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), < 30 days (n = 23), < 6 months (n = 64), < 1 year (n = 23), and > 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.

Lumbar decompression surgery for cauda equina syndrome - comparison of complication rates between daytime and overnight operating.

PURPOSE: To investigate the incidence of complications from lumbar decompression ± discectomy surgery for cauda equina syndrome (CES), assessing whether time of day is associated with a change in the incidence of complications. METHODS: Electronic clinical and operative notes for all lumbar decompression operations undertaken at our institution for CES over a 2-year time period were retrospectively reviewed. "Overnight" surgery was defined as any surgery occurring between 18:00 and 08:00 on any day. Clinicopathological characteristics, surgical technique, and peri/post-operative complications were recorded. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals. RESULTS: A total of 81 lumbar decompression operations were performed in the 2-year period and analysed. A total of 29 (36%) operations occurred overnight. Complete CES (CESR) was seen in 13 cases (16%) in total, 7 of whom underwent surgery during the day. Exactly 27 complications occurred in 24 (30%) patients. The most frequently occurring complication was a dural tear (n = 21, 26%), followed by post-operative haematoma, infection, and residual disc. Complication rates in the CESR cohort (54%) were significantly greater than in the CES incomplete (CESI) cohort (25%) (p = 0.04). On multivariable analysis, overnight surgery was independently associated with a significantly increased complication rate (OR 2.83, CI 1.02-7.89). CONCLUSIONS: Lumbar decompressions performed overnight for CES were more than twice as likely to suffer a complication, in comparison to those performed within daytime hours. Our study suggests that out-of-hours operating, particularly at night, must be clinically justified and should not be influenced by day-time operating capacity.

Long-term oncological outcomes after haemorrhagic apoplexy in pituitary adenoma managed operatively and non-operatively.

INTRODUCTION: Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively. METHODS: Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up. RESULTS: One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups. CONCLUSION: Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.

CSF rhinorrhoea after endonasal intervention to the anterior skull base (CRANIAL): proposal for a prospective multicentre observational cohort study.

BACKGROUND: The endonasal transsphenoidal approach (TSA) has emerged as the preferred approach in order to treat pituitary adenoma and related sellar pathologies. The recently adopted expanded endonasal approach (EEA) has improved access to the ventral skull base whilst retaining the principles of minimally invasive surgery. Despite the advantages these approaches offer, cerebrospinal fluid (CSF) rhinorrhoea remains a common complication. There is currently a lack of comparative evidence to guide the best choice of skull base reconstruction, resulting in considerable heterogeneity of current practice. This study aims to determine: (1) the scope of the methods of skull base repair; and (2) the corresponding rates of postoperative CSF rhinorrhoea in contemporary neurosurgical practice in the UK and Ireland. METHODS: We will adopt a multicentre, prospective, observational cohort design. All neurosurgical units in the UK and Ireland performing the relevant surgeries (TSA and EEA) will be eligible to participate. Eligible cases will be prospectively recruited over 6 months with 6 months of postoperative follow-up. Data points collected will include: demographics, tumour characteristics, operative data), and postoperative outcomes. Primary outcomes include skull base repair technique and CSF rhinorrhoea (biochemically confirmed and/or requiring intervention) rates. Pooled data will be analysed using descriptive statistics. All skull base repair methods used and CSF leak rates for TSA and EEA will be compared against rates listed in the literature. ETHICS AND DISSEMINATION: Formal institutional ethical board review was not required owing to the nature of the study - this was confirmed with the Health Research Authority, UK. CONCLUSIONS: The need for this multicentre, prospective, observational study is highlighted by the relative paucity of literature and the resultant lack of consensus on the topic. It is hoped that the results will give insight into contemporary practice in the UK and Ireland and will inform future studies.

PET-guided repeat transsphenoidal surgery for previously deemed unresectable lateral disease in acromegaly.

