Transsphenoidal Extent of Resection Study

Study Overview
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Brief Summary
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The purpose of this research study is to compare the extent of resection (EOR) in patients with nonfunctioning pituitary adenomas undergoing transsphenoidal surgery using a microsurgical technique to those patients who have undergone surgery with a fully endoscopic technique. Another goal is to compare surgical complications, endocrine outcomes, visual outcomes, length of surgery, length of hospital stay, and readmission rates between the two transsphenoidal surgery techniques. This is an observational data collection study with no experimental procedures or experimental medicines. Endonasal transsphenoidal removal of a pituitary tumor is a unique procedure and there is little information comparing the two surgical techniques.

Detailed Description
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The treatment of choice for most patients with symptomatic nonfunctioning pituitary adenomas is transsphenoidal surgery to improve vision by decompression of the optic chiasm, to prevent the development of endocrine dysfunction, and to treat neurological symptoms such as headache or cranial neuropathies caused by the tumor. The most widely accepted surgical technique is microscopic transsphenoidal surgery, in which an operating microscope is used by the surgeon to provide surgical visualization and a nasal speculum is used to maintain the operative corridor. [1-4] Recently, fully endoscopic transsphenoidal surgery, in which surgical visualization is achieved using an endoscope, has been adopted by many pituitary surgeons because the technique offers superior panoramic and angled visualization of the surgical target and may permit greater tumor resection. [5-10] There is a vigorous debate in the neurosurgical community about the relative merits of the microscopic and endoscopic techniques. Proponents of the endoscopic technique argue that the superior visualization permits more aggressive tumor resection and better preservation of the normal pituitary gland. Proponents of the microscopic technique argue that it permits shorter operative times, results in similar surgical outcomes, and has a lower complication rate. Despite the adoption of fully endoscopic surgery by many surgeons, no prospective studies have compared the extent of tumor resection (EOR) between microscopic and endoscopic approaches. Numerous retrospective studies have established the efficacy of each approach, but only a few studies present comparative data.[11-13] Recently, McLaughlin et al. noted that the addition of endoscopy to microscopic pituitary surgery enhances tumor removal, particularly in patients with tumors greater than 20 mm in diameter. [14] This study raises the intriguing possibility that certain subgroups of patients (e.g. patients with larger tumors) may benefit from endoscopic surgery. In patients with smaller tumors with no cavernous sinus invasion, others have shown that the techniques achieve similar EOR. [15] That endoscopy may permit more complete tumor resections is a testable hypothesis.

Official Title
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Prospective Multicenter Cohort Study Comparing Extent of Tumor Resection Between Microscopic Transsphenoidal Surgery and Fully Endoscopic Transsphenoidal Surgery for Nonfunctioning Pituitary Adenomas

Conditions
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Pituitary Adenoma

Intervention / Treatment
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* Procedure: transsphenoidal surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with suspected nonfunctioning pituitary macroadenomas (≥ 1 cm) with planned transsphenoidal surgery Adults (age 18-80 years) Medically stable for surgery Reasonable expectation that patient will complete study and be available for follow-up assessments Exclusion Criteria: Prisoners Pregnant women Patients with suspected functioning pituitary adenoma Unable to obtain MRI of the pituitary (e.g., pacemaker, anaphylaxis to gadolinium, low GFR) Pituitary apoplexy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: microscopic<br>Microscopic transsphenoidal surgery, including endoscopic-assisted approach (350 subjects) | Procedure: transsphenoidal surgery<br> <br> |
| Active Comparator: endoscopic<br>Fully endoscopic transsphenoidal surgery (350 subjects) | Procedure: transsphenoidal surgery<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients who have complete tumor removal (gross total resection) based on MRI . | Postop MRI read by neuroradiologist | 3 months post surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| volume of residual tumor | volume, analyzed as a continuous variable; will be determined by manual segmentation using Dominator (www.dominator.com) software under the supervision of a board-certified neuroradiologist | 3 months after date of surgery | 
| percentage of tumor removed | Postop MRI tumor bed read by neuroradilogisy | 3 months post surgery | 
| postoperative cerebral-spinal fluid (CSF) leak | leakage from nose is a known complication, however, patients who have undergone a second surgery or had a lumbar drain placed to repair the problem will be documented | 6 months (continuous) from surgery | 
| postoperative meningitis | Determined by symptoms of headache, fever, neck stiffness, nausea and vomiting, and occasionally an altered level of consciousness. CSF culture may be positive for infection and may show elevated glucose and/or protein. CSF may be negative in aseptic meningitis. | 6 months (continuous) from surgery | 
| hypopituitarism | (morning cortisol <4.0ug/dL)(adrenocorticotropic hormone ACTH <6.0pg/mL)(follicular stimulating hormone FSH - mIU/mL. Female: follicular: <3.5; midcycle <4.7; luteal <1.7; postmenopausal <25.8. male <1.7)(luteinizing hormone LH - mIU/mL. Female: follicular <2.4; midcycle <14.0; luteal <1.0; postmenopausal <7.7)(estradiol - pg/mL. female: follicular <13; ovulation <86; luteal <44; postmenopausal <56)(insulin-like growth factor 1 IGF1: 101ng/mL)(testosterone total - ng/dL. Female <6.0; male <270.0)(prolactin ,3.3ng/mL)(thyroid stimulating hormone TSH <.45mU/L)(Thyroxine T4 Free <0.8ng/dL | 6 months post surgery | 
| diabetes insipidus (DI) | to be evaluated by pituitary endocrinologist; serum sodium value is > or equal to 147meq/dl OR if the patient received treatment for DI | 6 months post surgery | 
| visual outcomes | visual field deficits in this exam will be compared to pre-operative results. Confrontation visual field exam (Donder's test): The examiner will ask the patient to cover one eye and stare at the examiner. The examiner will then move his hand out of the patient's visual field and bring it back in. The examiner will use a slowly wagging finger or a hat pin for this. The patient signals the examiner when his hand comes back into view. Second option is a formal visual field exam (perimetry) performed by a neuro-ophthalmologist. | 3 months post surgery | 
| hypothyroidism | (thyroid stimulating hormone TSH <.45mU/L)(thyroxine T4Free <0.8ng/dL) | 6 months post surgery | 
| hypogonadism | (Testosterone (Total) - ng/dL. Female: < 6.0; Male: < 270.0) (Follicular Stimulating Hormone (FSH) - mIU/mL. Female - Follicular: < 3.5; Midcycle: <4.7; Luteal: < 1.7; Postmenopausal: < 25.8. Male - < 1.5)(Luteinizing Hormone LH - mIU/mL. Female: Follicular: < 2.4; Midcycle: <14.0; Luteal: < 1.0; Postmenopausal: < 7.7. Male: < 1.7)(Estradiol - pg/mL. Female: Follicular: < 13; Ovulation: < 86; Luteal: < 44; Postmenopausal: < 56. Male: < 15) | 6 months post surgery | 
| growth hormone deficiency | (insulin tolerance test: growth hormone <3μg/l)(IGF1 <77)(symptoms may include thin and dry skin, low energy, decreased strength and exercise tolerance, decreased muscle mass, weight gain especially around the waist, feelings of anxiety, depression, or sadness causing a change in social behavior | 6 months post surgery | 
| adrenal insufficiency | (morning serum cortisol <4.0ug/dL)(ACTH <6.0pg/mL)(sodium <135mEq/L)(abnormal ACTH [cosyntropin] stimulation test) | 6 months post surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pituitary, adenoma, transsphenoidal surgery