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Endocrine Gland Neoplasms

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

USE OF ENDOSPHENOIDAL COIL (ESC) TO OBTAIN MRI IMAGING OF THE PITUITARY GLAND

Michaela X Cortes

Prashant Chittiboina, M.D.

For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)

Background:

Pituitary tumors can cause problems by secreting hormones in the body. They can also problems by growing large and pushing on organs near the pituitary gland. The best treatment for such tumors is to remove them by surgery. But that may be sometimes difficult. Some tumors maybe too small to see. Some other tumors maybe so large that portions maybe left behind during surgery. The endosphenoidal coil (ESC) is a new magnetic resonance imaging (MRI) device. It fits in a small space made during surgery near the pituitary. Researchers want to see if it helps transmit MRI signals during surgery to make better images of the pituitary gland and tumors.

Objective:

To test the safety of using a new coil device to improve MRI imaging of pituitary tumors during surgery.

Eligibility:

Adults 18-85 years old who are having pituitary tumor surgery at NIH

Design:

Participants will be screened with:

* Medical history
* Physical exam
* Review of prior brain scans
* Blood and pregnancy tests

All participants will have MRI of pituitary gland. They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will lie still and get earplugs for loud sounds. A dye will be inserted into an arm vein by needle.

Participants will stay in the hospital for about 1 week. They will repeat screening tests.

Participants will have standard pituitary surgery. They will get medicine to go to sleep. The surgeon will create a path to the pituitary gland from under the lip.

During surgery, the ESC will be placed through the path to near the pituitary. Then an MRI will be done during surgery.

Then the ESC will be removed and standard surgery will continue.

Participants will get standard post-operative care under another protocol.

Tumors of the pituitary gland comprise up to 20% of all brain tumors. The central location and the small size of the pituitary gland make the management of tumors particularly challenging. Transsphenoidal surgery (TSS) to resect pituitary tumors is highly successful at achieving complete cure for functional pituitary adenomas. It is most successful when such adenomas can be localized by preoperative MRI of the pituitary. However, in some instances, small functional tumors cannot be visualized. In the case of Cushing s disease (CD), such non-visualization may be as high as 50%. The success of transsphenoidal surgery is substantially reduced in patients with negative MRI, as some of the adenomas that cause CD are so small that they are difficult to find during surgical exploration of the pituitary. Surgical success is also diminished when tumors invade the walls of the cavernous sinus. MRI of the pituitary lacks imaging resolution to detect such invasion and so the surgeon cannot perform a complete resection with surgery based on the preoperative MRI.

Signal to noise ratio (SNR) is the primary constraint on achieving high quality high resolution MRI images. SNR can be improved by longer scan times or by increasing the field strength of the MRI magnet. SNR is proportional to the square of imaging time, however, long imaging times are not clinically feasible. SNR is linearly proportional to field strength, however, replacing MRI magnets is cost prohibitive.

Another strong determinant of SNR is the proximity of the MRI receiver coil to the tissue being imaged. Placement of a coil in close proximity to the structure of interest dramatically increases SNR, often as much as 10-fold. Clinically this is routinely put into practice for superficial body parts, such as the temporomandibular joints, in which small coils are placed directly over the joints to achieve rapid high-resolution imaging. For deep structures, the use of superficial coils is of no benefit. This has led to the development of endocavitary coils, such as the endorectal coil used to image the prostate gland. Such coils are now in routine clinical use here at the NIH and elsewhere.

During routine TSS, the surgical approach to the pituitary provides a route for placement of imaging tools, such as handheld ultrasound and Doppler probes in close proximity to the gland. Extending this model to MRI imaging, we realized that an endocavitary surface coil within the sphenoid sinus will allow for a marked improvement in SNR for imaging the sella. To this end, we have developed an endosphenoidal coil (ESC), demonstrated its MRI safety, and performed preliminary studies in cadaver heads to determine that the ESC can be placed through the transsphenoidal approach. Placement of ESC needs no modification in the surgical TSS approach to the pituitary gland. The goal of this protocol is to examine the safety and feasibility of ESC placement and imaging during TSS.

Objective

To evaluate the feasibility and safety of using ESC during TSS.

Study Population

The study population will be up to 70 adult subjects with pituitary tumors that require TSS. Enrollment will be completed once 50 subjects have received the study procedure. The requested accrual ceiling of 70 subjects accounts for screening failures and drop-outs who do not receive the study procedure.

Design

This is a pilot study of 50 subjects requiring TSS for pituitary lesions. The subjects will undergo standard TSS resection of a pituitary adenoma in the intra-operative MR suite. Following standard surgical approach, the ESC will be placed into the sphenoid sinus, while the bone of the sellar floor is still intact. Routine clinical pituitary imaging with and without intravenous contrast will be performed for comparison with standard pituitary imaging. Additional higher resolution sequences will be performed as time allows. Following imaging, standard surgical resection will be performed. Surgeon will not view scans arising from the research procedure and therefore intraoperative clinical decisions making will not be influenced by the results of the research imaging.

