Value of Early Post-Operative Growth Hormone Testing in Predicting Long-Term Remission and Residual Disease after Transsphenoidal Surgery for Acromegaly.

INTRODUCTION: Surgical remission for acromegaly is dependent on a number of factors including tumour size, invasiveness, and surgical expertise. We studied the value of early post-operative growth hormone (GH) level as a predictor of outcome and to guide early surgical re-exploration for residual disease in patients with acromegaly. METHODS: Patients with acromegaly undergoing first-time endoscopic transsphenoidal surgery between 2005 and 2015, in 2 regional neurosurgical centres, were studied. Insulin-like growth factor-1 (IGF-1), basal GH (i.e., sample before oral glucose), and GH nadir on oral glucose tolerance test (OGTT) were tested at various time points, including 2-5 days post-operatively. Definition of disease remission was according to the 2010 consensus statement (i.e., GH nadir <0.4 µg/L during an OGTT and normalized population-matched IGF-1). Forward stepwise logistic regression was used to determine factors associated with remission. RESULTS: We investigated 81 consecutive patients with acromegaly, 67 (83%) of which had macroadenomas and 22 (27%) were noted to be invasive at surgery. Mean follow-up was 44 ± 25 months. Overall, surgical remission was achieved in 55 (68%) patients at final follow-up. On univariate analysis, the remission rates at the end of the study period for patients with early post-operative GH nadir on OGTT of <0.4 (N = 43), between 0.4 and 1 (N = 28), and >1 µg/L (N = 8) were 88, 54, and 20%, respectively. Similar results were seen with basal GH on early post-operative OGTT. On multivariate regression analysis, pre-operative IGF-1 (odds ratio of 13.1) and early post-operative basal GH (odds ratio of 5.0) and GH nadir on OGTT (odds ratio of 6.8) were significant predictors of residual disease. Based on a raised early GH nadir and post-operative MR findings, 10 patients underwent early surgical re-exploration. There was reduction in post-operative GH levels in 9 cases, of which 5 (50%) achieved long-term remission. There was an increased risk of new pituitary hormone deficiencies in patients having surgical re-exploration compared to those having a single operation (60 vs. 14%). CONCLUSIONS: An early post-operative basal GH and GH nadir on OGTT are reliable predictors of long-term disease remission. It can be used to guide patients for early surgical re-exploration for residual disease, although there is increased risk of hypopituitarism.

Venous thromboembolism chemical prophylaxis after endoscopic trans-sphenoidal pituitary surgery.

PURPOSE: There is no compelling outcome data or clear guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using low molecular weight heparin (chemoprophylaxis) in patients undergoing pituitary surgery. Here we describe our experience of early chemoprophylaxis (post-operative day 1) following trans-sphenoidal pituitary surgery. METHODS: Single-centre review of a prospective surgical database and VTE records. Adults undergoing first time trans-sphenoidal pituitary surgery were included (2009-2018). VTE was defined as either deep vein thrombosis and/or pulmonary embolism within 3 months of surgery. Postoperative haematomas were those associated with a clinical deterioration together with radiological evidence. RESULTS: 651 Patients included with a median age of 55 years (range 16-86 years). Most (99%) patients underwent trans-sphenoidal surgery using a standard endoscopic single nostril or bi-nostril trans-sphenoidal technique. More than three quarters had pituitary adenomas (n = 520, 80%). Postoperative chemoprophylaxis to prevent VTE was administered in 478 patients (73%). Chemoprophylaxis was initiated at a median of 1 day post-procedure (range 1-5 days postoperatively; 92% on postoperative day 1). Tinzaparin was used in 465/478 patients (97%) and enoxaparin was used in 14/478 (3%). There were no cases of VTE, even in 78 ACTH-dependent Cushing's disease patients. Six patients (1%) developed postoperative haematomas. Chemoprophylaxis was not associated with a significantly higher rate of postoperative haematoma formation (Fisher's Exact, p = 0.99) or epistaxis (Fisher's Exact, p > 0.99). CONCLUSIONS: Chemoprophylaxis after trans-sphenoidal pituitary surgery on post-operative day 1 is a safe strategy to reduce the risk of VTE without significantly increasing the risk of postoperative bleeding events.

Pre- and postoperative need for pituitary hormone replacement in non-adenomatous sellar and parasellar lesions: importance of the sellar encroachment score.

BACKGROUND: Pre-/postoperative pituitary endocrine deficiencies in patients with sellar/parasellar non-adenomatous lesions are poorly described and studies have not considered the effect of sellar invasion on endocrine outcome. The aim of this study was to relate the need for pituitary hormone replacement pre-/postoperatively, with sellar invasion, in non-adenomatous sellar/parasellar lesions. METHODS: Single-centre review of adults with histologically confirmed non-adenomatous sellar/parasellar lesion and follow-up ≥ 3 months or until postop radiotherapy. Pituitary dysfunction was defined by hormone replacement. The sellar encroachment score (0-6) was calculated as the sum of the thirds of radiological encroachment into the sellar region in the coronal and sagittal planes. Multivariate analysis with binary logistic regression was used to determine factors associated with pituitary hormone replacement. RESULTS: One hundred and seventeen patients were included with a median age of 49 years (range 16-84 years) and median follow-up of 13 months. Surgery was trans-sphenoidal (53%), trans-cranial (36%) or a combination (11%). The commonest histology types were meningioma (n = 33, 28%) and craniopharyngioma (n = 20, 17%). The median sellar encroachment score was 6 (range 0-6). Most (n = 86, 74%) did not require pituitary hormone replacement preoperatively. The need for pituitary hormones increased after surgery in 41 (35%) patients. In multivariate analysis, the sellar encroachment score was the only factor predictive of pre- (OR = 2.6, 95% CI = 1.2-5.5; p = 0.01) and postoperative risk of new pituitary hormone replacement (OR = 4.1, 95% CI = 1.7-10.1, p = 0.002). CONCLUSION: A significant proportion of these patients present with need for pituitary hormone replacement that may worsen postoperatively. The degree of sellar encroachment is predictive of pituitary hormone replacement status pre-/postoperatively.