OBJECTIVE: The object of this study was to determine if revision transsphenoidal surgery (TSS), guided by 11C-methionine PET/CT coregistered with volumetric MRI (Met-PET/MRCR), can lead to remission in patients with persistent acromegaly due to a postoperative lateral disease remnant. METHODS: The authors identified 9 patients with persistent acromegaly following primary intervention (TSS ± medical therapy ± radiotherapy) in whom further surgery had initially been discounted because of equivocal MRI findings with suspected lateral sellar and/or parasellar disease (cases with clear Knosp grade 4 disease were excluded). All patients underwent Met-PET/MRCR. Scan findings were used by the pituitary multidisciplinary team to inform decision-making regarding repeat surgery. Revision TSS was performed with wide lateral exploration as guided by the PET findings. Endocrine reassessment was performed at 6-10 weeks after surgery, with longitudinal follow-up thereafter. RESULTS: Met-PET/MRCR revealed focal tracer uptake in the lateral sellar and/or parasellar region(s) in all 9 patients, which correlated with sites of suspected residual tumor on volumetric MRI. At surgery, tumor was identified and resected in 5 patients, although histological analysis confirmed somatotroph tumor in only 4 cases. In the other 4 patients, no definite tumor was seen, but equivocal tissue was removed. Despite the uncertainty at surgery, all patients showed immediate significant improvements in clinical and biochemical parameters. In the 8 patients for whom long-term follow-up data were available, insulin-like growth factor 1 (IGF-1) was ≤ 1.2 times the upper limit of normal (ULN) in all subjects and ≤ 1 times the ULN in 6 subjects, and these findings have been maintained for up to 28 months (median 8 months, mean 13 months) with no requirement for adjunctive medical therapy or radiotherapy. No patient suffered any additional pituitary deficit or other complication of surgery. CONCLUSIONS: This study provides proof of concept that Met-PET/MRCR can be helpful in the evaluation of residual lateral sellar/parasellar disease in persistent acromegaly and facilitate targeted revision TSS in a subgroup of patients.

A comparison of semi-automated volumetric vs linear measurement of small vestibular schwannomas.

OBJECTIVE: Accurate and precise measurement of vestibular schwannoma (VS) size is key to clinical management decisions. Linear measurements are used in routine clinical practice but are prone to measurement error. This study aims to compare a semi-automated volume segmentation tool against standard linear method for measuring small VS. This study also examines whether oblique tumour orientation can contribute to linear measurement error. STUDY DESIGN: Experimental comparison of observer agreement using two measurement techniques. SETTING: Tertiary skull base unit. PARTICIPANTS: Twenty-four patients with unilateral sporadic small (< 15 mm maximum intracranial dimension) VS imaged with 1 mm-thickness T1-weighted Gadolinium enhanced MRI. MAIN OUTCOME MEASURES: (1) Intra and inter-observer intraclass correlation coefficients (ICC), repeatability coefficients (RC), and relative smallest detectable difference (%SDD). (2) Mean change in maximum linear dimension following reformatting to correct for oblique orientation of VS. RESULTS: Intra-observer ICC was higher for semi-automated volumetric when compared with linear measurements, 0.998 (95% CI 0.994-0.999) vs 0.936 (95% CI 0.856-0.972), p < 0.0001. Inter-observer ICC was also higher for volumetric vs linear measurements, 0.989 (95% CI 0.975-0.995) vs 0.946 (95% CI 0.880-0.976), p = 0.0045. The intra-observer %SDD was similar for volumetric and linear measurements, 9.9% vs 11.8%. However, the inter-observer %SDD was greater for volumetric than linear measurements, 20.1% vs 10.6%. Following oblique reformatting to correct tumour angulation, the mean increase in size was 1.14 mm (p = 0.04). CONCLUSION: Semi-automated volumetric measurements are more repeatable than linear measurements when measuring small VS and should be considered for use in clinical practice. Oblique orientation of VS may contribute to linear measurement error.

Safety and effectiveness of recombinant human bone morphogenetic protein-2 for spinal fusion: a meta-analysis of individual-participant data.

BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is widely used to promote fusion in spinal surgery, but its safety has been questioned. PURPOSE: To evaluate the effectiveness and safety of rhBMP-2. DATA SOURCES: Individual-participant data obtained from the sponsor or investigators and data extracted from study publications identified by systematic bibliographic searches through June 2012. STUDY SELECTION: Randomized, controlled trials of rhBMP-2 versus iliac crest bone graft (ICBG) in spinal fusion surgery for degenerative disc disease and related conditions and observational studies in similar populations for investigation of adverse events. DATA EXTRACTION: Individual-participant data from 11 eligible of 17 provided trials sponsored by Medtronic (Minneapolis, Minnesota) (n = 1302) and 1 of 2 other eligible trials (n = 106) were included. Additional aggregate adverse event data were extracted from 35 published observational studies. DATA SYNTHESIS: Primary outcomes were pain (assessed with the Oswestry Disability Index [ODI] or Short Form-36), fusion, and adverse events. At 24 months, ODI scores were 3.5% lower (better) with rhBMP-2 than with ICBG (95% CI, 0.5% to 6.5%) and radiographic fusion was 12% higher (CI, 2% to 23%). At or shortly after surgery, pain was more common with rhBMP-2 (odds ratio, 1.78 [CI, 1.06 to 2.95]). Cancer was more common after rhBMP-2 (relative risk, 1.98 [CI, 0.86 to 4.54]), but the small number of events precluded definite conclusions. LIMITATION: The observational studies were diverse and at risk of bias. CONCLUSION: At 24 months, rhBMP-2 increases fusion rates, reduces pain by a clinically insignificant amount, and increases early postsurgical pain compared with ICBG. Evidence of increased cancer incidence is inconclusive. PRIMARY FUNDING SOURCE: Yale University Open Data Access Project.

Best practices for the development, scale-up, and post-approval change control of IR and MR dosage forms in the current quality-by-design paradigm.

In this whitepaper, the Manufacturing Technical Committee of the Product Quality Research Institute provides information on the common, best practices in use today in the development of high-quality chemistry, manufacturing and controls documentation. Important topics reviewed include International Conference on Harmonization, in vitro-in vivo correlation considerations, quality-by-design approaches, process analytical technologies and current scale-up, and process control and validation practices. It is the hope and intent that this whitepaper will engender expanded dialog on this important subject by the pharmaceutical industry and its regulatory bodies.

Real-world experience with 11C-methionine positron emission tomography in the management of acromegaly.

BACKGROUND: L-[methyl-11C]-methionine-positron emission tomography (Met-PET) is a potentially important imaging adjunct in the diagnostic workup of pituitary adenomas, including somatotroph tumors. Met-PET can identify residual or occult disease and make definitive therapies accessible to a subgroup of patients who would otherwise require lifelong medical therapy. However, existing data on its use are still limited to small case series. Here, we report the largest single-center experience (n = 61) in acromegaly. METHODS: A total of 189 cases of acromegaly were referred to our national Met-PET service in the last 12 years. For this analysis, we have reviewed outcomes in those 61 patients managed exclusively by our multidisciplinary team (single center, single surgeon). Referral indications were as follows: indeterminate magnetic resonance imaging (MRI; n = 38, 62.3%), occult residual (n = 14, 23.0%), (radio-)surgical planning (n = 6, 9.8%), and occult de novo tumor (n = 3, 4.9%). RESULTS: A total of 33/61 patients (54.1%) underwent PET-guided surgery. Twenty-four of 33 patients (72.7%) achieved complete biochemical remission following (re-)surgery. Insulin-like growth factor 1 levels were reduced to <2 × upper limit of normal (ULN) in 6 of the remaining 9 cases, 3 of whom achieved levels of <1.1 × ULN compared with mean preoperative levels of 2.4 × ULN (SD 0.8) for n = 9. Only 3 patients developed single new hormonal deficits (gonadotropic/thyrotropic insufficiency). There were no neurovascular complications after surgery. CONCLUSION: In patients with persistent/recurrent acromegaly or occult tumors, Met-PET can facilitate further targeted intervention (surgery/radiosurgery). This led to complete remission in most cases (24/33) or significant improvement with comparatively low risk of complications. L-[methyl-11C]-methionine-positron emission tomography should therefore be considered in all patients who are potential candidates for further surgical intervention but present no clear target on MRI.

Image-guided resection of spheno-orbital skull-base meningiomas with predominant intraosseous component.

