to FRT patients., Conclusion: Both after FRT and SRS about 75% of patients with acromegaly are in remission or controlled after 10 years. A slightly faster achievement of target values was observed after SRS. The rate of pituitary insufficiency in FRT patients is significantly higher.

Importance: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established., Objective: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH., Design, Setting, and Participants: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015)., Exposure: Surgical hematoma evacuation vs conservative treatment., Main Outcomes and Measures: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH., Results: Among 578 patients with cerebellar ICH, propensity score-matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm3 vs 18.8 cm3). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], -3.7% [95% CI, -8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm3 was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm3, 30.6% vs 62.3% [P = .003]; ARD, -34.7% [-38.8% to -30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm3, 74.5% vs 45.1% [P < .001]; ARD, 28.2% [95% CI, 24.6% to 31.8%]; P value for interaction, .02)., Conclusions and Relevance: Among patients with cerebellar ICH, surgical hematoma evacuation, compared with conservative treatment, was not associated with improved functional outcome. Given the null primary outcome, investigation is necessary to establish whether there are differing associations based on hematoma volume.

Objective: To determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH., Methods: Retrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC., Results: IHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04-1.93) vs non-LDSH: 1.32 (0.33-3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38-4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4-6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume <4.4 mL: 0.18 (0.04-0.78); p=0.022) and low National Institutes of Health Stroke Scale (NIHSS) score on admission (OR: NIHSS <4: 0.29 (0.11-0.78); p=0.014) were significantly associated with fewer IHC., Conclusions: Heparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention., Competing Interests: Competing interests: JBK reports grants from Covidien (Medtronic), personal fees from Bayer, Pfizer and Sanofi. ME reports grants and other from Bayer, other from Boehringer Ingelheim, BMS/Pfizer and Daiichi Sankyo during the conduct of the study; grants from DFG, BMBF, EU, Corona Foundation and Fondation Leducq, other from Amgen, GSK, Novartis, Sanofi and Covidien. KGH reports grants and personal fees from Bayer, personal fees from Daiichi Sankyo, BMS, Pfizer, Boehringer Ingelheim, Sanofi-Aventis and Edwards Lifesciences, non-financial support from Getemed, personal fees from EIP Pharma and Medtronic. JS reports personal fees from Bayer, Pfizer/BMS, Daiichi and Boehringer Ingelheim. PAR reports personal fees from Boehringer Ingelheim, Bayer, Daiichi Sankyo and Pfizer. JCP reports personal fees from Boehringer Ingelheim and Pfizer. TR reports personal fees from BMS Pfizer, Bayer Healthcare, Daiichi Sankyo and Boehringer Ingelheim. JV reports grants from Medtronic and Boston Scientific and fees from Medtronic, St Jude, Boston Scientific, UCB, Merz, Allergan, Teva, Novartis and AbbVie. WM reports personal fees from Boehringer Ingelheim and Bayer Pharma. PK reports personal fees from Bayer, Boehringer Ingelheim, Daiichi Sankyo and Pfizer/Bristol-Myers Squibb. FE reports grants and personal fees from Boehringer Ingelheim, personal fees from Bayer Pharma, Pfizer Pharma, Bristol-Myers Squibb and Daiichi Sankyo. MN reports personal fees from Speaker’s fee Pfizer/BMS and Boehringer Ingelheim. PDS reports personal fees from Boehringer Ingelheim, Bayer, BMS/Pfizer, Daiichi and Medtronic. JG reports personal fees from Pfizer. UJK reports other from Daiichi Sankyo and Bayer. GRF reports personal fees from Bayer and Boehringer. CD reports speaking fees from Bayer, UCB, Daiichi Sankyo and Pfizer. JM reports personal fees from Boehringer Ingelheim and Bayer Healthcare. HN reports personal fees from Boehringer Ingelheim and Daiichi. JR reports personal fees from Bayer, Boehringer, Pfizer and Bristol Myers Squibb. MS reports grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and the European Union (EU) and fees from Bristol-Myers Squibb, GlaxoSmithKline, Merz Pharmaceuticals, Novartis Pharma, Orion Pharma, Pharmacia, Roche, Sanofi, Teva Pharma and UCB Pharma. GR reports personal fees from Boehringer Ingelheim, Pfizer and Bayer, grants from Daiichi. HB reports personal fees from Honoraria for lectures from Bayer Vital, Boehringer Ingelheim, Bristol-Myers Squibb and Daiichi Sankyo. HS reports grants from Bayer Healthcare. FP reports personal fees from Pfizer/BMS, Bayer, Boehringer Ingelheim and Daiichi Sankyo. JCW reports personal fees from Boehringer Ingelheim Pharma GmbH & Co. KGH reports personal fees from Daiichi Sankyo Pharma. AG reports personal fees from Daiichi Sankyo, Bayer, Boehringer Ingelheim and Bristol-Myers Squibb/Pfizer. GFH reports participation in the Respect-ESUS trial. SS reports personal fees from Boehringer Ingelheim and grants from Daiichi. HBH reports personal fees from Boehringer Ingelheim, Daiichi Sankyo and Novartis, grants from Medtronic., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)