Knosp Score Research Articles

Prognostic factors for surgical treatment of prolactin-secreting pituitary adenomas.

Usually, prolactinomas are treated with dopamine agonists (DA). Surgery is considered an option when the patient cannot bear or does not respond positively to DA therapy. This study aims to determine the early and late outcomes of surgery, with particular emphasis on developing prognostic factors for surgical treatment and analyzing risk factors affecting the recurrence of hyperprolactinemia and prolactinoma. This retrospective study was conducted at the Feofaniya Clinical Hospital of the State Administration of Affairs (Kyiv, Ukraine), evaluating 109 patients' records from 2009 to 2019. The main patients' inclusion criteria were: serum prolactin (PRL) level of more than 100 ng/ml, presence of pituitary adenoma (PA) on MRI, histologically approved PA by microscopy. According to the size of the prolactin-secreting PA (PSPAs) the selected 109 patients were divided into two groups: micro- (≤10 mm, n = 75) and macroadenoma group (10-40 mm, n = 34). 1 month after the operation, PRL levels decreased by 87% (p < 0.001), 12 months-by 93% (p < 0.001). After receiving surgery and DA therapy for 12 months 77.1% of patients achieved biochemical remission. Out of the total number of patients observed, 15.6% (n = 17) had a Knosp score greater than 3. Additionally, in the macroadenoma group, the percentage of patients with a Knosp score greater than 3 was 41,2%, which was significantly higher as compared to the microadenoma group (4%, p < 0.001). In patients with microadenomas a weak reverse correlation between patients' age (r = -0.258, p < 0.026) and positive with tumor size (r = 0.251, p < 0.030) was revealed. In the macroadenoma group significant association was found only between preoperative serum PRL level and tumor size (r = 0.412, p < 0.016). The preoperative PRL can be used as a diagnostic marker for lack of early biochemical remission in patients with PSPAs with diagnostic accuracy 66.9%. This study found that primary transsphenoidal surgery is an effective treatment in reaching PRL level control in patients with both micro- and macroprolactinomas. The correct and thorough selection of candidates for surgery is crucial to achieve postoperative serum PRL normalization in the vast majority of patients.

Experimental Comparison of a Rule-Based Approach and Deep Learning to Automatically Assess Knosp Score for Pituitary Adenomas

Experimental Comparison of a Rule-Based Approach and Deep Learning to Automatically Assess Knosp Score for Pituitary Adenomas

A Multicenter, Propensity Score-Matched Assessment of Endoscopic Versus Microscopic Approaches in the Management of Pituitary Adenomas.

There is considerable controversy as to which of the 2 operating modalities (microsurgical or endoscopic transnasal surgery) currently used to resect pituitary adenomas (PAs) is the safest and most effective intervention. We compared rates of clinical outcomes of patients with PAs who underwent resection by either microsurgical or endoscopic transnasal surgery. To independently assess the outcomes of each modality type, we sought to isolate endoscopic and microscopic PA surgeries with a 1:1 tight-caliper (0.01) propensity score-matched analysis using a multicenter, neurosurgery-specific database. Surgeries were performed between 2017 and 2020, with data collected retrospectively from 12 international institutions on 4 continents. Matching was based on age, previous neurological deficit, American Society of Anesthesiologists (ASA) score, tumor functionality, tumor size, and Knosp score. Univariate and multivariate analyses were performed. Among a pool of 2826 patients, propensity score matching resulted in 600 patients from 9 surgery centers being analyzed. Multivariate analysis showed that microscopic surgery had a 1.91 odds ratio (OR) ( P = .03) of gross total resection (GTR) and shorter operative duration ( P < .01). However, microscopic surgery also had a 7.82 OR ( P < .01) for intensive care unit stay, 2.08 OR ( P < .01) for intraoperative cerebrospinal fluid (CSF) leak, 2.47 OR ( P = .02) for postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was an independent predictor for longer postoperative stay (β = 2.01, P < .01). Overall, no differences in postoperative complications or 3- to 6-month outcomes were seen by surgical approach. Our international, multicenter matched analysis suggests microscopic approaches for pituitary tumor resection may offer better GTR rates, albeit with increased intensive care unit stay, CSF leak, SIADH, and hospital utilization. Better prospective studies can further validate these findings as matching patients for outcome analysis remains challenging. These results may provide insight into surgical benchmarks at different centers, offer room for further registry studies, and identify best practices.

Endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: Learning curve and surgical results in a prospective series during initial experience.