BACKGROUND: Although meningiomas of the spheno-orbital region commonly result in hyperostosis, intraosseous meningiomas, which feature extensive full thickness infiltration of the anterolateral skull base, are rare. In this study, we assess the value of image guidance during surgery for intraosseous spheno-orbital skull-base meningiomas in achieving safe and maximal abnormal bone resection. METHOD: Only cases with a full thickness and extensive intraosseous component were included. Image guidance was used to guide drilling of hyperostotic bone. Extensive resulting defects of the orbital wall were reconstructed with titanium mesh. Post-operative CT scans were used to assess completeness of abnormal bone resection in the skull base, and MRI scans used to evaluate residual intradural disease. Operative complications to neurovascular structures in adjacent foramina were recorded. RESULTS: Nineteen patients with full-thickness intraosseous spheno-orbital meningiomas underwent image-guided resection. Anterior clinoidectomy to variable extent was necessary in 11 cases with decompression of the optic canal in five. In ten cases, hyperostotic bone was drilled from the middle fossa around the exit foramina of the trigeminal nerve and base of the pterygoid plates. Proptosis was corrected in all cases, and of 11 patients presenting with reduced visual acuity, symptoms improved or stabilized in ten cases. Post-operative CT scans confirmed gross resection of abnormal bone in all cases, but limited residual tumor was present around the cavernous sinus or orbital apex in eight patients. One patient died from a pulmonary embolism, the only mortality of the series. One patient had worsening of pre-existing poor visual acuity, and three patients had worsening of pre-existing ophthalmoplegia. Five patients developed new facial numbness post-operatively, which persisted in three cases. CONCLUSIONS: Intra-operative image guidance allowed total or near-total resection of the hyperostotic skull base around the cranial nerve foramina with minimal morbidity in a group of patients with extensive spheno-orbital meningiomas.

Development of a bespoke phantom to optimize molecular PET imaging of pituitary tumors.

BACKGROUND: Image optimization is a key step in clinical nuclear medicine, and phantoms play an essential role in this process. However, most phantoms do not accurately reflect the complexity of human anatomy, and this presents a particular challenge when imaging endocrine glands to detect small (often subcentimeter) tumors. To address this, we developed a novel phantom for optimization of positron emission tomography (PET) imaging of the human pituitary gland. Using radioactive 3D printing, phantoms were created which mimicked the distribution of 11C-methionine in normal pituitary tissue and in a small tumor embedded in the gland (i.e., with no inactive boundary, thereby reproducing the in vivo situation). In addition, an anatomical phantom, replicating key surrounding structures [based on computed tomography (CT) images from an actual patient], was created using material extrusion 3D printing with specialized filaments that approximated the attenuation properties of bone and soft tissue. RESULTS: The phantom enabled us to replicate pituitary glands harboring tumors of varying sizes (2, 4 and 6 mm diameters) and differing radioactive concentrations (2 ×, 5 × and 8 × the normal gland). The anatomical phantom successfully approximated the attenuation properties of surrounding bone and soft tissue. Two iterative reconstruction algorithms [ordered subset expectation maximization (OSEM); Bayesian penalized likelihood (BPL)] with a range of reconstruction parameters (e.g., 3, 5, 7 and 9 OSEM iterations with 24 subsets; BPL regularization parameter (ß) from 50 to 1000) were tested. Images were analyzed quantitatively and qualitatively by eight expert readers. Quantitatively, signal was the highest using BPL with ß = 50; noise was the lowest using BPL with ß = 1000; contrast was the highest using BPL with ß = 100. The qualitative review found that accuracy and confidence were the highest when using BPL with ß = 400. CONCLUSIONS: The development of a bespoke phantom has allowed the identification of optimal parameters for molecular pituitary imaging: BPL reconstruction with TOF, PSF correction and a ß value of 400; in addition, for small (< 4 mm) tumors with low contrast (2:1 or 5:1), sensitivity may be improved using a ß value of 100. Together, these findings should increase tumor detection and confidence in reporting scans.

