18F-fluoro-ethyl-tyrosine PET co-registered with MRI in patients with persisting acromegaly.

OBJECTIVE: To report our experience with 18F-fluoro-ethyl-tyrosine (FET) positron emission tomography-computed tomography (PET-CT) co-registered with magnetic resonance imaging (MRI) (FET-PET/MRICR) in the care trajectory for persistent acromegaly. DESIGN: Prospective case series. PATIENTS: Ten patients with insufficiently controlled acromegaly referred to our team to evaluate surgical options. MEASUREMENTS: FET-PET/MRICR was used to support decision-making if MRI alone and multidisciplinary team evaluation did not provide sufficient clarity to proceed to surgery. RESULTS: FET-PET/MRICR showed suspicious (para)sellar tracer uptake in all patients. In five patients FET-PET/MRICR was fully concordant with conventional MRI, and in one patient partially concordant. FET-PET/MRICR identified suggestive new foci in four other patients. Surgical re-exploration was performed in nine patients (aimed at total resection (6), debulking (2), diagnosis (1)), and one patient underwent radiation therapy. In 7 of 9 (78%) operated patients FET-PET/MRICR findings were confirmed intraoperatively, and in six (67%) also histologically. IGF-1 decreased significantly in eight patients (89%). All patients showed clinical improvement. Complete biochemical remission was achieved in three patients (50% of procedures in which total resection was anticipated feasible). Biochemistry improved in five and was unchanged in one patient. No permanent complications occurred. At six months, optimal outcome (preoperative intended goal achieved without permanent complications) was achieved in six (67%) patients and an intermediate outcome (goal not achieved, but no complications) in the other three patients. CONCLUSIONS: In patients with persisting acromegaly without a clear surgical target on MRI, FET-PET/MRICR is a new tracer to provide additional information to aid decision-making by the multidisciplinary pituitary team.

Efficacy and Safety of Endoscopic Transsphenoidal Resection for Prolactinoma: A Retrospective Multicenter Case-series.

BACKGROUND: Endoscopic transsphenoidal surgery (ETSS) for prolactinoma is reserved for dopamine agonist (DA) resistance, intolerance, or apoplexy. High remission (overall 67%, microprolactinoma up to 90%), low recurrence (5-20%) rates highlighted that surgery might be first-line treatment. AIMS: To report on outcomes of ETSS in a cohort of prolactinomas. METHODS: Multicenter retrospective cohort of 137 prolactinoma patients (age 38.2 ± 13.7 years; 61.3% female, median follow-up 28.0 [15.0-55.5] months) operated between 2010-2019 with histopathological confirmation. RESULTS: Median preoperative prolactin levels were 166 (98-837 µg/L; males 996 [159-2145 µg/L] vs. females 129 [84-223 µg/L], p <0.001). 56 (40.9%) microprolactinomas, 69 (50.4%) macroprolactinomas, and 7 (5.1%) giant prolactinomas were included, whereas no adenoma was detected in 5 (3.6%) patients. Males had larger tumors (macroprolactinomas: 38, 71.7%) vs. 31 (36.9%), p <0.001; giant prolactinomas: 7 (13.2%) vs. 0 (0.0%), (p <0.001). Prolactinomas were graded as KNOSP-3 in 15 (11.5%), and KNOSP-4 in 20 (15.3%) patients. Primary indication was DA intolerance (59, 43.1%); males 14 (26.4%) vs. females 45 (53.6%), p = 0.006. Long-term remission (i.e., DA-free prolactin level <1xULN) was achieved in 87 (63.5%) patients, being higher in intended complete resection (69/92 [75.0%]), and lower in males (25 [47.2%] vs. 62 females [73.8%], p = 0.002). Transient DI (n = 29, 21.2%) was the most frequent complication. CONCLUSIONS: Despite high proportions of macroprolactinoma and KNOSP 3-4, long-term remission rates were 63.5% overall, and 83.3% in microprolactinoma patients. Males had less favorable remission rate compared to females. These findings highlight that ETSS may be a safe and efficacious treatment to manage prolactinoma.

Neuropsychiatric adverse effects of synthetic glucocorticoids: A systematic review and meta-analysis.