BackgroundTo report the initial experience of surgery for non-functioning pituitary adenoma (NFPA) from a neurosurgeon in a dedicated residency training endoscopic transsphenoidal (ETS) program, and detail the surgical and clinical outcomes during this period.MethodsA prospective series of all patients operated for NFPA, using an ETS approach, during the three first years of experience of a newly board-certified neurosurgeon was analysed. Clinical, radiological and peri-operative data were collected. Extent of resection (EOR) was determined by formal volumetric analysis. Impact of the learning curve and predictive factors of gross total resection (GTR) were determined.ResultsFifty-three patients with NFPA were included in this prospective cohort which was divided in two periods of time (“First period”: 30 first cases, and “second period”: 23 following cases). Baseline characteristics of the patients in the two periods were similar. Overall occurrence of complication was 22% and was not significantly different in the two periods of time. No patient had severe neurological complication. Gross total resection was achieved in 70% of patients. Mean Extent of resection was 96%. In a multiple linear regression model, a higher EOR was positively correlated with experience (p = 0.018) and negatively correlated with Knosp Score equal to 4 (p < 0.001). Predictive factors for GTR were Higher Knosp grade (p = 0,01), higher pre-operative volume (p = 0.03), and second period of time (p = 0.01).ConclusionNFPA surgery can be safe and efficient during the learning period. Dedicated intensive learning, careful patient selection and multidisciplinary work are key to shorten the learning curve and achieve satisfactory results.

The role of endoscopic endonasal surgery in the management of prolactinomas based on their invasiveness into the cavernous sinus.

To review our institutional experience with thesurgical management of prolactinomas through the endoscopic endonasal approach with specific focus on cavernous sinus invasion. Clinical and radiographic data were collected retrospectively from the electronic medical record of 78 consecutive patients with prolactinomas undergoing endoscopic endonasal resection from 2002 to 2019. Immediate and late post-operative remission were defined as prolactin < 20ng/mL within 14days and 1-year of surgery without adjuvant therapy, respectively. Cavernous sinus invasion was quantified by Knosp score. A total of 78 patients with prolactinoma, 59% being male, underwent surgical resection with a mean age of 37 ± 13years. Indications for surgery were medication resistance in 38 patients (48.7%), medication intolerance in 11 (14.1%), and patient preference in 29 (37.2%). Patients with Knosp 0-2 achieved higher immediate remission rates (83.8%) compared to patients with Knosp 3 (58.8%) and Knosp 4 (41.7%) patients (p = 0.003). Long-term remission rates were 48.7% and increased to 71.8% when combined with adjuvant treatments. Knosp 4 prolactinomas had significantly higher tumor volumes, higher preoperative prolactin levels, higher recurrence rates, higher rates of adjuvant therapy utilization, and were more likely to have failed dopamine agonist therapy compared to other tumor grades (p < 0.05). We encountered 18 complications in our series, and no cerebrospinal fluid leaks. The endoscopic endonasal approach is a safe and effective modality that can be employed in properly selected patients with invasive prolactinomas. It is associatedwith improved control and remission rates despite cavernous sinus invasion, though at a lower rate than without invasion.

Evaluation of Pure Endoscopic Endonasal Approach in Management of Giant Pituitary Adenoma

Abstract Background Giant pituitary adenoma represents one of the challenging tumor for neurosurgeons. Many microsurgical approaches in the past were used for its management. Recently and with evolution of the endoscopic equipment and instruments, extended endoscopic transsphenoidal approach become one of the preferable approaches for its surgical excision. Methods We prospectively document the clinical , surgical and follow up data for all patients presented with giant pituitary adenoma to Ain-Shams university hospital and Weill Cornell Medical College, Presbyterian hospital and were surgically treated with extended transsphenoidal approach from 2015 till 2019. Results Our group study formed of 44 patients with mean age 53.03 (range 14.7-82.4) and a male predominance (59%). The main presentation was visual problems in 75% followed by partial hypopituitarism in 31.81% while headache was in 13.64%. Only 4 patients had functioning adenoma (3 prolactinoma and 1 acromegaly). Average tumor volume was 26.95 ± 17.25 cm3, while the mean maximum tumor diameter was 4.73 cm (range 4.0-8.0 cm). Radiographic invasion was found in 97.73% to suprasellar cistern, 61.36% to the cavernous sinus and in 34% to the sphenoid sinus. GTR was achieved in 45.45% with Knosp score is the only significant predictor factor for resection rate (p = 0.04). Visual improvement achieved in 75.76%. 50% (2 patient) of the patients with functioning adenoma were cured. Complications included CSF leak in 3 patients, permanent DI in 4 patients and postoperative hematoma in 2 patients. Recurrence and progression rates without upfront radiation therapy were 5.00 % and 31.81% respectively after mean follow up period 57.90 months. Conclusions Extended endoscopic approaches for achieving maximum resection with minimal morbidity for giant pituitary adenoma are very effective. Lateral tumor extension with cavernous sinus invasion represents the limiting point in achieving gross total resection. Upfront radiation therapy for patients with residual adenoma can be avoided but regular follow up should be warranted.

