Outcome of Transsphenoidal Surgery for Cushing Disease

Cushing's disease

Neurosurgery 78:216–223, 2016

Transsphenoidal surgery is the standard approach for treating Cushing disease. Evidence is needed to document effectiveness.

OBJECTIVE: To analyze results of transsphenoidal surgery in 276 consecutive patients, including 19 children.

METHODS: Medical records were reviewed for patients treated initially with surgery for Cushing disease from 1980 to 2012. Radiographic features, pathology, remissions, recurrences, and complications were recorded. Patients were categorized for statistical analysis based on tumor size (microadenomas, macroadenomas, and negative imaging) and remission type (type 1 = morning cortisol ≤3 mg/dL; type 2 = morning cortisol normal).

RESULTS: Females comprised 78% of patients and were older than men. Imaging showed 50% microadenomas, 13% macroadenomas, and 37% negative for tumor. Remission rates for microadenomas, macroadenomas, and negative imaging were 89%, 66%, and 71%, respectively. Patients with microadenomas were more likely to have type 1 remission. Pathology showed adrenocorticotropic hormone-secreting adenomas in 82% of microadenomas, in 100% of macroadenomas, and in 43% of negative imaging. The incidence of hyperplasia was 8%. The finding of hyperplasia or no tumor on pathology predicted treatment failure. The recurrence rate was 17%, with an average time to recurrence of 4.0 years. Patients with type 1 remission had a lower rate of recurrence (13% type 1 vs 50% type 2) and a longer time to recurrence. Children had similar imaging findings, remission rates, and pathology. There were no operative deaths.

CONCLUSION: Transsphenoidal surgery provides a safe and effective treatment for Cushing disease. For both adults and children, the best outcomes occurred in patients with microadenomas and/or those with type 1 remission.

Pure endoscopic transsphenoidal surgery for functional pituitary adenomas: outcomes with Cushing’s disease

Cushing's disease

This study was performed to examine patient outcomes following pure endoscopic transsphenoidal surgery (ETS) for Cushing’s disease (CD).

Method We studied 64 consecutive patients who underwent 69 endoscopic transsphenoidal procedures. Radiological evaluation comprised detailed examination of preoperative magnetic resonance images (MRI), including positron emission tomography (PET) for select cases. Inferior petrosal sinus sampling (IPSS) was not performed for any patient. Remission was defined by the presence of hypocortisolemia with requirement for steroid replacement therapy or eucortisolemia with suppression to <1.8 μg/dl after 1 mg dexamethasone on evaluation at least 3 months after surgery.

Results Preoperative MRI was abnormal in 87.5 % of cases and included 11 macroadenomas (17.2 %). PET was used to localize the adenoma in four cases. For microadenomas, operative procedures executed were as follows: selective adenomectomy (n=15), enlarged adenomectomy (n=21) and subtotal/hemihypophysectomy (n=17). Overall, pathological confirmation of an adenoma was possible in 58 patients (90.6 %). Forty-nine patients (76.6 %) developed hypocortisolemia (<5 μg/dl) in the early postoperative period. Mean follow-up was 20 months (range 6–18 months). Remission was confirmed in 79.7 % of the 59 cases followed up for >3 months and was superior for microadenomas (86.4 %) versus macroadenomas (55.6 %) and equivocal MRI adenomas (66.7 %). Postoperative CSF rhinorrhea occurred in five patients, and new endocrine deficits were noted in 17.1 % patients. A nadir postoperative cortisol <2 μg/dl in the 1st week after surgery was highly predictive of remission (p=0.001).

Conclusion ETS allows for enhanced intrasellar identification of adenomatous tissue, providing remission rates that are comparable to traditional microsurgery for CD. The best predictor of remission remains induction of profound hypocortisolemia in the early postoperative period.

Management and outcomes of pituitary apoplexy

pituitary apoplexy

J Neurosurg 122:1450–1457, 2015

This study was undertaken to analyze the predisposing factors, clinical presentation, therapeutic management, and clinical recovery in patients with pituitary apoplexy, with an emphasis on the long-term visual, endocrine, and functional outcomes.

Methods The authors performed a retrospective analysis of consecutive cases involving patients treated at Mayo Clinic between 1992 and 2013. Patients were included in the study only if they had 1) abrupt onset of severe headache or visual disturbance in the presence of a pituitary adenoma and 2) radiological or surgical confirmation of a pituitary mass. The primary endpoints of analysis were the visual (ocular motility, visual fields, and visual acuity), endocrine, and functional outcomes (using the modified Rankin Scale).