BACKGROUND: Synthetic glucocorticoids are widely used among patients suffering from a wide range of diseases. Glucocorticoids are very efficacious, but can be accompanied by neuropsychiatric adverse effects. This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids. METHODS: Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and non-users were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model. RESULTS: We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95%CI 14%-33%), 11% for mania (95%CI 2%-46%), 8% for anxiety (95%CI 2%-25%), 16% for delirium (95%CI 6%-36%), and 52% for behavioural changes (95%CI 42%-61%). Questionnaire scores for depression (SMD of 0.80 (95%CI 0.35-1.26)), and mania (0.78 (95%CI 0.14-1.42)) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use. CONCLUSIONS: The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.

Prospective Integrated Individualized Clinical Decision-making and Outcome Evaluation for Surgery in Patients with Acromegaly: A New Paradigm?

BACKGROUND: Growth-hormone-producing pituitary adenomas have variable likelihood for biochemical remission (BR). During preoperative counseling, individual estimated surgical likelihoods/risks should be balanced against alternative (medical) treatments, which is necessary for accurate outcome presentation. Preoperative estimation of BR or total resection (TR) likelihoods have not been reported, resulting in extrapolation of individual outcomes. AIMS: To share an innovative outcome reporting paradigm by integrating surgical decision-making, and expected/realized results, resulting from the Value-Based Health Care (VBHC) care path with periodical performance evaluation and care innovation cycle. METHODS: Prospective cohort study of consecutive patients with acromegaly undergoing surgery (January 2016-December 2020; postoperative follow-up ≥6 months) reporting on both classic, and novel innovative outcome evaluations. RESULTS: Fifty eight patients (66 procedures) were included. Intended TR was achieved in 34/50 procedures, whereas intended debulking was achieved in 15/16 procedures. 38/66 procedures resulted in BR, and 4 procedures resulted in permanent complications. Achieving intended surgical goal was estimated preoperatively as likely in 33 (goal achieved (GA) in 28/33), potentially in 27 (GA in 19/27), and unlikely in 6 procedures (GA in 2/6). Integrated Outcome Square 1 (IOQ1) -intended effect achieved without complications- was achieved in 46/66 patients. CONCLUSION: Implementation of the developed quality process positively affects preoperative individual shared decision-making, resulting in improved (individual) outcomes, particularly in complex patients for whom preoperative chances are not fully reflected by tumor size and KNOSP grade, e.g., reoperations, or other challenging circumstances identified during preoperative counseling. Through repeated evaluations, our own team's knowledge increased, allowing for improved individualized treatment strategies.

Recovery of Third, Fourth, and Sixth Cranial Nerve Palsies in Pituitary Adenoma and Meningioma Patients.

BACKGROUND: This retrospective, observational cohort study aimed to determine recovery rate and recovery time of ocular motor nerve palsies (OMP) of third (CN III), fourth (CN IV), or sixth cranial nerves (CN VI)-and associated prognostic factors-in meningioma and pituitary adenoma (PA) patients. METHODS: A total of 25 meningioma (28 eyes) and 33 PA patients (36 eyes), treated at the Leiden University Medical Center in the Netherlands from January 1, 1978 to January 31, 2021, were included. OMPs were evaluated according to a newly created recovery scale using on-clinical and orthoptic examinations, which were performed every 3-4 months until palsy recovery, or at 18 months follow-up. RESULTS: Recovery rates of CN III (meningioma 23.5% vs PA 92.3%), CN IV (meningioma 20% vs PA 100%), and CN VI (meningioma 60% vs PA 100%) palsies were observed at 18 months follow-up, with differences between the 2 tumor types being observed in the treated patients only. Median recovery time of all OMPs combined was significantly longer in meningioma patients (37.9 ± 14.3 months vs 3.3 ± 0.1 months; P < 0.001). No significant protective or risk factors for recovery rate or time were identified. CONCLUSIONS: OMP recovery rates in treated patients were more favorable in patients with PA compared with patients with meningiomas, independent of OMP cause. With these new insights in OMP recovery, more accurate prognoses and appropriate follow-up strategies can be determined for meningioma and PA patients with OMPs.

Care trajectories of surgically treated patients with a prolactinoma: why did they opt for surgery?