Predictors of postoperative biochemical remission in acromegaly.

Acromegaly is a rare neuroendocrine condition that can lead to significant morbidity. Despite China's vast population size, studies on acromegaly remain sparse. This study aimed to investigate the clinical characteristics and predictors of biochemical remission after surgery for acromegaly using the China Acromegaly Patient Association (CAPA) database. A retrospective nationwide study was conducted using patient-reported data from CAPA database between 1998 and 2018. The principal component analysis (PCA) and logistic regression analysis were employed to determine independent predictors of biochemical remission at 3months in patients after surgery. Of the 546 surgical cases (mean age: 36.8years; 59.5% females), macroadenomas and invasive tumors (Knosp score 3-4) were 83.9% and 64.1%, respectively. Ninety-five percent of patients were treated with endonasal surgery and 36.8% exhibited biochemical remission at 3-months postoperatively. The following independent predictors of biochemical remission were identified: preoperative growth hormone (GH) levels between 12 and 28μg/L [odds ratio (OR) = 0.58; 95% confidence interval (CI), 0.37-0.92; p = 0.021], preoperative GH levels > 28μg/L (OR = 0.55; 95% CI, 0.34-0.88; p = 0.013), macroadenoma (OR = 0.56; 95% CI, 0.32-0.96; p = 0.034), giant adenomas (OR = 0.14; 95% CI, 0.05-0.38; p < 0.001), Knosp score 3-4 (OR = 0.37; 95% CI, 0.24-0.57; p < 0.001), and preoperative medication usage (OR = 2.32; 95% CI, 1.46-3.70; p < 0.001). In this nationwide study spanning over two decades, we highlight that higher preoperative GH levels, large tumor size, and greater extent of tumor invasiveness are associated with a lower likelihood of biochemical remission at 3-months after surgery, while preoperative medical therapy increases the chance of remission.

Impact of tumor characteristics and pre- and postoperative hormone levels on hormonal remission following endoscopic transsphenoidal surgery in patients with acromegaly.

Acromegaly is a disease of acral enlargement and elevated serum levels of insulin-like growth factor-1 (IGF-1) and growth hormone (GH), usually caused by a pituitary adenoma. A lack of consensus on factors that reliably predict outcomes in acromegalic patients following endoscopic endonasal transsphenoidal surgery (EETS) warrants additional investigation. The authors identified 52 patients with acromegaly who underwent an endoscopic endonasal approach (EEA) for resection of a GH-secreting pituitary adenoma. Preoperative and postoperative tumor and endocrinological characteristics such as tumor size, invasiveness, and GH/IGF-1 levels were evaluated as potential indicators of postoperative hormonal remission. Endocrinological remission was defined as postoperative IGF-1 levels at or below the age- and sex-normalized values. The 52 patients had a mean age of 50.7 ± 13.4 years and a mean follow-up duration of 24.4 ± 19.1 months. Ten patients (19%) had microadenomas and 42 (81%) had macroadenomas. Five patients (9.6%) had giant adenomas. Forty-four tumors (85%) had extrasellar extension, with 40 (77%) exhibiting infrasellar invasion, 18 (35%) extending above the sella, and 7 (13%) invading the cavernous sinuses. Thirty-six patients (69%) underwent gross-total resection (GTR; mean maximal tumor diameter 1.47 cm), and 16 (31%) underwent subtotal resection (STR; mean maximal tumor diameter 2.74 cm). Invasive tumors were significantly larger, and Knosp scores were negatively correlated with GTR. Thirty-eight patients (73%) achieved hormonal remission after EEA resection alone, which increased to 87% with adjunctive medical therapy. Ninety percent of patients with microadenomas and 86% of patients with macroadenomas achieved hormonal remission. Preoperative IGF-1 and postoperative day 1 (POD1) GH levels were inversely correlated with hormonal remission. Postoperative CSF leakage occurred in 2 patients (4%), and none experienced vision loss, death, or injury to internal carotid arteries or cranial nerves. Endoscopic transsphenoidal resection of GH-secreting pituitary adenomas is a safe and highly effective treatment for achieving hormonal remission and tumor control in up to 87% of patients with acromegaly when combined with postoperative medical therapy. Patients with lower preoperative IGF-1 and POD1 GH levels, with less invasive pituitary adenomas, and who undergo GTR are more likely to achieve postoperative biochemical remission.

