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.

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.

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.

Notochordal and nucleus pulposus marker expression is maintained by sub-populations of adult human nucleus pulposus cells through aging and degeneration.

The nucleus pulposus (NP) of the intervertebral disc (IVD) demonstrates substantial changes in cell and matrix composition with both ageing and degeneration. While recent transcriptomic profiling studies have helped define human NP cell phenotype, it remains unclear how expression of these markers is influenced by ageing or degeneration. Furthermore, cells of the NP are thought to derive from the notochord, although adult NP lacks identifiable notochordal (NC) cells. This study aimed to confirm expression of previously identified NP and NC marker genes in adult human NP cells from a range of ages and degenerate states. Importantly, using gene expression analysis (N = 60) and immunohistochemistry (N = 56) the study demonstrates expression of NP markers FoxF1, Pax-1, keratin-8/18, carbonic anhydrase-12, and NC markers brachyury, galectin-3 and CD24 in cells of the NP irrespective of age or degeneration. Our immunohistochemical data, combined with flow cytometry (N = 5) which identified a small number of CA12+Gal3+T+CD24+ cells, suggests the possible presence of a sub-population of cells with an NC-like phenotype in adult NP tissue. These findings suggest that the NP contains a heterogeneous population of cells, which may possess varied phenotypic and functional profiles and thus warrant further investigation to improve our understanding of IVD homeostasis and repair.

Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy.

PURPOSE: In pituitary apoplexy (PA), there are preliminary reports on the appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of this study was to evaluate the incidence and clinical significance of SSMT in patients with PA and a control group of surgically treated non-functioning pituitary adenomas (NFPAs). METHODS: Retrospective review of clinical and imaging variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic regression was used to identify factors associated with SSMT. RESULTS: There were 50 NFPA and 47 PA patients. PA patients were managed conservatively (N = 11) or surgically (N = 36). The median sphenoid sinus mucosal thickness was greater in the PA than NFPA groups (2.0 vs. 0.5 mm; p < 0.001). In multivariate analysis of both the PA and NFPA groups, the presence of PA was the only factor associated with SSMT (OR 0.043, 95% CI 0.012-0.16; p < 0.001). In multivariate analysis of the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR 0.12, 95% CI 0.026-0.54; p = 0.006) and a more severe grade of apoplexy (OR 7.29, 95% CI 1.10-48.40; p = 0.04), were associated with SSMT. CONCLUSION: The incidence of SSMT is higher in patients with PA, especially during the acute phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory and/or infective changes.

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

BACKGROUND: A variety of methods are used for estimating pituitary tumour size in clinical practice and in research. Quantitative methods, such as maximum tumour dimension, and qualitative methods, such as Hardy and Knosp grades, are well established but do not give an accurate assessment of the tumour volume. We therefore sought to compare existing measures of pituitary tumours with more quantitative methods of tumour volume estimation. METHOD: Magnetic resonance imaging was reviewed for 99 consecutive patients with pituitary adenomas awaiting surgery between 2010 and 2013. Maximal tumour diameter, Hardy and Knosp grades were compared with tumour volume estimates by the ellipsoid equation, [4/3π (a,b,c)], (i.e. ellipsoid volume) and slice-by-slice perimetry (i.e. perimeter volume). RESULTS: Ellipsoid and perimeter methods of tumour volume estimation strongly correlated (R(2) = 0.99, p < 0.0001). However the correlation was less strong with increasing tumour size, with the ellipsoid method slightly underestimating. The mean differences were -0.11 (95 % CI, -0.35, 0.14), -0.74 (95 % CI, -2.2, 0.74) and -1.4 (95 % CI, -6.4, 3.7) for micro-tumours, macro-tumours and giant tumours respectively. Tumour volume correlated with maximal diameter, following a cubic distribution. Correlations of tumour volume with Hardy and Knosp grades was less strong. CONCLUSIONS: Perimeter and ellipsoid methods give a good estimation of tumour volume, whereas Knosp and Hardy grades may offer other clinically relevant information, such as cavernous sinus invasion or chiasmal compression. Thus the different methods of estimating tumour size are likely to have different clinical utilities.

Myofibroma of the cervical spine presenting as brachialgia.

Myofibromas are rare, benign tumors of myofibroblasts. Their occurrence in adults, involving bone outside of the head and neck, is especially uncommon. The authors report the case of a 34-year-old woman who presented with left-sided brachialgia. Magnetic resonance imaging identified an expansile soft-tissue lesion of the C6-7 facet joint. En bloc resection via a left posterior midline approach was undertaken. Histopathological analysis confirmed the lesion to be a myofibroma. Brachialgia resolved following surgery and there is no evidence of recurrence at 20 months follow-up. Myofibroma is a rare cause of primary soft-tissue tumor of the spine. Surgical excision remains the mainstay of treatment.

Improving levels of evidence in studies published in spinal journals from 1983 to 2011.

