Current and Future Advances in Surgical Therapy for Pituitary Adenoma

The vital physiological role of the pituitary gland, alongside its proximal critical neurovascular structures means pituitary adenomas cause significant morbidity or mortality. Whilst enormous advancements have been made in the surgical care of pituitary adenomas, treatment failure and recurrence remain challenges. To meet these clinical challenges, there has been an enormous expansion of novel medical technologies (e.g. endoscopy, advanced imaging, artificial intelligence). These innovations have the potential to benefit each step of the patient journey, and ultimately, drive improved outcomes. Earlier and more accurate diagnosis addresses this in part. Analysis of novel patient data sets, such as automated facial analysis or natural language processing of medical records holds potential in achieving an earlier diagnosis. After diagnosis, treatment decision-making and planning will benefit from radiomics and multimodal machine learning models. Surgical safety and effectiveness will be transformed by smart simulation methods for trainees. Next-generation imaging techniques and augmented reality will enhance surgical planning and intraoperative navigation. Similarly, the future armamentarium of pituitary surgeons, including advanced optical devices, smart instruments and surgical robotics, will augment the surgeon's abilities. Intraoperative support to team members will benefit from a surgical data science approach, utilising machine learning analysis of operative videos to improve patient safety and orientate team members to a common workflow. Postoperatively, early detection of individuals at risk of complications and prediction of treatment failure through neural networks of multimodal datasets will support earlier intervention, safer hospital discharge, guide follow-up and adjuvant treatment decisions. Whilst advancements in pituitary surgery hold promise to enhance the quality of care, clinicians must be the gatekeepers of technological translation, ensuring systematic assessment of risk and benefit. In doing so, the synergy between these innovations can be leveraged to drive improved outcomes for patients of the future

Specialised Surgical Instruments for Endoscopic and Endoscope-Assisted Neurosurgery: A Systematic Review of Safety, Efficacy and Usability

While there have been great strides in endoscopic and endoscope-assisted neurosurgical approaches, particularly in the treatment of deep-sited brain and skull base tumours, the greatest technical barrier to their adoption has been the availability of suitable surgical instruments. This systematic review seeks to identify specialised instruments for these approaches and evaluate their safety, efficacy and usability. Conducted in accordance with the PRISMA guidelines, Medline, Embase, CENTRAL, SCOPUS and Web of Science were searched. Original research studies that reported the use of specialised mechanical instruments that manipulate tissue in human patients, cadavers or surgical models were included. The results identified 50 specialised instruments over 62 studies. Objective measures of safety were reported in 32 out of 62 studies, and 20 reported objective measures of efficacy. Instruments were broadly safe and effective with one instrument malfunction noted. Measures of usability were reported in 15 studies, with seven reporting on ergonomics and eight on the instruments learning curve. Instruments with reports on usability were generally considered to be ergonomic, though learning curve was often considered a disadvantage. Comparisons to standard instruments were made in eight studies and were generally favourable. While there are many specialised instruments for endoscopic and endoscope-assisted neurosurgery available, the evidence for their safety, efficacy and usability is limited with non-standardised reporting and few comparative studies to standard instruments. Future innovation should be tailored to unmet clinical needs, and evaluation guided by structured development processes

Robotic Handle Prototypes for Endoscopic Endonasal Skull Base Surgery: Pre-clinical Randomised Controlled Trial of Performance and Ergonomics

Endoscopic endonasal skull base surgery is a promising alternative to transcranial approaches. However, standard instruments lack articulation, and thus, could benefit from robotic technologies. The aim of this study was to develop an ergonomic handle for a handheld robotic instrument intended to enhance this procedure. Two different prototypes were developed based on ergonomic guidelines within the literature. The first is a forearm-mounted handle that maps the surgeon’s wrist degrees-of-freedom to that of the robotic end-effector; the second is a joystick-and-trigger handle with a rotating body that places the joystick to the position most comfortable for the surgeon. These handles were incorporated into a custom-designed surgical virtual simulator and were assessed for their performance and ergonomics when compared with a standard neurosurgical grasper. The virtual task was performed by nine novices with all three devices as part of a randomised crossover user-study. Their performance and ergonomics were evaluated both subjectively by themselves and objectively by a validated observational checklist. Both handles outperformed the standard instrument with the rotating joystick-body handle offering the most substantial improvement in terms of balance between performance and ergonomics. Thus, it is deemed the more suitable device to drive instrumentation for endoscopic endonasal skull base surgery

Process analysis of the patient pathway for automated data collection: an exemplar using pituitary surgery