MON-319 Impact of Tumor Characteristics and Preoperative IGF-1 Levels on Postoperative Hormonal Remission Following Endoscopic Transsphenoidal Surgery in Patients with Acromegaly: A Single-Surgeon Series

Introduction:Acromegaly is a potentially fatal neuro-endocrinopathy caused by a growth hormone (GH)-secreting pituitary adenoma (PA). A lack of consensus on factors that reliably predict patient outcomes in acromegalic patients following endoscopic endonasal approaches (EEA) warrants additional investigation.Methods:Pre- and postoperative tumor and endocrinological characteristics from 55 acromegalic patients who underwent EEA for resection of a GH-secreting PA were evaluated as potential predictors of postoperative hormonal remission (defined as age- and sex- normalized IGF-1 levels).Results:The 55 patients included had a mean age of 50.1 ± 13.5 years and a mean follow-up time of 18 ± 17.4 months. Fifty-three patients (96%) presented with dysmorphic craniofacial features, with 22 (40%) presenting with prognathism, 22 (40%) exhibiting frontal bossing, and 18 (33%) presenting with macroglossia. Ten (18%) had microadenomas and 45 (82%) had macroadenomas. Five (9.4%) had giant adenomas. Forty-five (92%) tumors were invasive, with 44 (83%) exhibiting infrasellar invasion, 17 (32%) extending above the sella, and 9 (18%) with cavernous sinus invasion. Thirty-three patients (66%) underwent gross total resection (GTR; mean maximal tumor diameter = 1.52 cm), and 17 (34%) underwent subtotal resection (STR; mean maximal tumor diameter = 2.77 cm). Invasive tumors were significantly larger and Knosp scores were negatively correlated with GTR. Thirty-three patients (65%) achieved hormonal remission after EEA resection alone, which increased to 80% with adjunctive medical therapy. Additionally, 90% of patients who underwent GTR and 63% of patients who underwent STR demonstrated postoperative remission. Six patients (11%) exhibited biochemical remission after postoperative medical therapy with an average time to remission of 5.2 months. These patients all had significantly higher preoperative IGF-1 levels and larger tumors than patients who remitted immediately postoperatively. In all patients preoperative IGF-1 levels were inversely correlated with hormonal remission.Conclusions:This study indicates that endoscopic transsphenoidal resection of growth hormone secreting pituitary adenomas is a safe and highly effective management strategy for achieving hormonal remission and tumor control for patients with acromegaly. When combined with postoperative medical therapy, we observed endocrinological remission rates of 80% based on normalized IGF-1 levels. Our results support the conclusions of current literature that smaller and less invasive tumors are more likely to be fully resected. We additionally suggest that patients with lower preoperative IGF-1 are more likely to undergo postoperative biochemical remission, irrespective of tumor size and invasion.

Long-term outcomes after endoscopic endonasal surgery for nonfunctioning pituitary macroadenomas.

Nonfunctioning pituitary adenomas are benign, slow-growing tumors. After gross-total resection (GTR) or subtotal resection (STR), tumors can recur or progress and may ultimately require additional intervention. A greater understanding of long-term recurrence and progression rates following complete or partial resection and the need for further intervention will help clinicians provide meaningful counsel for their patients and assist data-driven decision-making. The authors retrospectively analyzed their institutional database for patients undergoing endoscopic endonasal surgery (EES) for nonfunctioning pituitary macroadenomas (2003-2014). Only patients with follow-up of at least 5 years after surgery were included. Tumor volumes were measured on pre- and postoperative MRI. Tumor recurrence was defined as the presence of a 0.1-cm3 tumor volume after GTR, and tumor progression was defined as a 25.0% increase in residual tumor after STR. A total of 190 patients were included, with a mean age of 63.8 ± 13.2 years; 79 (41.6%) were female. The mean follow-up was 75.0 ± 18.0 months. GTR was achieved in 127 (66.8%) patients. In multivariate analysis, age (p = 0.04), preoperative tumor volume (p = 0.03), Knosp score (p < 0.001), and Ki-67 (p = 0.03) were significant predictors of STR. In patients with GTR, the probability of recurrence at 5 and 10 years was 3.9% and 4.7%, and the probability of requiring treatment for recurrence was 0.79% and 1.6%, respectively. In 63 patients who underwent STR, 6 (9.5%) received early postoperative radiation and did not experience progression, while the remaining 57 (90.5%) were observed. Of these, the probability of disease progression at 5 and 10 years was 21% and 24.5%, respectively, and the probability of requiring additional treatment for progression was 17.5% and 21%. Predictors of recurrence or progression in the entire group were Knosp score (p < 0.001) and elevated Ki-67 (p = 0.03). Significant predictors of progression after STR in those who did not receive early radiotherapy were cavernous sinus location (p < 0.05) and tumor size > 1.0 cm3 (p = 0.005). Following GTR for nonfunctioning pituitary adenomas, the 10-year chance of recurrence is low and the need for treatment even lower. After STR, although upfront radiation therapy may prevent progression, even without radiotherapy, the need for intervention at 10 years is only approximately 20% and a period of observation may be warranted to prevent unnecessary prophylactic radiation therapy. Tumor volume > 1 cm3, Knosp score ≥ 3, and Ki-67 ≥ 3% may be useful metrics to prompt closer follow-up or justify early prophylactic radiation therapy.