INTRODUCTION: The evidence basis for spinal surgical practice is closely related to the quality of clinical studies published. In the hierarchy of study designs, the quality of evidence from a randomised controlled trial (RCT) and meta-analysis are considered better than other types of prospective and retrospective study designs. We assessed the level of evidence in studies published from 1983 to 2011 in 4 journals, publishing predominantly on spine related topics. METHODS: Computerised search of the Medline database was undertaken to evaluate the articles published in 4 'spinal' journals (Spine, European Spine Journal, Journal of Spinal Disorders and Techniques and Spinal Cord) from 1983 to 2011. The numbers of RCTs, meta-analyses and other clinical trials (non-RCT) over the time periods 1983-7, 1988-92, 1993-7, 1998-2002, 2003-7 and 2008-11 were compared. RESULTS: From a total number of 21775 articles evaluated, there were 888 (4.1%) RCTs, 93 (0.4%) meta-analyses and 1355 (6.2%) other clinical trials. Overall, comparing the time periods 1983-7 with 2008-11, there were increases in the proportion of RCTs (1.6% to 5.1%), meta-analysis (0% to 0.6%) and other clinical trials (0.9% to 6.3%) and a decrease in the proportion of other articles published (97.6% to 88.1%). These changes appear to have plateaued after 2003-7. CONCLUSIONS: Although RCTs, meta-analysis and other clinical trials form a small proportion of the studies published in leading 'spinal' journals, there have been an encouraging increase in their proportion over the years. This is comparable with other larger surgical specialities and provides a better evidence basis for clinical practice in spinal disorders.

Visual loss from a pituitary mass: collision tumors of prostatic metastasis and suprasellar meningioma.

Central nervous system spread from prostate cancer is typically associated with raised prostate specific antigen (PSA) levels. The authors describe a unique case of a "collision tumor" of a prostatic metastasis to the pituitary, juxtaposed to a suprasellar meningioma, with normal PSA levels. This case also emphasizes the need to consider prostatic metastasis in the differential diagnosis of a pituitary mass in patients with a known prostatic cancer, despite the normal PSA levels.

Acromegaly surgery in Manchester revisited--the impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission.

INTRODUCTION: Surgical remission rates for acromegaly vary and are dependent on the tumour morphology, biochemical definition of disease remission and surgical expertise. A previous report from the Manchester region in 1998 reported an overall surgical remission rate of 27% using accepted criteria for biochemical remission at the time. The establishment of the 2010 Consensus guidelines further tightens biochemical criteria for remission. This report aims to assess the impact of establishing a specialist pituitary surgery service in Manchester in 2005, with reduced surgeon numbers on the remission rates for acromegaly surgery. METHODS: Patients with acromegaly undergoing first time endoscopic transsphenoidal surgery between 2005 and 2010 were studied. Surgery was performed by a single surgeon. Review of a prospectively collected acromegaly surgery database was performed with documentation of pre- and postoperative biochemical tests [oral glucose tolerance test (oGTT) and IGF-1], as well as clinical, pathological and radiological data. Definition of disease remission was according to the 2010 Consensus criteria (GH nadir <0·4 µg/l following an oGTT and normalized population matched IGF-1). RESULTS: There were 43 consecutive patients with acromegaly, with 13 (30%) microadenomas and 12 (28%) invasive adenomas. Overall, surgical remission was achieved in 29 (67%) patients. The remission rates were similar between micro (77%), macro (63%) and giant (67%) adenomas. There were nonsignificant trends towards higher remission rates for noninvasive tumours compared with invasive tumours (74%vs 50%) and for patients with a preoperative GH nadir <10 µg/l (73%vs 54%) and IGF-1 standard deviation score <15 (72%vs 54%). CONCLUSIONS: Remission rates for acromegaly surgery have improved following establishment of a specialist surgical service, with a reduction in surgeon numbers. Endoscopic trans-sphenoidal surgery remains an effective first-line treatment for achieving biochemical remission in acromegaly, despite the introduction of the more stringent 2010 consensus guidelines.

Extraventricular neurocytoma of the sellar region.

OBJECTIVE: Extra-ventricular neurocytoma (EVN) is rare, mainly described within the cerebral hemispheres or spinal cord. We report a case of sellar neurocytoma presenting with chiasmal compression. CLINICAL PRESENTATION: A 50-year-old woman presented with decreasing vision and a bitemporal field deficit. CT and MRI demonstrated an enhancing invasive sellar lesion extending into the sphenoid sinus and left cavernous sinus, with speckled calcification and compression of the optic chiasm. Pituitary function was normal apart from a mildly elevated prolactin level consistent with stalk effect. INTERVENTION: Endoscopic trans-sphenoidal resection of the lesion was performed revealing a firm, vascular tumour. Some residual tumour was left within the left cavernous sinus. Histology revealed a neurocytic tumour with nests, islands and strands of neuropil. Diffuse synaptophysin, chromogranin, neurofilament protein and CD56 positivity was seen. A histological diagnosis of EVN, WHO grade II was made and adjuvant radiotherapy was given for the residual tumour. CONCLUSION: This is only the second case of neurocytoma of the sella reported. It should be considered in the differential diagnoses of sellar lesions that appear radiologically atypical for pituitary adenomas.

Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

OBJECT: The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). METHODS: The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. RESULTS: Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p < 0.05). Individually, a mild increase in symptom severity was seen for symptoms attributable to the nasal trauma of surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p < 0.05). Progressive improvements in symptom severity were seen for symptoms more attributable to tumor mass preoperatively (for example, headaches and painkiller use [p < 0.05]). In total, by final follow-up 8 patients (9%) required further treatment or advice for ongoing nasal symptoms. CONCLUSIONS: Endoscopic transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.