Trends in the quality of work presented at the society of british neurological surgeons meetings: 1975 to 2010.

BACKGROUND: The quality of scientific publications in clinical journals is well studied but the quality of work presented at medical conferences less so. AIMS: To describe trends in the quality of presentations at the Society of British Neurological Surgeons [SBNS] conference between 1975 and 2010 and the factors associated with higher quality work in order to consider what might improve publication rates. METHODS: Analysis was conducted in 5-year time periods (i.e. 1975-1979, 1985-1989, 1995-1999, 2005-2009). Published abstracts were used to identify conference presentations. Quality metrics included level of evidence of the presentation and eventual publication within 5 years. Publication 5-year citation count and destination journal impact factor were further used to assess publication quality. Statistical analysis was carried out using SPSS. RESULTS: Of the 1711 presentations in total, 479 (28%) were published. The British Journal of Neurosurgery (93, 19%) was the favoured destination. Although the total number of publications has increased, given the increase in the number of presentations, the proportion of work published has decreased (80/179; 45% in the 1970s to 113/721; 16% in the 2000s). The growth in the impact factor of published work was better than that found in leading neurosurgical journals, but lower than for leading medical journals. In a multivariate model, presentations using a higher level of evidence increased the likelihood of publication (AOR 6.7 95% CI 3.7, 12.1), whilst presenting at conferences after the 1970s reduced the likelihood of publication; 1985-1989 (AOR 0.3, 95% CI 0.2, 0.4), 1995-1999 (0.4, 95% CI 0.3, 0.7) and 2005-2009 (0.1, 95% CI 0.1, 0.2). CONCLUSION: SBNS conferences today contain more presentations and yield more publications than ever before. However, the increased volume may dilute the quality of work presented.

Correction to: Assessing size of pituitary adenomas: a comparison of qualitative and quantitative methods on MR.

We have incorrectly described the ellipsoid equation as being calculated using maximal diameters. It is in fact calculated using half the maximal diameter, i.e. the maximal radii. The diameter is initially recorded on the MRI images (as per Fig. 1), as the lesions do not have a defined midpoint.

Sphenoid sinus microbiota in pituitary apoplexy: a preliminary study.

PURPOSE: There is a high incidence of abnormal sphenoid sinus changes in patients with pituitary apoplexy (PA). Their pathophysiology is currently unexplored and may reflect an inflammatory or infective process. In this preliminary study, we characterised the microbiota of sphenoid sinus mucosa in patients with PA and compared findings to a control group of surgically treated non-functioning pituitary adenomas (NFPAs). METHODS: In this prospective observational study of patients undergoing trans-sphenoidal surgery for PA or NFPA, sphenoid sinus mucosal specimens were microbiologically profiled through PCR-cloning of the 16S rRNA gene. RESULTS: Ten patients (five with PA and five with NFPAs) with a mean age of 51 years (range 23-71) were included. Differences in the sphenoid sinus microbiota of the PA and NFPA groups were observed. Four PA patients harboured Enterobacteriaceae (Enterobacter spp., N = 3; Escherichia coli, N = 1). In contrast, patients with NFPAs had a sinus microbiota more representative of health, including Staphylococcus epidermidis (N = 2) or Corynebacterium spp. (N = 2). CONCLUSIONS: PA may be associated with an abnormal sphenoid sinus microbiota that is similar to that seen in patients with sphenoid sinusitis.

Transient Exacerbation of Nasal Symptoms following Endoscopic Transsphenoidal Surgery for Pituitary Tumors: A Prospective Study.

Object Endoscopic transsphenoidal surgery is the commonest approach to pituitary tumors. One disadvantage of this approach is the development of early postoperative nasal symptoms. Our aim was to clarify the peak onset of these symptoms and their temporal evolution. Methods The General Nasal Patient Inventory (GNPI) was administered to 56 patients undergoing endoscopic transsphenoidal surgery for pituitary tumors preoperatively and at 1 day, 3 days, 2 weeks, 3 months, and 6 to 12 months postoperatively. Most patients underwent surgery for pituitary adenomas ( N = 49; 88%) and through a uninostril approach ( N = 55; 98%). Total GNPI (0-135) and scores for the 45 individual components were compared. Results GNPI scores peaked at 1 to 3 days postoperatively, with rapid reduction to baseline by 2 weeks and below baseline by 6 to 12 months postsurgery ( p < 0.01). Of the 45 individual symptoms on the GNPI scale, 19 (42%) worsened transiently after surgery ( p < 0.05). Functioning tumors had a higher GNPI scores at postoperative day 1 and 3 than nonfunctioning tumors, although their temporal evolution was the same ( p < 0.05). Conclusions Nasal morbidity following endoscopic transsphenoidal pituitary surgery is common, but transient, more so in the functioning subgroup. Nasal symptoms improve below baseline by 6 to 12 months, without the need for specific long-term postoperative interventions in the vast majority of patients.