Tumor T2 signal intensity and stalk angulation correlates with endocrine status in pituitary adenoma patients: a quantitative 7tesla MRI study.

Pituitary adenomas are common CNS tumors that can cause endocrine dysfunction due to hormone oversecretion and by mass effect on the normal gland. The study of pituitary adenomas and adjacent sellar anatomy with high-resolution 7T MRI may further characterize endocrine dysfunction. The purpose of this study was to determine the efficacy of 7T MRI in identifying radiological markers for endocrine function. MR images obtained in 23 patients with pituitary adenomas were reviewed by consensus between three neuroradiologists. Landmarks and criteria were devised to measure radiological features of stalk, tumor, and normal gland. Fischer's exact tests and nominal logistic regression were performed. Mean cross-sectional area of the stalk just below the infundibular recess was 6.3 ± 3.7mm2. Mean curvature and deviation angles were 34.2° ± 23.2° and 29.7° ± 17.3°, respectively. Knosp scores obtained differed between 7T and lower field strength scans (P < 0.0001 [right] and P = 0.0006 [left]). Ability to characterize tumor was rated higher at 7T compared with lower field MRI, P = 0.05. Confidence in visualizing normal gland was also higher using 7T MRI, P = 0.036. The six hormone-secreting tumors had higher corrected T2 mean SI than non-secreting tumors (2.54 vs. -0.38, P = 0.0196). Seven patients had preoperative hypopituitarism and had significantly greater stalk curvature angles than patients without hypopituitarism (71.7° vs. 36.55°, P = 0.027). Radiological characterization of pituitary adenomas and adjacent native pituitary tissue may benefit with the use of 7T MRI. Corrected T2 SI of tumor may be a sensitive predictor of hormonal secretion and may be useful in the diagnostic work-up for pituitary adenoma. 7T MRI may be valuable in identifying markers of endocrine function in patients with pituitary adenomas. Our results indicate that hormone-secreting tumors have higher T2-weighted SI and tumors associated with preoperative hypopituitarism have greater stalk curvature angles.

Surgical Outcome of Endoscopic Endonasal Surgery of Large and Giant Pituitary Adenomas: An Institutional Experience from the Middle East

Surgical treatment of large and giant pituitary adenomas is challenging and associated with higher risk of complications and lower rate of gross total resection. We present our experience with surgical management of large and giant adenomas using the extended endoscopic transsphenoidal approach (EETA). A total of 80 patients with large (30-39 mm) and giant (≥40 mm) pituitary adenomas who underwent tumor resection using EETA were studied. Radiologic data, hormonal and visual status, surgical outcomes, complications, and factors affecting the extent of resection were evaluated. Forty-five tumors (56.3%) were classified as large and 35 (43.8%) as giant adenomas. Gross total resection was achieved in 66 patients (82.5%), near-total resection in 10 (12.5%), and subtotal resection in 4 (5%). Preoperative factors including larger tumor size, multilobular shape of tumor, and higher Knosp scores significantly decrease the likelihood of gross total resection. Of patients with preoperative visual acuity impairment and visual field deficit, 76.8% and 74.1%, respectively, experienced improvement after surgery. The most common complications include new pituitary insufficiency (16.4%), permanent diabetes insipidus (7.5%), and cerebrospinal fluid leakage (5%). Two cases of meningitis (2.5%) and 3 deaths (3.8%) occurred in this cohort of patients. Mean follow-up duration was 24.2 months. EETA can be a safe and efficient approach as the first-line treatment of patients with large and giant pituitary adenomas and is associated with high rates of gross total resection or near-total resection, visual function improvement, and a relatively low rate of complications.

