Reported outcomes in transsphenoidal surgery for pituitary adenomas: a systematic review

PURPOSE: Transsphenoidal surgery is an established treatment for pituitary adenomas. We examined outcomes and time points following transsphenoidal surgery for pituitary adenoma to identify reporting heterogeneity within the literature. METHODS: A systematic review of studies that reported outcomes for transsphenoidal surgery for pituitary adenoma 1990–2021 were examined. The protocol was registered a priori and adhered to the PRISMA statement. Studies in English with > 10 patients (prospective) or > 500 patients (retrospective) were included. RESULTS: 178 studies comprising 427,659 patients were included. 91 studies reported 2 or more adenoma pathologies within the same study; 53 studies reported a single pathology. The most common adenomas reported were growth hormone-secreting (n = 106), non-functioning (n = 101), and ACTH-secreting (n = 95); 27 studies did not state a pathology. Surgical complications were the most reported outcome (n = 116, 65%). Other domains included endocrine (n = 104, 58%), extent of resection (n = 81, 46%), ophthalmic (n = 66, 37%), recurrence (n = 49, 28%), quality of life (n = 25, 19%); and nasal (n = 18, 10%). Defined follow up time points were most reported for endocrine (n = 56, 31%), extent of resection (n = 39, 22%), and recurrence (n = 28, 17%). There was heterogeneity in the follow up reported for all outcomes at different time points: discharge (n = 9),  1 year (n = 69). CONCLUSION: Outcomes and follow up reported for transsphenoidal surgical resection of pituitary adenoma are heterogenous over the last 30 years. This study highlights the necessity to develop a robust, consensus-based, minimum, core outcome set. The next step is to develop a Delphi survey of essential outcomes, followed by a consensus meeting of interdisciplinary experts. Patient representatives should also be included. An agreed core outcome set will enable homogeneous reporting and meaningful research synthesis, ultimately improving patient care

Reported baseline variables in transsphenoidal surgery for pituitary adenoma over a 30 year period: a systematic review

Purpose: Heterogeneous reporting in baseline variables in patients undergoing transsphenoidal resection of pituitary adenoma precludes meaningful meta-analysis. We therefore examined trends in reported baseline variables, and degree of heterogeneity of reported variables in 30 years of literature. Methods: A systematic review of PubMed and Embase was conducted on studies that reported outcomes for transsphenoidal surgery for pituitary adenoma 1990–2021. The protocol was registered a priori and adhered to the PRISMA statement. Full-text studies in English with > 10 patients (prospective), > 500 patients (retrospective), or randomised trials were included. Results: 178 studies were included, comprising 427,659 patients: 52 retrospective (29%); 118 prospective (66%); 9 randomised controlled trials (5%). The majority of studies were published in the last 10 years (71%) and originated from North America (38%). Most studies described patient demographics, such as age (165 studies, 93%) and sex (164 studies, 92%). Ethnicity (24%) and co-morbidities (25%) were less frequently reported. Clinical baseline variables included endocrine (60%), ophthalmic (34%), nasal (7%), and cognitive (5%). Preoperative radiological variables were described in 132 studies (74%). MRI alone was the most utilised imaging modality (67%). Further specific radiological baseline variables included: tumour diameter (52 studies, 39%); tumour volume (28 studies, 21%); cavernous sinus invasion (53 studies, 40%); Wilson Hardy grade (25 studies, 19%); Knosp grade (36 studies, 27%). Conclusions: There is heterogeneity in the reporting of baseline variables in patients undergoing transsphenoidal surgery for pituitary adenoma. This review supports the need to develop a common data element to facilitate meaningful comparative research, trial design, and reduce research inefficiency

The mutational impact of culturing human pluripotent and adult stem cells

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies

Reported outcomes in transsphenoidal surgery for pituitary adenomas: a systematic review.