Introduction: Automation of routine clinical data shows promise in relieving health systems of the burden associated with manual data collection. Identifying consistent points of documentation in the electronic health record (EHR) provides salient targets to improve data entry quality. Using our pituitary surgery service as an exemplar, we aimed to demonstrate how process mapping can be used to identify reliable areas of documentation in the patient pathway to target structured data entry interventions. Materials and methods: This mixed methods study was conducted in the largest pituitary centre in the UK. Purposive snowball sampling identified frontline stakeholders for process mapping to produce a patient pathway. The final patient pathway was subsequently validated against a real-world dataset of 50 patients who underwent surgery for pituitary adenoma. Events were categorized by frequency and mapped to the patient pathway to determine critical data points. Results: Eighteen stakeholders encompassing all members of the multidisciplinary team (MDT) were consulted for process mapping. The commonest events recorded were neurosurgical ward round entries (N = 212, 14.7%), pituitary clinical nurse specialist (CNS) ward round entries (N = 88, 6.12%) and pituitary MDT treatment decisions (N = 88, 6.12%) representing critical data points. Operation notes and neurosurgical ward round entries were present for every patient. 43/44 (97.7%) had a pre-operative pituitary MDT entry, pre-operative clinic letter, a post-operative clinic letter, an admission clerking entry, a discharge summary, and a post-operative histopathology pituitary multidisciplinary (MDT) team entries. Conclusion: This is the first study to produce a validated patient pathway of patients undergoing pituitary surgery, serving as a comparison to optimise this patient pathway. We have identified salient targets for structured data entry interventions, including mandatory datapoints seen in every admission and have also identified areas to improve documentation adherence, both of which support movement towards automation

The clinical outcomes of imaging modalities for surgical management Cushing’s disease – A systematic review and meta-analysis

INTRODUCTION: Cushing’s disease presents major diagnostic and management challenges. Although numerous preoperative and intraoperative imaging modalities have been deployed, it is unclear whether these investigations have improved surgical outcomes. Our objective was to investigate whether advances in imaging improved outcomes for Cushing’s disease. METHODS: Searches of PubMed and EMBASE were conducted. Studies reporting on imaging modalities and clinical outcomes after surgical management of Cushing’s disease were included. Multilevel multivariable meta-regressions identified predictors of outcomes, adjusting for confounders and heterogeneity prior to investigating the effects of imaging. RESULTS: 166 non-controlled single-arm studies were included, comprising 13181 patients over 44 years. The overall remission rate was 77.0% [CI: 74.9%-79.0%]. Cavernous sinus invasion (OR: 0.21 [CI: 0.07-0.66]; p=0.010), radiologically undetectable lesions (OR: 0.50 [CI: 0.37–0.69]; p<0.0001), previous surgery (OR=0.48 [CI: 0.28–0.81]; p=0.008), and lesions ≥10mm (OR: 0.63 [CI: 0.35–1.14]; p=0.12) were associated with lower remission. Less stringent thresholds for remission was associated with higher reported remission (OR: 1.37 [CI: 1.1–1.72]; p=0.007). After adjusting for this heterogeneity, no imaging modality showed significant differences in remission compared to standard preoperative MRI. The overall recurrence rate was 14.5% [CI: 12.1%-17.1%]. Lesion ≥10mm was associated with greater recurrence (OR: 1.83 [CI: 1.13–2.96]; p=0.015), as was greater duration of follow-up (OR: 1.53 (CI: 1.17–2.01); p=0.002). No imaging modality was associated with significant differences in recurrence. Despite significant improvements in detection rates over four decades, there were no significant changes in the reported remission or recurrence rates. CONCLUSION: A lack of controlled comparative studies makes it difficult to draw definitive conclusions. Within this limitation, the results suggest that despite improvements in radiological detection rates of Cushing’s disease over the last four decades, there were no changes in clinical outcomes. Advances in imaging alone may be insufficient to improve surgical outcomes. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020187751

Skull base repair following endonasal pituitary and skull base tumour resection: a systematic review.

PURPOSE: Postoperative cerebrospinal fluid rhinorrhoea (CSFR) remains a frequent complication of endonasal approaches to pituitary and skull base tumours. Watertight skull base reconstruction is important in preventing CSFR. We sought to systematically review the current literature of available skull base repair techniques. METHODS: Pubmed and Embase databases were searched for studies (2000-2020) that (a) reported on the endonasal resection of pituitary and skull base tumours, (b) focussed on skull base repair techniques and/or postoperative CSFR risk factors, and (c) included CSFR data. Roles, advantages and disadvantages of each repair method were detailed. Random-effects meta-analyses were performed where possible. RESULTS: 193 studies were included. Repair methods were categorised based on function and anatomical level. There was absolute heterogeneity in repair methods used, with no independent studies sharing the same repair protocol. Techniques most commonly used for low CSFR risk cases were fat grafts, fascia lata grafts and synthetic grafts. For cases with higher CSFR risk, multilayer regimes were utilized with vascularized flaps, gasket sealing and lumbar drains. Lumbar drain use for high CSFR risk cases was supported by a randomised study (Oxford CEBM: Grade B recommendation), but otherwise there was limited high-level evidence. Pooled CSFR incidence by approach was 3.7% (CI 3-4.5%) for transsphenoidal, 9% (CI 7.2-11.3%) for expanded endonasal, and 5.3% (CI 3.4-7%) for studies describing both. Further meaningful meta-analyses of repair methods were not performed due to significant repair protocol heterogeneity. CONCLUSIONS: Modern reconstructive protocols are heterogeneous and there is limited evidence to suggest the optimal repair technique after pituitary and skull base tumour resection. Further studies are needed to guide practice

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection

Abstract: Purpose: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. Methods: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. Results: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. Conclusions: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed “core” steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The “optional” steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Intraoperative Ultrasound in Patients Undergoing Transsphenoidal Surgery for Pituitary Adenoma: Systematic Review

Transsphenoidal surgery is the gold standard for pituitary adenoma resection. However, despite advances in microsurgical and endoscopic techniques, some pituitary adenomas can be challenging to cure.status: publishe