High-Field Intraoperative Magnetic Resonance Imaging Increases Extent of Resection and Progression-Free Survival for Nonfunctioning Pituitary Adenomas

The effect of intraoperative magnetic resonance imaging (iMRI) on tumor control during endoscopic transsphenoidal surgery (TSS) for nonfunctioning pituitary adenomas (NFPAs) has not yet been completely characterized. The present study assessed the effect of the iMRI findings on gross total resection (GTR) and progression-free survival at a mean follow-up of 62 ± 9.4 months. Retrospective analyses were performed on the data from 133 consecutive patients with NFPA who had undergone endoscopic TSS with iMRI using a 1.5T scanner. Compared with the first and final iMRI scans, the GTR rate increased from 42.9% to 63.9%. Multivariate logistic regression analysis revealed that a lower GTR rate was associated with a higher Knosp score (odds ratio [OR], 3.612; 95% confidence interval [CI], 1.568-8.321; P= 0.003), an increased tumor volume (OR, 0.926; 95% CI, 0.866-0.991; P= 0.025), and a history of surgery (OR, 0.376; 95% CI, 0.155-0.917; P= 0.031). During follow-up, 8 tumors (9.4%) recurred, and 29 remnants (60.4%) regenerated. The recurrence and regeneration rates were 0.019 and 0.121 patient/year, respectively. Kaplan-Meier analysis revealed that the tumor recurrence rates were lower for patients who had undergone GTR (P < 0.01) compared with those who had not. Univariate Cox regression analysis suggested that the presence of tumor remnants (hazard ratio, 1.546; 95% CI, 1.071-2.232; P= 0.02) was the influencing factor associated with tumor progression. High-field iMRI can increase the GTR rate in endoscopic TSS for NPFAs. The increased GTR rate was associated with longer progression-free survival. Cavernous sinus invasion, tumor size, and surgical history were important predictors of GTR in patients with NFPA.

Pre-operative MRI predictors of hormonal remission status post pituitary adenoma resection

IntroductionContrast-enhanced (CE) Constructive Interference in Steady State (CISS) and Volumetric Interpolated Breath-hold Examination (VIBE) are MRI sequences used to improve the detection of pituitary adenomas and adjacent cranial nerves. The purpose of this study was to assess image quality and identify imaging predictors of postoperative hormonal remission of functioning pituitary adenomas using CE-T1 weighted image (WI), T2WI, CE-CISS, and CE-VIBE MRI sequences. Materials and methodsPatients with pre-operative CE-T1WI, T2WI, CE-CISS, and CE-VIBE pituitary MRI sequences were included in this institutional retrospective review. Three raters independently reviewed randomized sequences in a blinded fashion for adenoma characteristics and parasellar invasion. Subgroup analysis of hormonal remission was performed. ResultsA total of 34 functioning pituitary adenoma patients were included (average age 39.3 ± 12.2; female n = 27), 30 of which had post-operative hormonal remission (n = 34; 88.2%). Compared to CE-T1WI, CE-CISS has significantly higher number of sequences rated “good” image quality (p = 0.02). Hormone remission was associated with decreased degrees of pre-operative internal carotid artery (ICA) contact and Knosp score (p ≤ 0.02) on all sequences except for Knosp score on T2WI. On receiver operating characteristic analysis, the area under curve for differentiating endocrine remission ranged from 0.88 to 0.92 for Knosp score and 0.85–0.93 for ICA contact, depending on sequence. ConclusionExtent of pituitary adenoma cavernous sinus invasion as measured by degrees of ICA contact and Knosp score is associated with postoperative endocrine outcomes. Given improved image quality, inclusion of CE-CISS may be helpful for pre-surgical planning.

Endoscopic Transsphenoidal Approach for Surgical Treatment of Growth Hormone Secreting Pituitary Adenoma: Endocrinological Outcome in 49 Patients Based on 2010 Consensus Criteria for Remission - Preliminary Result