Minimally invasive lumbar decompression: long-term outcome, morbidity, and the learning curve from the first 50 cases.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To describe our experience with the first 50 cases of minimally invasive lumbar canal decompression in terms of patient outcome up to 2 years, the learning curve incurred, and complications when compared with our most recent 50 cases. SUMMARY OF BACKGROUND DATA: Lumbar canal stenosis is a common condition in the elderly population, the symptoms of which respond well to surgical decompression. A minimally invasive approach offers potential short and long-term benefits to patients but the technique is associated with a learning curve and equivalence to open surgery regarding efficacy and complications needs to be demonstrated. METHODS: Fifty patients (mean age 70 y) who presented with clinical and radiological features of lumbar canal stenosis and who had failed a period of conservative management underwent lumbar canal decompression through a paramedian oblique, muscle splitting approach using a 16 to 18 mm operating tube and microscope. Outcome was assessed using the Oswestry Disability Index and Short Form-36 at 3 months, 1 year, and 2 years. RESULTS: Significant clinical improvements were seen at 3 months that were sustained at 1 and 2 years. Clinical outcome improved whereas operative time and complications fell as experience increased, helping to define the learning curve with this technique. CONCLUSIONS: Minimally invasive lumbar decompression seems to offer patients a clinical benefit comparable to that observed in published open series, with potential advantages in terms of postoperative pain and recovery. However, there is a learning curve and whether this technique offers long-term benefits with regard to a reduction in back pain or postoperative spondylolisthesis is not yet known.

A 2 and 5-Year Longitudinal Analysis of 671 Consecutive Patients Diagnosed with Unilateral Vestibular Schwannoma.

OBJECTIVE: To analyse the 2 and 5-year outcomes of a cohort of patients with newly diagnosed vestibular schwannoma patients. STUDY DESIGN: Longitudinal cohort study. SETTING: Tertiary skull base referral unit. PATIENTS: Six hundred and seventy-one consecutive patients referred to the Cambridge Skull Base Unit between 2005 and 2010. MAIN OUTCOME MEASURES: 1) Treatment outcomes, 2) hearing preservation, 3) facial nerve function, and 4) gross tumor control. RESULTS: At initial diagnosis, 440/671(65.6%) of patients entered a watch, wait and rescan (WWR) pathway, 208/671 (31%) underwent primary microsurgical excision and 23/671 (3.4%) primary radiotherapy. Of patients who entered WWR, 144/440 (32.7%) exhibited tumor growth necessitating secondary intervention at a mean of 22.7 months; 67.4% had radiotherapy and 32.6% surgery. Radiotherapy was successful at achieving tumor control in 95% of cases. Primary surgery via the translabyrinthine route was performed in the majority of cases allowing for a radiologically clear surgical resection in 93% of cases. CONCLUSION: The Cambridge philosophy of treating the newly diagnosed vestibular schwannoma aims at preserving functional status where possible. In patients with small tumors it is recommended that they are placed on to a WWR pathway, of which 67.3% will not exhibit any growth by 5 years. If small tumors grow more than 2 mm by serial scanning, radiotherapy offers a high rate of tumor control. In patients with larger tumors more than 20 mm we would advocate microsurgical excision by the translabyrinthine route which offers excellent functional outcomes and gross tumor control.

Facial Nerve Function Outcome and Risk Factors in Resection of Large Cystic Vestibular Schwannomas.

Objective Cystic vestibular schwannomas (VS) in contrast to solid VS tend to have accelerated growth, larger volume, rapid/atypical presentation, lobulated/adherent surface, and unpredictable course of the cranial nerves. Cystic VS are surgically challenging, with worse clinical outcomes and higher rate of subtotal resection (STR). Methods We retrospectively analyzed postoperative outcomes of 125 patients with cystic VS, operated between years 2005 and 2019 in our center. We confronted the extent of the resection and House-Brackmann (HB) grade of facial palsy with the results of comparable cohort of patients with solid VS operated in our center and literature review by Thakur et al. 1 Results Translabyrinthine approach was preferred for resection of large, cystic VS (97.6%). Gross-total resection (GTR) was achieved in 78 patients (62.4%), near-total resection (NTR) with remnant (<4 × 4 × 2 mm) in 43 patients (34.4%), and STR in 4 patients (3.2%). NTR/STR were significantly associated with higher age, tumor volume >5 cm 3 , retrosigmoid approach, high-riding jugular bulb, tumor adherence to the brain stem, and facial nerve ( p = 0.016; 0.003; 0.005; 0.025; 0.001; and <0.00001, respectively). One year after the surgery, 76% of patients had HB grades 1 to 2, 16% had HB grades 3 to 4, and 8% had HB grades 5 to 6 palsy. Worse outcome (HB grades 3 to 6) was associated with preoperative facial palsy, tumor volume >25 cm 3 , and cyst over the brain stem ( p = 0.045; 0.014; and 0.05, respectively). Comparable solid VS operated in our center had significantly higher HB grades 1 to 2 rate than our cystic VS (94% versus 76%; p = 0.03). Comparing our results with literature review, our HB grades 1 to 2 rate was significantly higher (76% versus 39%; p = 0.0001). Tumor control rate 5 years after surgery was 95.8%. Conclusion Our study confirmed that microsurgery of cystic VS has worse outcomes of facial nerve preservation and extent of resection compared with solid VS. Greater attention should be paid to the above-mentioned risk factors.