Results Eighty-seven patients were identified (57 males and 30 females, mean age 50.9 years, range 15–91 years). Twenty-two patients (25.3%) had a known pituitary adenoma. Hypertension was the most common associated factor (39%). Headache was the most frequent presenting symptom (89.7%), followed by visual abnormalities (47.1%). Cranial nerve palsies were present in 39% and visual field defects in 34.1%. MRI detected hemorrhage in 89% patients, as compared with 42% detected by CT scan. Sixty-one patients (70.1%) underwent surgery during acute hospitalization (median time from apoplexy 5 days, IQR 3–10 days), 8 (9.2%) had delayed surgery, and 18 (20.7%) were treated conservatively. Histopathological examination revealed adenoma with pure necrosis in 18 (30%), pure hemorrhage in 4 (6.7%), and both in 6 (10%) patients. Four patients died during hospitalization. The average duration of follow-up was 44.2 ± 43.8 months. All survivors were independent and had complete resolution or substantial improvement in eye movements and visual fields at the last follow-up. Many patients needed long-term hormonal replacement with levothyroxine (62.7%) and cortisol (60%). Daily desmopressin was needed in 23% of all surgical patients at 3 months (versus none of the medically treated) and this requirement decreased slightly over time. Regrowth of pituitary adenoma was seen in 7 patients (8.6%). There were no statistically significant differences in any of the outcome measures across the treatment groups.

Conclusions The outcome of most patients with pituitary apoplexy is excellent. Selected patients can be managed conservatively, and patients with severe neuro-ophthalmological deficits treated with early surgery can achieve an excellent recovery.

Invasion of the cavernous sinus space in pituitary adenomas: endoscopic verification and its correlation with an MRI-based classification

Invasion of the cavernous sinus space in pituitary adenomas- endoscopic verification and its correlation with an MRI-based classification

J Neurosurg 122:803–811, 2015

An important prognostic factor for the surgical outcome and recurrence of a pituitary adenoma is its invasiveness into parasellar tissue, particularly into the space of the cavernous sinus (CS). The aims of this study were to reevaluate the existing parasellar classifications using an endoscopic technique and to evaluate the clinical and radiological outcomes associated with each grade.

Methods The authors investigated 137 pituitary macroadenomas classified radiologically at least on one side as Grade 1 or higher (parasellar extension) and correlated the surgical findings using an endoscopic technique, with special reference to the invasiveness of the tumor into the CS. In each case, postoperative MRI was performed to evaluate the gross-total resection (GTR) rate and the rate of endocrinological remission (ER) in functioning adenomas.

Results The authors found a 16% rate of CS invasion during surgery for these macroadenomas. Adenomas radiologically classified as Grade 1 were found to be invasive in 1.5%, and the GTR/ER rate was 83%/88%. For Grade 2 adenomas, the rate of invasion was 9.9%, and the GTR/ER rate was 71%/60%. For Grade 3 adenomas, the rate of invasion was 37.9%, and the GTR/ER rate was 75%/33%. When the superior compartment of the CS (Grade 3A) was involved, the authors found a rate of invasion that was lower (p < 0.001) than that when the inferior compartment was involved (Grade 3B). The rate of invasion in Grade 3A adenomas was 26.5% with a GTR/ER rate of 85%/67%, whereas for Grade 3B adenomas, the rate of surgically observed invasion was 70.6% with a GTR/ER rate of 64%/0%. All of the Grade 4 adenomas were invasive, and the GTR/ER rate was 0%. A comparison of microscopic and endoscopic techniques revealed no difference in adenomas with Grade 1 or 4 parasellar extension. In Grade 2 adenomas, however, the CS was found by the endoscopic technique to be invaded in 9.9% and by microscopic evaluation to be invaded in 88% (p < 0.001); in Grade 3 adenomas, the difference was 37.9% versus 86%, respectively (p = 0.002). Grade 4 adenomas had a statistically significant lower rate of GTR than those of all the other grades. In case of ER only, Grade 1 adenomas had a statistically significant higher rate of remission than did Grade 3B and Grade 4 adenomas.

Conclusions The proposed classification proved that with increasing grades, the likelihood of surgically observed invasion rises and the chance of GTR and ER decreases. The direct endoscopic view confirmed the low rate of invasion of Grade 1 adenomas but showed significantly lower rates of invasion in Grade 2 and 3 adenomas than those previously found using the microscopic technique. In cases in which the intracavernous internal carotid artery was encased (Grade 4), all the adenomas were invasive and the GTR/ER rate was 0%/0%. The authors suggest the addition of Grades 3A and 3B to distinguish the strikingly different outcomes of adenomas invading the superior CS compartments and those invading the inferior CS compartments.

Long-term Results of Endonasal Endoscopic Transsphenoidal Resection of Nonfunctioning Pituitary Macroadenomas

Results non-functioning macroadenomas

Neurosurgery 76:42–53, 2015

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.

OBJECTIVE: To discuss the long-term outcomes after endoscopic endonasal transsphenoidal surgery for nonfunctioning pituitary macroadenomas.