Background: Nowadays, the endoscopic transsphenoidal approach is the initial option for resection of all pituitary adenomas. The current study reported the experience with endoscopic transsphenoidal surgery remission rates using the 2010 consensus criteria, predictors of remission, and the associated complications. Methods: A prospectively collected database of 49 patients with acromegaly who underwent endoscopic endonasal transsphenoidal surgery was analyzed. Tumors were classified according to size, as well as the Knosp and the Hardy-Wilson classifications. Endocrinological remission was defined as normal insulin-like growth factor (IGF)-I level and either a suppressed growth hormone (GH) level < 0.4 ng/mL during an oral glucose tolerance test, or a random GH level < 1.0 ng/mL at least 3 months after the surgery. The extent of resection was evaluated on postoperative contrast-enhanced magnetic resonance imaging (MRI). Results: Biochemical remission was achieved in 7 of 9 (77.8%) microadenoma and 28 of 40 (70%) macroadenoma. The total remission rate was 71.4% and gross total resection was achieved in 45 of 49 (91.8%) patients. Tumor size, age, gender, history of prior surgery, suprasellar extension, and sphenoid sinus invasion were not associated with remission rate. Preoperative variables predictive of remission included the Knosp score (P = 0.041) and GH levels (P = 0.047). Two patients (4.1%) experienced postoperative pan hypopituitarism, and permanent DI was observed in 3 (6.1%) patients. One patient (2%) had cerebrospinal fluid (CSF) leaks treated with serial lumbar punctures. The median follow-up period was 25.45 months; ranged from 3 to 49. Conclusions: Endoscopic transsphenoidal adenoma resection leads to a high rate of endocrinological remission in patients with low acromegaly complication. Patients with high preoperative GH levels and the Knosp scores are less likely to achieve remission.

Endoscopic endonasal transsphenoidal surgery for giant pituitary adenomas: a report of 69 cases

Objective To present our experience with the surgical management of giant pituitary adenomas through endoscopic endonasal transsphenoidal approach. Methods A retrospective data analysis of all patients who underwent endoscopic endonasal transsphenoidal surgery in Nanfang Hospital between January 2007 and June 2013 was performed. Patients who presented with pituitary adenomas larger than 4 cm were included in the study. Analysis of factors related to the choice of the operative approach, extent of resection, follow-up outcome, and complications were evaluated. Results Sixty-nine patients (18%) with giant adenomas matched our inclusion criteria. This included 51 (74%) patients with nonfunctional tumors, 11 (16%) prolactinomas, and 7 (10%) growth hormone-secreting adenomas. Gross total removal of the tumor was achieved in 26 cases (38%), subtotal removal in 23 (33%), and 20 (29%) had partial resection. Postoperative diabetes insipidus occurred in 9 cases (13%), new anterior pituitary insufficiency in 10 (15%), CSF leaks in 2 (3%), and meningitis in 2(3%). There was no dead case. The patients with Knosp score 3-4 adenomas had a higher total resection rate than those with Knosp score 0-2 (P< 0.001). Preoperative headache, visual dysfunction, oculomotor disorders and hypopituitarism were recovered in 20(83%), 59(86%), 9(60%), and 12(36%) cases, respectively. Nine patients with nonfunctional tumors underwent a second transsphenoidal surgery, 10 underwent radiotherapy, and 14 had a follow-up care. Drug therapy was performed in 11 patients with functional tumors, and radiotherapy in 3. Conclusions Endoscopic endonasal surgery might provide safe and effective treatment for patients with giant adenomas. The selection of surgical approach should be established according to the tumor extension and personal experience. In cases in which total resection might be associated with high risk, we advocated the use of partial resection followed by adjuvant drug therapy or radiotherapy. In cases of progressive enlargement of residual lesions, a second endoscopic procedure or radiotherapy might be considered. Key words: Endoscopy; Giant pituitary adenomas; Transsphenoidal surgery

Gremlin, a bone morphogenetic protein antagonist, is a crucial angiogenic factor in pituitary adenoma.

Gremlin is an antagonist of bone morphogenetic protein (BMP) and a major driving force in skeletal modeling in the fetal stage. Several recent reports have shown that Gremlin is also involved in angiogenesis of lung cancer and diabetic retinopathy. The purpose of this study was to investigate the role of Gremlin in tumor angiogenesis in pituitary adenoma. Double fluorescence immunohistochemistry of Gremlin and CD34 was performed in pituitary adenoma tissues obtained during transsphenoidal surgery in 45 cases (7 PRLoma, 17 GHoma, 2 ACTHoma, and 2 TSHoma). Gremlin and microvascular density (MVD) were detected by double-immunofluorescence microscopy in CD34-positive vessels from tissue microarray analysis of 60 cases of pituitary adenomas (6 PRLoma, 23 GHoma, 22 NFoma, 5 ACTHoma, and 4 TSHoma). In tissue microarray analysis, MVD was significantly correlated with an increased Gremlin level (linear regression: P < 0.005, r 2 = 0.4958). In contrast, Gremlin expression showed no correlation with tumor subtype or Knosp score. The high level of expression of Gremlin in pituitary adenoma tissue with many CD34-positive vessels and the strong coherence of these regions indicate that Gremlin is associated with angiogenesis in pituitary adenoma cells.