PURPOSE: To describe care trajectories in patients with prolactinoma, aiming to clarify the rationale for surgery. METHODS: Retrospective observational cohort study of consecutive patients with prolactinoma undergoing surgery from 2017 to 2019 at the referral center (RC), prior to surgery being considered a viable treatment option (i.e. PRolaCT study). Demographics and clinical data (type and duration of pretreatment and surgical indications, goals, and outcomes) were collected from patient records. Care trajectories were divided into three phases: (1) diagnosis and initial treatment, (2) endocrine treatment at the RC, and (3) surgical treatment. RESULTS: 40 patients were included (31 females (77.5%), median age 26.5 (14-63) years. Indications for surgery were dopamine agonist (DA) intolerance (n = 31, 77.5%), resistance (n = 6, 15.0%), and patient/physician preference (n = 3, 7.5%). Patients were pretreated with DA (n = 39 (97.5%)), and surgery (n = 3 (7.5%)). Median disease duration at surgery was 4 (0-27) years. Primary surgical goal was total resection in 38 patients (95.0%), of which biochemical remission was achieved 6 months postoperatively in 23 patients (62.2%), and clinical remission in 6 patients (16.2%), missing data n = 1. CONCLUSION: Care trajectories were highly individualized based on patient and tumor characteristics, as well as the multidisciplinary team's assessment (need for alternative treatment, surgical chances and risks). Most patients were pretreated pharmacologically and had broad variation in timing of referral, undergoing surgery as last-resort treatment predominantly due to DA intolerance. High quality imaging and multidisciplinary consultations with experienced neurosurgeons and endocrinologists enabling treatment tailored to patients' needs were prerequisites for adequate counseling in treatment of patients with prolactinoma.

The prevalence and severity of fatigue in meningioma patients and its association with patient-, tumor- and treatment-related factors.

Background: Fatigue is a commonly reported and severe symptom in primary brain tumor patients, but the exact occurrence in meningioma patients is unknown. This study aimed to determine the frequency and severity of fatigue in meningioma patients as well as associations between the level of fatigue and patient-, tumor-, and treatment-related factors. Methods: In this multicenter cross-sectional study, meningioma patients completed questionnaires on fatigue (MFI-20), sleep (PSQI), anxiety and depression (HADS), tumor-related symptoms (MDASI-BT), and cognitive functioning (MOS-CFS). Multivariable regression models were used to evaluate the independent association between fatigue and each patient-, tumor-, and treatment-related factor separately, corrected for relevant confounders. Results: Based on predetermined in- and exclusion criteria, 275 patients, on average 5.3 (SD = 2.0) year since diagnosis, were recruited. Most patients had undergone resection (92%). Meningioma patients reported higher scores on all fatigue subscales compared to normative data and 26% were classified as fatigued. Having experienced a complication due to resection (OR 3.6, 95% CI: 1.8-7.0), having received radiotherapy (OR 2.4, 95% CI: 1.2-4.8), a higher number of comorbidities (OR 1.6, 95% CI: 1.3-1.9) and lower educational level (low level as reference; high level OR 0.3, 95% CI: 0.2-0.7) were independently associated with more fatigue. Conclusions: Fatigue is a frequent problem in meningioma patients even many years after treatment. Both patient- and treatment-related factors were determinants of fatigue, with the treatment-related factors being the most likely target for intervention in this patient population.

Patient perspectives on indwelling urinary catheters and fluid balances after transsphenoidal pituitary surgery: a qualitative study.

OBJECTIVES: To explore the perceptions and experiences of patients who underwent transsphenoidal pituitary gland and (para)sellar tumour surgery regarding indwelling urinary catheters (IDUCs) and the postoperative fluid balance. DESIGN: Qualitative study using semistructured interviews based on the attitudes, social influence and self-efficacy model and expert knowledge. PARTICIPANTS: Twelve patients who underwent transsphenoidal pituitary gland tumour surgery and received an IDUC during or after surgery. SETTING: One patient was interviewed in the endocrinology outpatient clinic and 11 patients were interviewed on the neurosurgery ward. RESULTS: Five major themes emerged: (1) conflicting information and preoperative expectations, (2) IDUCs perceived as patient-friendly during bedrest, particularly for women, (3) little room for patients' opinions, (4) physical and emotional limitations and (5) fluid balance causes confusion. Information regarding IDUC placement and fluid balance given to patients both preoperatively and postoperatively did not meet their expectations, which led to confusion and uncertainty. The IDUC was perceived as preferable if bedrest was mandatory, preferred particularly by women. Patient could not mobilise freely due to the IDUC and felt ashamed, judged by others and dependent on nurses. CONCLUSIONS: This study provides insight into the challenges patients experience in relation to the IDUC and fluid balance. Perceptions on the necessity of an IDUC varied among patients and were influenced by both physical and emotional impediments. A clear, frequent and daily communication between healthcare professionals and patients to evaluate IDUC and fluid balance use is necessary to increase patient satisfaction.