METHODS: This is a retrospective study. Patients were included only if they had at least 5 years of clinical and imaging follow-up after surgery.

RESULTS: 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 cm3 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.

CONCLUSION: 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.

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma

J Neurosurg 121:1166–1175, 2014

The loss of anatomical landmarks, frequently invasive tumor growth, and tissue changes make transsphenoidal reoperation of nonfunctioning pituitary adenomas (NFAs) challenging. The use of intraoperative MRI (iMRI) may lead to improved results. The goal of this retrospective study was to evaluate the impact of iMRI on transsphenoidal reoperations for NFA.

Methods. Between September 2002 and July 2012, 109 patients underwent reoperations in which 111 transsphenoidal procedures were performed and are represented in this study. A 1.5-T Magnetom Sonata Maestro Class scanner (Siemens) was used for iMRI. Follow-up iMRI scans were acquired if gross-total resection (GTR) was suspected or if no further removal seemed possible.

Results. Surgery was performed for tumor persistence and regrowth in 26 (23%) and 85 (77%) patients, respectively. On the initial iMRI scans, GTR was confirmed in 19 (17%) patients. Remnants were located as follows: 65 in the cavernous sinus (71%), 35 in the suprasellar space (38%), 9 in the retrosellar space (10%). Additional resection was possible in 62 (67%) patients, resulting in a significant volume reduction and increased GTR rate (49%). The GTR rates of invasive tumors on initial iMRI and postoperative MRI (poMRI) were 7% and 25%, respectively. Additional remnant resection was possible in 64% of the patients. Noninvasive tumors were shown to be totally resected on the initial iMRI in 31% of cases. After additional resection for 69% of the procedures, the GTR rate on poMRI was 75%. Transcranial surgery to resect tumor remnants was indicated in 5 (5%), and radiotherapy was performed in 29 (27%) patients. After GTR, no recurrence was detected during a mean follow-up of 2.2 ± 2.1 years.

Conclusions. The use of iMRI in transsphenoidal reoperations for NFA leads to significantly higher GTR rates. It thus prevents additional operations and reduces the number of tumor remnants. The complication rates do not exceed the incidences reported in the literature for primary transsphenoidal surgery. If complete tumor resection is not possible, iMRI guidance can facilitate tumor volume reduction.

MicroRNAs as Biomarkers in Pituitary Tumors

MicroRNAs_as_Biomarkers_in_Pituitary_Tumors

Neurosurgery 75:181–189, 2014

The use of extracellular microRNAs (miRNAs) as circulating biomarkers is currently leading to relevant advances in the diagnosis and assessment of prognosis of several diseases.

Specific miRNAs have also been shown to play a role in the pathophysiology of many neoplastic and non-neoplastic diseases. A number of studies have demonstrated that miRNAs show differential expression in various tumors, such as in the prostate, ovary, lung, breast, brain, and pituitary.

Recent findings have built connections between miRNAs that are deregulated within the tumor and their presence in peripheral blood. MiRNAs have been shown to be stable in the blood where they are present in either free and/or uncomplexed form, as well as packed in microvesicles, exosomes, and apoptotic bodies, or bound to different proteins.

Because the pituitary is a highly vascularized organ that releases hormones into the circulation, miRNAs would be useful biomarkers for the diagnosis of pituitary tumors, as well as for predicting or detecting recurrence after surgery.

Here we review the biological significance of miRNAs in pituitary tumors and the potential value of circulating miRNAs as biomarkers.

The chicken egg and skull model of endoscopic endonasal transsphenoidal surgery improves trainee drilling skills

Chicken egg and skull endoscopic models

Acta Neurochir (2014) 156:1403–1407

We verified the effectiveness of training in endoscopic endonasal transsphenoidal surgery (eETSS) techniques using chicken eggs and a skull model.

Methods We verified the area of eggshell removed by drilling when five residents and four experts used the chicken eggs and a skull model.

Results When residents performed drilling on 10 eggs, a mean (± standard deviation [SD]) area of 31.2 ± 17.5 mm2 was removed from the first egg, and 104.8 ± 3.3 mm2 from the tenth and final egg, representing an increase in area and a decrease in SD. The experts performed the same drilling operation on a single egg, and removed a mean area of 257± 31.7 mm2. These results demonstrated that skills improved as a result of this training, and suggested that this method was also capable of overcoming the initial individual differences in the amount of force applied and ability. An obvious difference between residents and experts was seen in the area removed (p = 0.00011); however, this was attributed to differences in endoscopic manipulation, rather than drilling skill.

Conclusion Our findings suggest that this training method could be adequate for acquiring eETSS techniques. Although experts showed superior endoscopic manipulation, residents may also be able to acquire adequate endoscopic skills through further training, and our training method appears to offer an effective means of improving eETSS techniques.

Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas

Endoscopic resection of giant pituitary adenomas

J Neurosurg 121:75–83, 2014

While the use of endoscopic approaches has become increasingly accepted in the resection of pituitary adenomas, limited evidence exists regarding the success of this technique for patients with large and giant pituitary adenomas. This study reviews the outcomes of a large cohort of patients with large and giant pituitary adenomas who underwent endoscopic endonasal transsphenoidal surgery at the authors’ institution and focuses on identifying factors that can predict extent of resection and hence aid in developing guidelines and indications for the use of endoscopic endonasal transsphenoidal surgery versus open craniotomy approaches to large and giant pituitary adenomas.

Methods. The authors reviewed 487 patients who underwent endoscopic endonasal transsphenoidal resection of sellar masses. From this group, 73 consecutive patients with large and giant pituitary adenomas (defined as maximum diameter ≥ 3 cm and tumor volume ≥ 10 cm3) who underwent endoscopic endonasal transsphenoidal surgery between January 1, 2006, and June 6, 2012, were included in the study. Clinical presentation, radiological studies, laboratory investigations, tumor pathology data, clinical outcomes, extent of resection measured by volumetric analysis, and complications were analyzed.

Results. The mean preoperative tumor diameter in this series was 4.1 cm and the volume was 18 cm3. The average resection rate was 82.9%, corresponding with a mean residual volume of 3 cm3. Gross-total resection was achieved in 16 patients (24%), near-total in 11 (17%), subtotal in 24 (36%), and partial in 15 (23%). Seventy-three percent of patients experienced improvement in visual acuity, while 24% were unchanged. Visual fields were improved in 61.8% and unchanged in 5.5%. Overall, 27 patients (37%) experienced a total of 32 complications. The most common complications were sinusitis (14%) and CSF leak (10%). Six patients underwent subsequent radiation therapy because of aggressive tumor histopathology. No deaths occurred in this cohort of patients. Statistically significant predictors of extent of resection included highest Knosp grade (p = 0.001), preoperative tumor volume (p = 0.025), preoperative maximum tumor diameter (p = 0.002), hemorrhagic component (p = 0.027), posterior extension (p = 0.001), and sphenoid sinus invasion (p = 0.005).

Conclusions. Endoscopic endonasal transsphenoidal surgery is an effective treatment method for patients with large and giant pituitary adenomas, which results in high (> 80%) rates of resection and improvement in visual function. It is not associated with high rates of major complications and is safe when performed by experienced surgeons. The preoperative Knosp grade, tumor volume, tumor diameter, hemorrhagic components on MRI, posterior extension, and sphenoid sinus invasion may allow a prediction of extent of resection and in these patients a staged operation may be required to maximize extent of resection.

Avoidance of postoperative epistaxis and anosmia in endonasal endoscopic skull base surgery

Avoid anosmia and epistaxis in EEA

Acta Neurochir (2014) 156:1393–1401

Most endoscopic transsphenoidal approaches jeopardize the sphenopalatine artery and septal olfactory strip (SOS), increasing the risk of postoperative anosmia and epistaxis while precluding the ability to raise pedicled nasoseptal flaps (NSF). We describe a bilateral “rescue flap” technique that preserves the mucosa containing the nasal-septal vascular pedicles and the SOS. This approach can reduce the risk of postoperative complications, including epistaxis and anosmia.

Methods A retrospective analysis was conducted of all patients who underwent endoscopic transsphenoidal surgery with preservation of both sphenopalatine vascular pedicles and SOS. In a recent subset of patients, olfactory assessment was performed.

Results Of 174 consecutive operations performed in 161 patients, bilateral preservation of the sphenopalatine vascular pedicle and SOS was achieved in 139 (80 %) operations, including 31 (22 %) with prior transsphenoidal surgery. Of the remaining 35 operations, 18 had a planned formal NSF and 17 had prior surgery or extensive lesions precluding use of this technique. Of pituitary adenomas, RCCs or sellar arachnoid cysts, 118 (94 %) underwent this approach, including 91% of patients who had prior surgery. Preoperative olfaction function was maintained in 97 % of patients that were tested. None of the patients had postoperative arterial epistaxis.

Conclusion Preservation of bilateral sphenopalatine vascular pedicles and the SOS is feasible in over 90 % of patients undergoing endonasal endoscopic surgery for pituitary adenomas and RCCs. This approach, while not hindering exposure or limiting instrument maneuverability, preserves the nasoseptal vasculature for future NSF use if needed and appears to minimize the risks of postoperative arterial epistaxis and anosmia.

Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older

Pituitary adenomas patients aged 80

Neurosurg Rev (2014) 37:269–277

To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated.

From1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima and Hiroshima University hospitals in Japan. Ten (1.1 %) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients.