Localization of TSH-secreting pituitary adenoma using 11C-methionine image subtraction.

BACKGROUND: Pituitary adenomas (PA) affect ~ 1:1200 of the population and can cause a wide range of symptoms due to hormone over-secretion, loss of normal pituitary gland function and/or compression of visual pathways, resulting in significantly impaired quality of life. Surgery is potentially curative if the location of the adenoma can be determined. However, standard structural (anatomical) imaging, in the form of MRI, is unable to locate all tumors, especially microadenomas (< 1 cm diameter). In such cases, functional imaging [11C-methionine PET/CT (Met-PET)] can facilitate tumor detection, although may be inconclusive when the adenoma is less metabolically active. We, therefore, explored whether subtraction imaging, comparing findings between two Met-PET scans with medical therapy-induced suppression of tumor activity in the intervening period, could increase confidence in adenoma localization. In addition, we assessed whether normalization to a reference region improved consistency of pituitary gland signal in healthy volunteers who underwent two Met-PET scans without medical suppression. RESULTS: We found that the mean percentage differences in maximum pituitary uptake between two Met-PET scans in healthy volunteers were 2.4% for (SUVr) [cerebellum], 8.8% for SUVr [pons], 5.2% for SUVr [gray matter] and 23.1% for the SUVbw [no region]. Laterality, as measured by contrast-noise ratio (CNR), indicated the correct location of the adenoma in all three image types with mean CNR values of 6.2, 8.1 and 11.1 for SUVbw, SUVbwSub and SUVrSub [cerebellum], respectively. Subtraction imaging improved CNR in 60% and 100% of patients when using images generated from SUVbw [no region] and SUVr [cerebellum] scans compared to standard clinical SUVbw imaging. CONCLUSIONS: Met-PET scans should be normalized to the cerebellum to minimize the effects of physiological variation in pituitary gland uptake of 11C-methionine, especially when comparing serial imaging. Subtraction imaging following endocrine suppression of tumor function improved lateralization of PA when compared with single time point clinical Met-PET but, importantly, only if the images were normalized to the cerebellum prior to subtraction.

Evidence-based surveillance protocol for vestibular schwannomas: a long-term analysis of tumor growth using conditional probability.

OBJECTIVE: The growth characteristics of vestibular schwannomas (VSs) under surveillance can be studied using a Bayesian method of growth risk stratification by time after surveillance onset, allowing dynamic evaluations of growth risks. There is no consensus on the optimum surveillance strategy in terms of frequency and duration, particularly for long-term growth risks. In this study, the long-term conditional probability of new VS growth was reported for patients after 5 years of demonstrated nongrowth. This allowed modeling of long-term VS growth risks, the creation of an evidence-based surveillance protocol, and the proposal of a cost-benefit analysis decision aid. METHODS: The authors performed an international multicenter retrospective analysis of prospectively collected databases from five tertiary care referral skull base units. Patients diagnosed with sporadic unilateral VS between 1990 and 2010 who had a minimum of 10 years of surveillance MRI showing VS nongrowth in the first 5 years of follow-up were included in the analysis. Conditional probabilities of growth were calculated according to Bayes' theorem, and nonlinear regression analyses allowed modeling of growth. A cost-benefit analysis was also performed. RESULTS: A total of 354 patients were included in the study. Across the surveillance period from 6 to 10 years postdiagnosis, a total of 12 tumors were seen to grow (3.4%). There was no significant difference in long-term growth risk for intracanalicular versus extracanalicular VSs (p = 0.41). At 6 years, the residual conditional probability of growth from this point onward was seen to be 2.28% (95% CI 0.70%-5.44%); at 7 years, 1.35% (95% CI 0.25%-4.10%); at 8 years, 0.80% (95% CI 0.07%-3.25%); at 9 years, 0.47% (95% CI 0.01%-2.71%); and at 10 years, 0.28% (95% CI 0.00%-2.37%). Modeling determined that the remaining lifetime risk of growth would be less than 1% at 7 years 7 months, less than 0.5% at 8 years 11 months, and less than 0.25% at 10 years 4 months. CONCLUSIONS: This multicenter study evaluates the conditional probability of VS growth in patients with long-term VS surveillance (6-10 years). On the basis of these growth risks, the authors posited a surveillance protocol with imaging at 6 months (t = 0.5), annually for 3 years (t = 1.5, 2.5, 3.5), twice at 2-year intervals (t = 5.5, 7.5), and a final scan after 3 years (t = 10.5). This can be used to better inform patients of their risk of growth at particular points along their surveillance timeline, balancing the risk of missing late growth with the costs of repeated imaging. A cost-benefit analysis decision aid was also proposed to allow units to make their own decisions regarding the cessation of surveillance.