Healthcare utilization and costs among intracranial meningioma patients during long-term follow-up.

PURPOSE: Few studies have reported on healthcare utilization and costs for intracranial meningioma patients, while the tumor and its treatment profoundly affect patients' functioning and well-being. Here we evaluated healthcare utilization and costs, including their determinants. METHODS: A multicenter cross-sectional study of adult meningioma patients ≥ 5 years after intervention. Patients completed three validated patient-reported outcome measures (PROMs) assessing patients 'functioning and wellbeing (SF-36, EORTC QLQ-BN20, and HADS) and a study-specific questionnaire assessing healthcare utilization over the previous twelve months. Healthcare costs of the twelve months prior were calculated using reported healthcare utilization ≥ 5 years after intervention by the Dutch Manual for Economic Evaluation in Healthcare. Determinants for healthcare utilization and costs were determined with regression analyses. RESULTS: We included 190 patients with WHO grade I or II meningioma after a mean follow-up since intervention of 9.2 years (SD 4.0). The general practitioner (80.5%), physiotherapist (37.9%), and neurologist (25.4%) were visited most often by patients. Median annual healthcare costs were €871 (IQR €262-€1933). Main contributors to these costs were medication (45.8% of total costs, of which anti-seizure medication was utilized most [21.6%]), specialist care (17.7%), and physiotherapy (15.5%). Lower HRQoL was a significant determinant for higher healthcare utilization and costs. CONCLUSION: In patients with meningioma, medication costs constituted the largest expenditure of total healthcare costs, in particular anti-seizure medication. Particularly a lower HRQoL was a determinant for healthcare utilization and costs. A patient-specific approach aimed at improving patients' HRQoL and needs could be beneficial in reducing disease burden and functional recovery.

Unexpected concomitant pituitary adenoma and suprasellar meningioma: a case report and review of the literature.

We report a case of a 75-year-old patient with hypopituitarism, bitemporal visual field deficits and a parasellar mass on pituitary MRI. During surgery, suspicion was raised that a non-functioning pituitary adenoma was accompanied by an abutting diaphragm sellae meningioma, which was confirmed at pathological examination. In retrospect, the initial MRI suggested two separate tumours on the basis of differing densities but this distinction was not seen on the last preoperative MRI.

Impact of early postoperative indwelling urinary catheter removal: A systematic review.

BACKGROUND: Indwelling urinary catheters (IDUCs) are associated with complications and early removal is therefore essential. Currently, it is unknown what the effect of a specific removal time is and what the consequences of this removal time are. RESEARCH QUESTION: To present an overview of the available evidence to determine the effects of three postoperative IDUC removal times (after a certain number of hours, at a specific time of day and flexible removal time) on the development of complications in hospital. METHODS: PubMed, Medline, Embase, Emcare and Cochrane Central Register of Controlled Trials were searched till 6 June, 2021. Studies were included that described the effect of the removal time in relation to re-catheterisation, urinary tract infections (UTIs), ambulation time, time of first voiding and hospital stay. The quality of the studies was assessed with the Newcastle-Ottawa Scale and the Cochrane Effective Practice and Organisation of Care. A narrative descriptive analysis was performed. PRISMA guidelines were followed in reporting this review. RESULTS: Twenty studies were included from which 18 compared removal after a number of hours, 1 reported on a specific removal time and 1 reported on both topics. The results were contradicting regarding the hypothesis that later removal increases the incidence of UTIs. Earlier removal does not lead to a higher re-catheterisation rate while immediate removal is beneficial for reducing the time to first ambulation and shortening the hospital stay. Studies reporting on specific removal times did not find differences in outcomes. No study addressed flexible removal time. CONCLUSIONS: There is inconclusive evidence that earlier removal results in less UTIs, despite the incidence of UTIs increasing if the IDUC is removed ≥24 h. Immediate or after 1-2 day(s) removal does not lead to higher re-catheterisation rates while immediate removal results in earlier ambulation and shorter length of hospital stay. IMPLICATIONS OF KEY FINDINGS: Nurses should focus on early IDUC removal while being aware of urinary retention.