The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2–3 on American Society of Anesthesiologists’ Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered.

Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients’ general condition is well preserved and pituitary hormonal deficiency is adequately replaced.

Transsphenoidal cyst cisternostomy with a keyhole dural opening for sellar arachnoid cysts

sellar cysts

Neurosurg Rev (2014) 37:261–267

A less invasive transsphenoidal approach with a keyhole dural opening for intrasellar arachnoid cysts is described. This approach was used to address seven sellar cystic lesions with suprasellar extension; they were six intrasellar arachnoid cysts (IACs) and one Rathke’s cleft cyst (RCC).

In all cases, preoperative MRI revealed cerebrospinal fluid (CSF) intensity on both T1- and T2-weighted images. On preoperative contrast-enhanced MRI, five of the six IACs manifested posterior displacement of the flattened pituitary gland toward the dorsum sellae; one of the six IACs and the RCC exhibited a flattened pituitary gland on the anterior surface of the cyst.

Wide cyst cisternostomy through a keyhole dural opening was carried out safely using a microscope with the support of a thin angled endoscope (30° and/or 70°, diameter 2.7 mm). As we aimed to avoid iatrogenic injury of the pituitary function, we found it difficult to obtain a sufficiently wide and precise opening of the cyst wall when the pituitary gland was located on the anterior surface of the cyst wall.

Our approach facilitates safe cyst cisternostomy as wide as that obtainable by transcranial manipulation. In addition, CSF leakage is prevented by dural plasty using the fascia lata and stitching with 6-0 monofilament sutures. This technique can be adapted to address various sellar cystic lesions. However, as the posterior or anterior displacement of the normal pituitary gland in the presence of IACs or RCCs, respectively, affects the width of the cyst opening, our technique is more suitable for IACs than RCCs.

Surgical complications after transsphenoidal microscopic and endoscopic surgery for pituitary adenoma: a consecutive series of 506 procedures

Treatment of acromegaly by endoscopic transsphenoidal surgery

Acta Neurochir (2014) 156:441–449

This single-institution, consecutive series of transsphenoidal procedures included all patients in a defined population of 2.6 million inhabitants who underwent surgery during a specific time period.

Objective We sought to determine the surgical complication rate and overall survival rate after transsphenoidal surgery for pituitary adenoma.

Methods All transsphenoidal procedures for histologically verified pituitary adenomas performed between September 2002 and February 2011 at our institution were included in this study. The data were obtained from a prospectively collected database and from reviewing medical records. No patients were lost to follow-up, and the median follow-up time was 28 months.

Results A total of 506 transsphenoidal procedures were performed on 446 patients. There were 268 microscopic and 238 endoscopic procedures involving 352 non-functioning and 154 hormone-secreting adenomas. A total of 73 % of the procedures were primary surgeries, and 27 % were repeat surgeries for tumor recurrence. The overall complication rate was 9.1 %. The three most frequent complications were cerebrospinal fluid (CSF) leakage (4.7 %), meningitis (2 %), and visual deterioration (2 %). Multivariate analyses showed that the overall risk for complications increased with older age, surgery for recurrent tumors, and surgery performed by a low-volume surgeon. There was no significant difference in the overall complication rate between the microsurgical and endoscopic techniques. The rate of surgical mortality was 0.6 %, and the overall survival rates at 1 and 5 years were 95 % and 90 %, respectively. The only negative predictor of survival was older age.

Conclusions Transsphenoidal surgery for pituitary adenomas has a low complication rate and a low rate of mortality. We did not find a significant difference in the complication rate between endoscopic and microscopic techniques.

Identification of the internal carotid artery at the superior part of the cavernous sinus during endoscopic endonasal cavernous sinus tumor surgery

Identification of the internal carotid artery in cavernous sinus during endoscopic endonasal cavernous sinus tumor surgery

Acta Neurochir (2014) 156:475–479

Identification of the internal carotid artery (ICA) is essential for successful endoscopic endonasal cavernous sinus tumor surgery. This study aimed to develop a method for identifying the ICA in cavernous sinus tumors at the superior part of the cavernous sinus.

Methods Ten fresh cadavers were studied with a 4-mm 0° and 30° endoscope to identify surgical landmarks of the ICA in the cavernous sinus. Clinical cases of cavernous sinus tumors were surgically treated using an endoscopic transpterygoid approach.

Results Anatomical study indicated the ICA at the superior part of the cavernous sinus can be identified using three steps: 1) exposure of the optic nerve sheath by drilling the optic canal; 2) identification of the proximal orifice of the optic nerve sheath at the transition of the optic nerve sheath and dura mater of the tuberculum sellae; and 3) identification of the clinoid segment of the ICA at the distal dural ring just below the proximal orifice of the optic nerve sheath. Although the ICA was encased and transposed by tumors in preliminary surgical cases, the clinoid segment of the ICA was safely exposed at the superior part of the cavernous sinus using this method.