Long-term results of endonasal endoscopic transsphenoidal resection of nonfunctioning pituitary macroadenomas.

Several studies report early results of endoscopic endonasal transsphenoidal surgery; however, none discuss long-term outcome measures such as tumor recurrence rates and the need for additional surgical procedures. To discuss the long-term outcomes after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary macroadenomas. This is a retrospective study. Patients were included only if they had at least 5 years of clinical and imaging follow-up after surgery. Eighty patients met the study criteria. Grossly complete resection was achieved in 71% of patients. Knosp grade 0 to 2 tumors and tumor with volumes <10 cm were significantly more likely to have received a grossly complete resection. There were 7 recurrences (12%) in patients who had received grossly complete resections, with a mean time to recurrence of 53 months. Among the 23 patients who had subtotal resections, 11 (61%) progressed radiographically, and 3 (17%) had symptomatic progression. Knosp score, surgical and radiographic evidence of invasion, and preoperative visual deficits were predictive of recurrence in a univariate analysis, but Knosp grade was the only independent predictor in a multivariate analysis. Kaplan-Meier analysis projected a 10-year progression-free survival rate of 80% and 21% for patients with gross total resections and subtotal resections, respectively. At the long-term follow-up, 12% of patients had recurrent tumors after grossly complete resection. Recurrent or residual tumors were treated with either repeat surgery or Gamma Knife radiosurgery. Rates of complete resection, postoperative surgical and endocrinological complications, and additional surgical procedures are similar to previously published reports after microscopic transsphenoidal surgery.

Endoscopic Endonasal Transsphenoidal Pituitary Surgery: Experience of 80 Cases.

Surgical approaches to the pituitary have undergone numerous refinements over the last 100 years. The fully endoscopic transsphenoidal approach has gained widespread use all around the world. We report the results of a consecutive series of patients who underwent pituitary surgery using a pure endoscopic endonasal approach and the results of the evaluation of the efficacy and safety of this procedure. We retrospectively reviewed the hospital database of 80 consecutive pituitary adenomas that were resected with the purely endoscopic endonasal transsphenoidal technique. The preoperative clinical condition of the patients, hormone profile, visual field, computed tomography and magnetic resonance imaging findings, and the Hardy-Vezina and Knosp scores were evaluated and revealed the importance of the parameters for surgery. Surgical technique, postoperative clinical condition of the patients, hormone profile, complications and follow-up period were reviewed. Endonasal endoscopic pituitary surgery is a safe and effective surgical technique.

Endoscopic vs Microsurgical Transsphenoidal Surgery for Acromegaly: Outcomes in a Concurrent Series of Patients Using Modern Criteria For Remission

It is unclear whether endoscopic transsphenoidal surgery (ETSS) or microsurgical transsphenoidal surgery (MTS) is a superior surgical approach for pituitary adenomas. The objective of the study was to compare the outcome of surgery with ETSS and MTS by experienced pituitary surgeons using criteria of remission using current consensus criteria for acromegaly. This was a retrospective review of prospectively recorded outcomes. The study was conducted at a tertiary referral center. Patients, Interventions, and Outcome Measures: Remission was defined as a normal IGF-I level and either suppressed GH less than 0.4 ng/mL during an oral glucose tolerance test or random GH less than 1.0 ng/mL. The Youden indices were calculated to determine the optimal cutoffs for using immediate postoperative GH levels to predict the results of later testing for remission. Preoperative demographics and tumor characteristics were not significantly different between patients undergoing ETSS (72 patients) or MTS (41 patients). Overall, postoperative remission was achieved in 20 of 23 microadenomas (87%) and 59 of 90 macroadenomas (66%). Remission rates and perioperative complications were not significantly different between ETSS and MTS groups, except for self-reported sinusitis and alterations in taste or smell, which were significantly higher in patients treated with ETSS. Preoperative variables predicting remission in multivariate analysis included GH less than 45 ng/mL [odds ratio (OR) 6.4, P = .010)] and Knosp score of 0-2 (OR 6.8, P < .001). Postoperative in-hospital GH less than 1.15 ng/mL provided the best predictor of remission (OR 7.7, P < .001; sensitivity of 73%, specificity of 85%) defined by follow-up testing. Outcomes of transsphenoidal surgery for acromegaly by experienced pituitary surgeons do not differ between endoscopic and microscopic techniques. Regardless of the mode of resection, patients with high preoperative GH levels and Knosp scores are less likely to achieve remission. An immediate postoperative GH level of less than 1.15 ng/mL provides the best immediate predictor of remission, but long-term outcomes are indicated.