A comparison of CT-based navigation techniques for minimally invasive lumbar pedicle screw placement.

STUDY DESIGN: A comparison of 2 surgical techniques. OBJECTIVE: To determine the relative accuracy of minimally invasive lumbar pedicle screw placement using 2 different CT-based image-guided techniques. SUMMARY OF BACKGROUND: Three-dimensional intraoperative fluoroscopy systems have recently become available that provide the ability to use CT-quality images for navigation during image-guided minimally invasive spinal surgery. However, the cost of this equipment may negate any potential benefit in navigational accuracy. We therefore assess the accuracy of pedicle screw placement using an intraoperative 3-dimensional fluoroscope for guidance compared with a technique using preoperative CT images merged to intraoperative 2-dimensional fluoroscopy. METHODS: Sixty-seven patients undergoing minimally invasive placement of lumbar pedicle screws (296 screws) using a navigated, image-guided technique were studied and the accuracy of pedicle screw placement assessed. Electromyography (EMG) monitoring of lumbar nerve roots was used in all. Group 1: 24 patients in whom a preoperative CT scan was merged with intraoperative 2-dimensional fluoroscopy images on the image-guidance system. Group 2: 43 patients using intraoperative 3-dimensional fluoroscopy images as the source for the image guidance system. The frequencies of pedicle breach and EMG warnings (indicating potentially unsafe screw placement) in each group were recorded. RESULTS: The rate of pedicle screw misplacement was 6.4% in group 1 vs 1.6% in group 2 (P=0.03). There were no cases of neurologic injury from suboptimal placement of screws. Additionally, the incidence of EMG warnings was significantly lower in group 2 (3.7% vs. 10% (P=0.03). CONCLUSIONS: The use of an intraoperative 3-dimensional fluoroscopy system with an image-guidance system results in greater accuracy of pedicle screw placement than the use of preoperative CT scans, although potentially dangerous placement of pedicle screws can be prevented by the use of EMG monitoring of lumbar nerve roots.

BRAF V600E Mutant Lung Adenocarcinoma Presenting With a Skull Base Metastasis and Pituitary Adenoma Collision Tumour.

We report an unusual initial presentation for metastatic lung adenocarcinoma (LAC) with progressive loss of vision, a rare molecular phenotype and rapid visual response to surgical resection. A 60-year-old female presented with rapid and progressive visual loss over four weeks. Contrast-enhanced CT and MRI scans showed an enhancing lobulated mass in the base of skull infiltrating into the sella turcica. The patient underwent transnasal endoscopic debulking of the mass with rapid improvement in her vision. Histology showed a collision tumour with a pituitary adenoma and a microacinar metastatic adenocarcinoma. Staging CT of the chest, abdomen and pelvis showed a T4 N2 M1 right LAC. Molecular profiling of the metastasis confirmed an activating mutation involving codon 600 of BRAF gene (BRAF V600E). The patient was treated with combination chemotherapy but rapidly deteriorated and unfortunately died due to progressive disease. Efforts to access BRAF/MEK inhibitors for off-label use were unsuccessful. We believe our patient would have benefited from a BRAF/MEK inhibitor. This case illustrates the very unusual presentation of metastatic LAC with visual loss secondary to a collision tumour containing a pituitary adenoma and metastatic adenocarcinoma.