Conclusions Dural structures around the cavernous sinus are key to identifying the ICA at the superior part of the cavernous sinus. This method is expected to reduce the risk of ICA injury during endoscopic endonasal surgery for cavernous sinus tumors.

Intraoperative MRI for transsphenoidal pituitary surgery

Intraoperative MRI for transsphenoidal pituitary surgery

J Neurosurg 120:346–356, 2014

Intraoperative MRI (iMRI) provides updated information for neuronavigational purposes and assessments on the status of resection during transsphenoidal surgery (TSS). The high-field technique additionally provides information about vascular structures at risk and precise information about extrasellar residual tumor, making it readily available during the procedure. The imaging, however, extends the duration of surgery. To evaluate the benefit of this technique, the authors conducted a retrospective study to compare postoperative outcome and residual tumor in patients who underwent conventional microsurgical TSS with and without iMRI.

Methods. A total of 143 patients were assessed. A cohort of 67 patients who had undergone surgery before introduction of iMRI was compared with 76 patients who had undergone surgery since iMRI became routine in TSS at the authors’ institution. Residual tumor, complications, hormone dependency, biochemical remission rates, and improvement of vision were assessed at 6-month follow-up. A volumetric evaluation of residual tumor was performed in cases of parasellar tumor extension.

Results. The majority of patients in both groups suffered from nonfunctioning pituitary adenomas. At the 6-month follow-up assessment, vision improved in 31% of patients who underwent iMRI-assisted surgery versus 23% in the conventional group. One instance of postoperative intrasellar bleeding was found in the conventional group. No major complications were found in the iMRI group. Minor complications were seen in 9% of patients in the iMRI group and in 5% of those in the conventional group. No differences between groups were found for hormone dependency and biochemical remission rates. Time of surgery was significantly lower in the conventional treatment group. Overall a residual tumor was found after surgery in 35% of the iMRI group, and 41% of the conventional surgery group harbored a residual tumor. Total resection was achieved as intended significantly more often in the iMRI group (91%) than in the conventional group (73%) (p < 0.034). Patients with a planned subtotal resection showed higher mean volumes of residual tumor in the conventional group. There was a significantly lower incidence of intrasellar tumor remnants in the iMRI group than in the conventional group. Progression-free survival after 30 months was higher according to Kaplan-Meier analysis with the use of iMRI, but a statistically significant difference could not be shown.

Conclusions. The use of high-field iMRI leads to a significantly higher rate of complete resection. In parasellar tumors a lower residual volume and a significantly lower rate of intrasellar tumor remnants were shown with the technique. So far, long-term follow-up is limited for iMRI. However, after 2 years Kaplan-Meier analyses show a distinctly higher progression-free survival in the iMRI group. No significant benefit of iMRI was found for biochemical remission rates and improvement of vision. Even though the surgical time was longer with the adjunct use of iMRI, it did not increase the complication rate significantly. The authors therefore recommend routine use of high-field iMRI for pituitary surgery, if this technique is available at the particular center.

Transpetrosal approach for challenging craniopharyngiomas

Transpetrosal approach for challenging craniopharyngiomas

J Neurosurg 120:1–11, 2014

Retrochiasmatic craniopharyngiomas are surgically challenging tumors. Retrochiasmatic craniopharyngiomas with complicated conditions such as large diameter, major calcification, or significant extension to the third ventricle or posterior fossa present surgical challenges; moreover, recurrent retrochiasmatic craniopharyngiomas are particularly formidable challenges. Although the transpetrosal approach to retrochiasmatic craniopharyngiomas published by Hakuba in 1985 can provide unique advantageous exposure of the retrochiasmatic area to allow safe neurovascular dissection and facilitate radical tumor removal, the procedure is viewed as complicated and time consuming and has a high risk of damaging hearing functions. The authors have modified Hakuba’s technique to minimize petrosectomy and reduce surgical complications and have applied this modified approach to retrochiasmatic craniopharyngiomas with complicated conditions. In this study, the authors describe their technique and surgical outcomes to elucidate the role of this modified transpetrosal approach for retrochiasmatic craniopharyngiomas with complicated conditions. This is the first study to report surgical outcomes of the transpetrosal approach for retrochiasmatic craniopharyngiomas.

Methods. Between 1999 and 2011, the minimum anterior and posterior combined (MAPC) transpetrosal approach, which is a modification of Hakuba’s transpetrosal approach, was applied in 16 cases of retrochiasmatic craniopharyngiomas with complicated conditions. Eight cases were recurrent tumors, 4 had previously received radiotherapy, 11 had a large diameter, 10 had large calcification, 15 had superior extension of the tumor into the third ventricle, and 10 had a posterior extension of the tumor that compressed the midbrain and pons. In all 16 patients, more than 2 of these complicated conditions were present. The follow-up duration ranged from 0.8 to 12.5 years (mean 5.3 years). Surgical outcomes assessed were the extent of resection, surgical complications, visual function, endocrinological status, and neuropsychological function. Five-year and 10-year recurrence-free survival rates were also calculated.