Starting point for benchmarking outcomes and reporting of pituitary adenoma surgery within the European Reference Network on Rare Endocrine Conditions (Endo-ERN): results from a meta-analysis and survey study.

Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN) aims to organize high-quality healthcare throughout Europe, including care for pituitary adenoma patients. As surgery is the mainstay of treatment, we aimed to describe the current surgical practice and published surgical outcomes of pituitary adenoma within Endo-ERN. Design and Methods: Systematic review and meta-analysis of studies reporting surgical outcomes of pituitary adenoma patients within Endo-ERN MTG6 pituitary reference centers between 2010 and 2019. A survey was completed by reference centers on their current surgical practice. Results: A total of 18 out of 43 (42%) reference centers located in 7 of the 20 (35%) MTG6-represented countries published 48 articles. Remission rates were 50% (95% CI: 42-59) for patients with acromegaly, 68% (95% CI: 60-75) for Cushing's disease, and 53% (95% CI: 39-66%) for prolactinoma. Gross total resection was achieved in 49% (95% CI: 37-61%) of patients and visual improvement in 78% (95% CI: 68-87). Mortality, hemorrhage, and carotid injury occurred in less than 1% of patients. New-onset hypopituitarism occurred in 16% (95% CI: 11-23), transient diabetes insipidus in 12% (95% CI: 6-21), permanent diabetes insipidus in 4% (95% CI: 3-6), syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in 9% (95% CI: 5-14), severe epistaxis in 2% (95% CI: 0-4), and cerebrospinal fluid leak in 4% (95% CI: 2-6). Thirty-five (81%) centers completed the survey: 54% were operated endoscopically and 57% were together with an ENT surgeon. Conclusion: The results of this study could be used as a first benchmark for the outcomes of pituitary adenoma surgery within Endo-ERN. However, the heterogeneity between studies in the reporting of outcomes hampers comparability and warrants outcome collection through registries.

Endoscopic-assisted transorbital surgery: Where do we stand on the scott's parabola? personal considerations after a 10-year experience.

Transorbital approaches are genuinely versatile surgical routes which show interesting potentials in skull base surgery. Given their "new" trajectory, they can be a very useful adjunct to traditional routes, even being a valid alternative to them in some cases, and add valuable opportunities in selected patients. Indications are constantly expanding, and currently include selected intraorbital, skull base and even intra-axial lesions, both benign and malignant. Given their relatively recent development and thus unfamiliarity among the skull base community, achieving adequate proficiency needs not only a personalized training and knowledge but also, above all, an adequate case volume and a dedicated setting. Current, but mostly future, applications should be selected by genetic, omics and biological features and applied in the context of a truly multidisciplinary environment.

Costs and Its Determinants in Pituitary Tumour Surgery.

Purpose: Value-based healthcare (VBHC) provides a framework to improve care by improving patient outcomes and reducing healthcare costs. To support value-based decision making in clinical practice we evaluated healthcare costs and cost drivers in perioperative care for pituitary tumour patients. Methods: We retrospectively assessed financial and clinical data for surgical treatment up to the first year after surgery of pituitary tumour patients treated between 2015 and 2018 in a Dutch tertiary referral centre. Multivariable regression analyses were performed to identify determinants of higher costs. Results: 271 patients who underwent surgery were included. Mean total costs (SD) were €16339 (13573) per patient, with the following cost determinants: surgery time (€62 per minute; 95% CI: 50, 74), length of stay (€1331 per day; 95% CI 1139, 1523), admission to higher care unit (€12154 in total; 95% CI 6413, 17895), emergency surgery (€10363 higher than elective surgery; 95% CI: 1422, 19305) and postoperative cerebrospinal fluid leak (€14232; 95% CI 9667, 18797). Intradural (€7128; 95% CI 10421, 23836) and combined transsphenoidal/transcranial surgery (B: 38494; 95% CI 29191, 47797) were associated with higher costs than standard. Further, higher costs were found in these baseline conditions: Rathke's cleft cyst (€9201 higher than non-functioning adenoma; 95% CI 1173, 17230), giant adenoma (€19106 higher than microadenoma; 95% CI 12336, 25877), third ventricle invasion (€14613; 95% CI 7613, 21613) and dependent functional status (€12231; 95% CI 3985, 20477). In patients with uncomplicated course, costs were €8879 (3210) and with complications €17551 (14250). Conclusions: Length of hospital stay, and complications are the main drivers of costs in perioperative pituitary tumour healthcare as were some baseline features, e.g. larger tumors, cysts and dependent functional status. Costs analysis may correspond with healthcare resource utilization and guide further individualized care path development and capacity planning.