Funder: NIHR Cambridge Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100018956Funder: NIHR Biomedical Research Centre University College LondonFunder: Royal College of SurgeonsFunder: Wellcome Trust (ISSF fund)PURPOSE: Transsphenoidal surgery is an established treatment for pituitary adenomas. We examined outcomes and time points following transsphenoidal surgery for pituitary adenoma to identify reporting heterogeneity within the literature. METHODS: A systematic review of studies that reported outcomes for transsphenoidal surgery for pituitary adenoma 1990-2021 were examined. The protocol was registered a priori and adhered to the PRISMA statement. Studies in English with > 10 patients (prospective) or > 500 patients (retrospective) were included. RESULTS: 178 studies comprising 427,659 patients were included. 91 studies reported 2 or more adenoma pathologies within the same study; 53 studies reported a single pathology. The most common adenomas reported were growth hormone-secreting (n = 106), non-functioning (n = 101), and ACTH-secreting (n = 95); 27 studies did not state a pathology. Surgical complications were the most reported outcome (n = 116, 65%). Other domains included endocrine (n = 104, 58%), extent of resection (n = 81, 46%), ophthalmic (n = 66, 37%), recurrence (n = 49, 28%), quality of life (n = 25, 19%); and nasal (n = 18, 10%). Defined follow up time points were most reported for endocrine (n = 56, 31%), extent of resection (n = 39, 22%), and recurrence (n = 28, 17%). There was heterogeneity in the follow up reported for all outcomes at different time points: discharge (n = 9),  1 year (n = 69). CONCLUSION: Outcomes and follow up reported for transsphenoidal surgical resection of pituitary adenoma are heterogenous over the last 30 years. This study highlights the necessity to develop a robust, consensus-based, minimum, core outcome set. The next step is to develop a Delphi survey of essential outcomes, followed by a consensus meeting of interdisciplinary experts. Patient representatives should also be included. An agreed core outcome set will enable homogeneous reporting and meaningful research synthesis, ultimately improving patient care

Reported baseline variables in transsphenoidal surgery for pituitary adenoma over a 30 year period: a systematic review.

Funder: Wellcome EPSRC Centre for Interventional and Surgical SciencesFunder: NIHR Academic Clinical FellowshipFunder: Cancer Research UK Predoctoral FellowshipFunder: NIHR Cambridge Biomedical Research Centre (BRC-1215-20014)Funder: NIHR BRC Neuro-oncologyFunder: Senior Lectureship at the School of Clinical Medicine, University of CambridgeFunder: Wellcome Trust; doi: http://dx.doi.org/10.13039/100010269Funder: Royal College of Surgeons of England; doi: http://dx.doi.org/10.13039/501100000297PURPOSE: Heterogeneous reporting in baseline variables in patients undergoing transsphenoidal resection of pituitary adenoma precludes meaningful meta-analysis. We therefore examined trends in reported baseline variables, and degree of heterogeneity of reported variables in 30 years of literature. METHODS: A systematic review of PubMed and Embase was conducted on studies that reported outcomes for transsphenoidal surgery for pituitary adenoma 1990-2021. The protocol was registered a priori and adhered to the PRISMA statement. Full-text studies in English with > 10 patients (prospective), > 500 patients (retrospective), or randomised trials were included. RESULTS: 178 studies were included, comprising 427,659 patients: 52 retrospective (29%); 118 prospective (66%); 9 randomised controlled trials (5%). The majority of studies were published in the last 10 years (71%) and originated from North America (38%). Most studies described patient demographics, such as age (165 studies, 93%) and sex (164 studies, 92%). Ethnicity (24%) and co-morbidities (25%) were less frequently reported. Clinical baseline variables included endocrine (60%), ophthalmic (34%), nasal (7%), and cognitive (5%). Preoperative radiological variables were described in 132 studies (74%). MRI alone was the most utilised imaging modality (67%). Further specific radiological baseline variables included: tumour diameter (52 studies, 39%); tumour volume (28 studies, 21%); cavernous sinus invasion (53 studies, 40%); Wilson Hardy grade (25 studies, 19%); Knosp grade (36 studies, 27%). CONCLUSIONS: There is heterogeneity in the reporting of baseline variables in patients undergoing transsphenoidal surgery for pituitary adenoma. This review supports the need to develop a common data element to facilitate meaningful comparative research, trial design, and reduce research inefficiency

Development of 'Core Outcome Sets' for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings.

INTRODUCTION: Meningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma. METHODS AND ANALYSIS: Two systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups. ETHICS AND DISSEMINATION: Institutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available. TRIAL REGISTRATION NUMBER: COMET study ID 1508