Results. Gross-total or near-total resection was achieved in 15 cases (93.8%). Facial nerve function was completely maintained in all 16 patients. Serviceable hearing was preserved in 15 cases (93.8%). Visual function improved in 13 out of 14 cases (92.9%) that had visual disturbance before surgery. None of the patients experienced deterioration of their visual function. Twelve cases had endocrinological deficit and received hormonal replacement before surgery. New endocrinological deficit occurred in 2 cases (12.5%). Neuropsychological function was maintained in 14 cases (87.5%) and improved in 1 case (6.3%). One case that had received previous conventional radiotherapy treatment showed a gradual decline in neuropsychological function. The 5-year and 10-year recurrence-free survival rates were both 86.5%.

Conclusions. The authors obtained good results by using the MAPC transpetrosal approach for the removal of retrochiasmatic craniopharyngiomas with complicated conditions. The MAPC transpetrosal approach should be considered as a therapeutic option for selected cases of retrochiasmatic craniopharyngiomas with complicated conditions.

Treatment of acromegaly by endoscopic transsphenoidal surgery

Treatment of acromegaly by endoscopic transsphenoidal surgery

J Neurosurg 119:1467–1477, 2013

Acromegaly is a disease that has significant morbidity and mortality related to high levels of growth hormone (GH) and insulin-like growth factor–I (IGF-I), and is usually caused by pituitary adenomas. The goal in this study was to investigate the role of endoscopic transsphenoidal surgery and surgical experience in the treatment of GH adenoma cases in relation to surgical results and hormonal cure rates, and to perform a review of the literature.

Methods. The authors present a retrospective analysis of 214 GH adenoma cases. Restoration of IGF-I levels to normal for age and sex, suppression of GH levels below 0.4 μg/L on the oral glucose tolerance test, and demonstration of the total removal of the tumor on MRI studies obtained after administration of contrast material at the 3-month postoperative follow-up visit were the criteria for cure.

Results. In total 214 patients with a mean age of 41.9 ± 12 years (range 17–75 years) and a male/female ratio of 106/108 were enrolled in the study. Cure was achieved in 134 (62.6%) of 214 patients. One hundred sixty-nine patients were primary cases, and of these 109 (64.5%) were cured, whereas 61 patients were previously operated cases and of these 25 (41%) were cured. With a 51.1% decrease in the 1st month postoperatively, IGF-I levels were found to be predictive of cure (74.4% sensitivity and 73.7% specificity). Cut-off values for GH levels in predicting cure for the 1st day, 1st week, and 1st month postoperatively were 2.33, 2.05, and 2.25 μg/L, respectively. The cut-off value for surgical experience was 57 for primary surgeries (58.5% cure rate before this cut-off value compared with 72.6% after it; p = 0.025) and 108 for all operations (45.8% vs 79.4%, p = 0.037). Although 28 patients were found to be in remission according to the criteria in 2000, they were not in remission according to the new consensus criteria. Nine of these cases (32.1%) had random GH levels < 1 μg/L at the 1-year follow-up. The 1-year IGF-I and GH levels in these 28 patients showed no significant difference when compared with the cases defined as cured according to the current criteria.

Conclusions. In acromegaly treatment, transsphenoidal endoscopic surgery performed by an expert senior surgeon and increased surgical experience are important for higher cure rates. Random GH levels < 2.33 μg/L after the 1st day postoperatively and a > 50% decrease in IGF-I levels after the 1st month postoperatively are predictive of cure. Moreover, there is no urgency for additional therapy in patients with GH levels of 0.4–1 μg/L and MRI sequences showing no tumor at the 3-month follow-up, because for these cases remission can be achieved at the 1-year follow-up.

Sphenoid sinus anatomy and suprasellar extension of pituitary tumors

Sphenoid sinus anatomy

J Neurosurg 119:669–674, 2013

As tumors enlarge, they generally grow along paths of least resistance. For pituitary macroadenomas, extrasellar extension into the suprasellar region, cavernous sinus, or sphenoid sinus may occur. The sphenoid sinus is known to have a variable anatomical configuration, and the authors hypothesize that certain anatomical factors may resist tumor expansion into the sphenoid sinus, thereby directing tumor growth into the suprasellar space. In this paper the authors’ goal was to determine if sphenoid anatomy influences pituitary tumor growth.