Implementation of functional imaging using 11C-methionine PET-CT co-registered with MRI for advanced surgical planning and decision making in prolactinoma surgery.

PURPOSE: To report the first experience of our multidisciplinary team with functional imaging using 11C-methionine positron emission tomography-computed tomography (11C-methionine PET-CT) co-registered with MRI (Met-PET/MRICR) in clinical decision making and surgical planning of patients with difficult to treat prolactinoma. METHODS: In eighteen patients with prolactinoma, referred to our tertiary referral centre because of intolerance or resistance for dopamine agonists (DA), Met-PET/MRICR was used to aid decision-making regarding therapy. RESULTS: Met-PET/MRICR was positive in 94% of the patients. MRI and Met-PET/MRICR findings were completely concordant in five patients, partially concordant in nine patients, and non-concordant in four patients. In five patients Met-PET/MRICR identified lesion(s) that were retrospectively also visible on MRI. Met-PET/MRICR was false negative in one patient, with a cystic adenoma on conventional MRI. Thirteen patients underwent transsphenoidal surgery, with nine achieving full biochemical remission, two clinical improvement and near normalized prolactin levels, and one patient clinical improvement with significant tumour reduction. Hence, nearly all patients (94%) were considered to have a positive outcome. Permanent complication rate was low. Three patients continued DA, two patients have a wait and scan policy. CONCLUSION: Met-PET/MRICR can provide additional information to guide multidisciplinary preoperative and intraoperative decision making in selected cases of prolactinoma. This approach resulted in a high remission rate with a low rate of complications in our expert centre.

Impact of patient-reported nasal symptoms on quality of life after endoscopic pituitary surgery: a prospective cohort study.

PURPOSE: Endoscopic transsphenoidal surgery causes nasal morbidity and negatively affects health-related quality of life (HRQoL). Knowledge on actionable symptoms that could improve postoperative HRQoL is therefore important. This study assessed the impact of nasal symptoms on postoperative HRQoL. METHODS: This perioperative cohort study included 103 adult patients undergoing endoscopic pituitary adenoma resection (August 2016-December 2018), with measurements preoperatively, and 5 days, 6 weeks and 6 months after surgery. Nasal symptoms were measured with the Anterior Skull base nasal inventory-12, and HRQoL with the Short Form-36 (SF-36) physical (PCS) and mental component scores (MCS). Linear regression analysis was used to assess (1) determinants of postoperative nasal morbidity, (2) associations between number of symptoms or (3) individual symptoms and HRQoL, and (4) the percentage of variance of HRQoL explained by nasal symptoms. RESULTS: The number of nasal symptoms transiently increased after surgery. No significant treatment- or disease-related determinants of nasal morbidity were identified. The number of nasal symptoms was significantly associated with a lower PCS (ß = - 1.0; 95%CI - 1.5, - 0.4), but not with MCS at 6 weeks. Similar results were observed at 6 months. Headaches (42.2%), problems with smell (42.0%), and taste (36.0%) were the most prevalent symptoms, while sense of smell and taste, and nasal discharge showed the strongest associations with HRQoL. CONCLUSIONS: Postoperative nasal symptoms, in particular problems with smell and taste, significantly affect pituitary patients' physical HRQoL. Monitoring of these symptoms may aid in determining which patients may benefit from intensified follow-up and treatment, aiming to optimize HRQoL.

Long-term health-related quality of life and neurocognitive functioning after treatment in skull base meningioma patients.