Methods. The authors conducted a retrospective analysis of 106 consecutive surgical cases of pituitary macroadenoma. Patient demographics, suprasellar extension, sellar width, and features of the sphenoid intersinus septum were recorded on radiographic review. The chi-square test, t-test, logistic regression, and classification and regression tree analysis were used for statistical analysis.

Results. Of the 106 patients included in the study, 71 (67%) demonstrated suprasellar extension of their tumor. Patients with suprasellar tumor extension had significantly greater intersinus septum width (width > 1.27 mm: OR = 14.32; p = 0.0012) and were significantly older (age > 54 yrs: OR = 3.33; p = 0.0176). They also tended to be male and to have two or more sphenoid partitions (OR = 6.58; p = 0.0306). While patients with suprasellar extension tended to be more likely to have a midline partition and a larger sellar width than their counterparts, these differences did not reach statistical significance.

Conclusions. Certain aspects of the sphenoid sinus anatomy may function to resist pituitary tumor growth into the sphenoid sinus. Progressive enlargement of pituitary macroadenomas may extend in a suprasellar direction, in part, as a consequence of the sphenoid sinus anatomy.

Endoscopic Transsphenoidal Surgery for Cushing Disease

Endoscopic for Cushing Disease

Neurosurgery 72:240–247, 2013

The efficacy of endoscopic transsphenoidal surgery (ETS) for Cushing disease has not been clearly established.

OBJECTIVE: To assess efficacy of a pure endoscopic approach for treatment of Cushing disease and determine predictors of remission.

METHODS: A prospectively acquired database of 61 patients undergoing ETS was reviewed. Remission was defined as postoperative morning serum cortisol of ,5 mg/dL or normal or decreased 24-hour urine-free cortisol level in follow-up.

RESULTS: Overall, hypercortisolemia resolved in 58 of 61 patients (95%) by discharge. Tumor size did not predict resolution of hypercortisolemia at discharge (microadenomas [97%], magnetic resonance imaging-negative Cushing [100%], macroadenomas [87%]). At 2- to 3-month evaluations, 45 of 49 patients (91.8%) were in remission. Fifty patients were followed for at least 12 months (mean, 28 months; range, 12-72). Forty-two (84%) achieved remission from a single ETS. In these patients, there was no significant difference in remission rates between microadenomas (93%), magnetic resonance imaging-negative (70%), and macroadenomas (77%). Patients with history of previous surgery (n = 14, 23%) were 9 times less likely to achieve follow-up remission (P = .021). In-house cortisol level of ,5.7 mg/dL provided the best prediction of follow-up remission (sensitivity 88.6%, specificity 83.3%). Postoperative diabetes insipidus occurred transiently in 7 patients (9%) and permanently in 3 (5%). One patient experienced postoperative cerebrospinal fluid leak that resolved with further surgery.

CONCLUSION: ETS for Cushing disease provides high rates of remission with low rates of complications regardless of size. Although patients with a history of previous surgery are less likely to achieve remission, the majority can still achieve remission following treatment.

KEYWORDS:

Transphenoidal surgery in acromegalic patients: anatomical considerations and potential pitfalls

Transphenoidal surgery in acromegalic patients- anatomical considerations and potential pitfalls.1 Transphenoidal surgery in acromegalic patients- anatomical considerations and potential pitfalls

Acta Neurochir (2013) 155:125–130

Transphenoidal surgery is an effective treatment for acromegalic patients with growth hormone (GH) producing pituitary adenomas. Since acromegaly is a systemic disease which causes multiple bony alterations, we hypothesized that it could affect the sphenoid sinus anatomy. The aim of the study was to determine whether acromegalic patients have sphenoid sinus alterations with potential surgical impact.

Methods Fourty-six consecutive patients (23 acromegalics- GH group, 23 non-acromegalics-nGH group) undergoing transphenoidal surgery were included in this study. Preoperative volumetric CT scan of the head was used to assess the following anatomic characteristics: type of sphenoid sinus (sellar, pre-sellar, conchal); number of intrasphenoid septa; number of carotid-directed septa; intercarotid distance; depth of the sphenoid sinus; depth and size of the sella.

Results The sphenoid sinus was of the pre-sellar/conchal type in 26 % of the patients with acromegaly (n023) versus 9 % of the patients of the nGH group (n023). The number of intrasphenoid septations was significantly higher in the GH group than in the nGH group (P=.03). Interestingly, the intercarotid distance was smaller in GH patients than in nGH displaying a trend toward significance (P=.05). The sphenoid bone was deeper in the GH group as compared to the nGH group (P=.01) but the distance sphenoid sinus-sella was reduced (P<.01). Finally, the sella was not deeper, nor larger in acromegalic patients.

Conclusions The sphenoid sinus of acromegalic patients resulted in being deeper, characterized by more septa and by a reduced intercarotid distance. These alterations deserve special pre- and intraoperative care, being potentially responsible for surgical difficulties.