OBJECTIVE: Patients with skull base meningioma (SBM) often require complex surgery around critical neurovascular structures, placing them at high risk of poor health-related quality of life (HRQOL) and possibly neurocognitive dysfunction. As the survival of meningioma patients is near normal, long-term neurocognitive and HRQOL outcomes are important to evaluate, including evaluation of the impact of specific tumor location and treatment modalities on these outcomes. METHODS: In this multicenter cross-sectional study including patients 5 years or more after their last tumor intervention, Short-Form Health Survey (SF-36) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-BN20 questionnaires were used to assess generic and disease-specific HRQOL. Neurocognitive functioning was assessed with standardized neuropsychological assessment. SBM patient assessments were compared with those of 1) informal caregivers of SBM patients who served as controls and 2) convexity meningioma patients. In addition, the authors compared anterior/middle SBM patients with posterior SBM patients and anterior/middle and posterior SBM patients separately with controls. Multivariable and propensity score regression analyses were performed to correct for possible confounders. RESULTS: Patients with SBM (n = 89) with a median follow-up of 9 years after the last intervention did not significantly differ from controls (n = 65) or convexity meningioma patients (n = 84) on generic HRQOL assessment. Statistically significantly but not clinically relevantly better disease-specific HRQOL was found for SBM patients compared with convexity meningioma patients. Anterior/middle SBM patients (n = 62) had significantly and clinically relevantly better HRQOL in SF-36 and EORTC QLQ-BN20 scores than posterior SBM patients (n = 27): physical role functioning (corrected difference 17.1, 95% CI 0.2-34.0), motor dysfunction (-10.1, 95% CI -17.5 to -2.7), communication deficit (-14.2, 95% CI -22.7 to -5.6), and weakness in both legs (-10.1, 95% CI -18.8 to -1.5). SBM patients whose primary treatment was radiotherapy had lower HRQOL scores compared with SBM patients who underwent surgery on two domains: bodily pain (-33.0, 95% CI -55.2 to -10.9) and vitality (-18.9. 95% CI -33.7 to -4.1). Tumor location and treatment modality did not result in significant differences in neurocognitive functioning, although 44% of SBM patients had deficits in at least one domain. CONCLUSIONS: In the long term, SBM patients do not experience significantly more sequelae in HRQOL and neurocognitive functioning than do controls or patients with convexity meningioma. Patients with posterior SBM had poorer HRQOL than anterior/middle SBM patients, and primary treatment with radiotherapy was associated with worse HRQOL. Neurocognitive functioning was not affected by tumor location or treatment modality.

State of the Art of Patient-reported Outcomes in Acromegaly or GH Deficiency: A Systematic Review and Meta-analysis.

CONTEXT: Insight into the current landscape of patient-reported outcome (PRO) measures (PROM) and differences between PROs and conventional biochemical outcomes is pivotal for future implementation of PROs in research and clinical practice. Therefore, in studies among patients with acromegaly and growth hormone deficiency (GHD), we evaluated (1) used PROMs, (2) their validity, (3) quality of PRO reporting, (4) agreement between PROs and biochemical outcomes, and (5) determinants of discrepancies. EVIDENCE ACQUISITION: We searched 8 electronic databases for prospective studies describing both PROs and biochemical outcomes in acromegaly and GHD patients. Quality of PRO reporting was assessed using the International Society for Quality of Life Research (ISOQOL) criteria. Logistic regression analysis was used to evaluate determinants. EVIDENCE SYNTHESIS: Ninety studies were included (acromegaly: n = 53; GHD: n = 37). Besides nonvalidated symptom lists (used in 37% of studies), 36 formal PROMs were used [predominantly Acromegaly Quality of Life Questionnaire in acromegaly (43%) and Quality of Life-Assessment of Growth Hormone Deficiency in Adults in GHD (43%)]. Reporting of PROs was poor, with a median of 37% to 47% of ISOQOL items being reported per study. Eighteen (34%) acromegaly studies and 12 (32%) GHD studies reported discrepancies between PROs and biochemical outcomes, most often improvement in biochemical outcomes without change in PROs. CONCLUSIONS: Prospective studies among patients with acromegaly and GHD use a multitude of PROMs, often poorly reported. Since a substantial proportion of studies report discrepancies between PROs and biochemical outcomes, PROMs are pivotal in the evaluation of disease activity. Therefore, harmonization of PROs in clinical practice and research by development of core outcome sets is an important unmet need.