Outcome Measures:

Primary Outcome Measure

Preliminary analysis of the data generated so far revealed that the ESC is well-designed to fit within the surgical workflow. However, the utility of ESC imaging was limited within the parameters of the standard sequences. Depending on the specific clinical indication for TSS, we found that the ESC could have differing roles as a surgical adjunct. For the current amended trial, feasibility of ESC will be evaluated as follows:

1. For microadenomas (pituitary adenomas smaller than 10 mm in diameter), the ability of ESC to confirm the location and size of adenomas.
2. For macroadenomas (pituitary adenomas larger than 10 mm in diameter), the ability of ESC to detect invasion of the cavernous sinus and/or parasellar structures (structures surrounding the pituitary gland).
3. For MRI negative cases, the ability to detect adenomas.

Safety Outcome Measure

We will evaluate the safety of the ESC as a surgical adjunct tool. We will evaluate whether the use of ESC causes local trauma, bleeding, burns or other unanticipated safety issues during TSS.

Exploratory Outcome Measures

Clinical utility of these images will be evaluated by comparing SNR and contrast to noise ratio (CNR) measurements obtained with the ESC to preoperative standard of care images.

1. Pituitary SNR with ESC MRI versus pre-operative standard of care images.
2. Pituitary to tumor Contrast to Noise Ratio (CNR) with ESC MRI versus pre-operative standard of care images.

Feasibility of Endosphenoidal Coil Placement for Imaging of the Sella During Transsphenoidal Surgery

.We do plan to share IPD. We will share all IPD that results in a publication on a public repository, as required by most journals. The data will be de-identified and anonymized.

The primary outcome of this study is the feasibility of using ESC as a clinical tool during transsphenoidal surgery. Feasibility will be assessed by the time added to a standard TSS procedure (measured from the time the TSS exposure is completed to the time to return to the operating position for completion of surgery).

National Institute of Neurological Disorders and Stroke (NINDS)

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Microscopic transsphenoidal surgery, including endoscopic-assisted approach (350 subjects)

Fully endoscopic transsphenoidal surgery (350 subjects)

transsphenoidal surgery

Andrew Little, MD

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.

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.

Transsphenoidal Extent of Resection Study

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

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

Postop MRI tumor bed read by neuroradilogisy

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

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.

(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

to be evaluated by pituitary endocrinologist; serum sodium value is \> or equal to 147meq/dl OR if the patient received treatment for DI

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.

(thyroid stimulating hormone TSH \<.45mU/L)(thyroxine T4Free \<0.8ng/dL)

(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)

(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

(morning serum cortisol \<4.0ug/dL)(ACTH \<6.0pg/mL)(sodium \<135mEq/L)(abnormal ACTH \[cosyntropin\] stimulation test)

Saint John's Cancer Institute

Swedish Medical Center

Northwestern University

Ohio State University

Washington University School of Medicine

University of Pittsburgh Medical Center

St. Joseph's Hospital and Medical Center, Phoenix

Clinical Research Operations Manager

Musculoskeletal Diseases

Rare Diseases

Acromegaly

Antineoplastic Agents

Gastrointestinal Agents

All Drugs and Chemicals

Octreotide

Antineoplastic Agents, Hormonal

Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery

Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured

Octreotide LAR

David M Kleinberg, MD

This is a randomized, multicenter trial with stratification done by a single radiologist at the coordinating center (NYU), and patients with comparable disease will be randomized to Sandostatin LAR treatment administered 1 time per month by IM injection for 3 months before (Arm A) or, for non-cured patients, after (Arm B) surgery. All patients will undergo transsphenoidal hypophysectomy. The impact of surgical debulking on responsiveness to Sandostatin LAR will be evaluated.The primary objective of this trial will be to determine whether surgery (debulking of pituitary adenomas) improves the response of patients with acromegaly to treatment with Octreotide LAR, when compared to Octreotide LAR therapy alone.

The current goal of treatment for people with acromegaly is normalization of both growth hormone (GH) and insulin-like-growth-factor-1 (IGF-1) levels. Normalization of GH and IGF-1 levels attenuates the morbidity (hypertension, cardiovascular disease, sleep apnea, increased cancer risk, arthritis) and increased mortality associated with persistent GH and IGF-1 elevation. The optimal approach to achieving these goals in patients with pituitary macroadenomas remains controversial. Available treatment modalities include transsphenoidal hypophysectomy, medical therapy (somatostatin analogues and/or dopaminergic agonists), radiotherapy, or a combination or these interventions. No randomized trials have been conducted to investigate whether surgical debulking of pituitary macroadenomas enhances the efficacy of medical therapy. This study is designed to rigorously investigate whether surgical debulking increases the efficacy of a long-acting depot somatostatin preparation, Sandostatin LAR, so that evidence-based optimal care may be offered to patients with acromegaly.

Surgical Debulking of Pituitary Adenomas

Does Surgical Debulking Of Pituitary Adenomas Improve Responsiveness To Octreotide LAR In The Treatment Of Acromegaly: An Investigator-Initiated Study

Nadir growth hormone \<1 ng/mL during a standard 2 hour oral glucose tolerance test using 75 g glucose and normal IGF-I according to age and gender-matched standards.

NYU Langone Health

Medical therapy with Octreotide LAR 30 mg/month for 3 months preceding surgery

Octreotide LAR

Medical Treatment by Octreotide LAR

Surgical debulking of pituitary tumor followed by Octreotide LAR if not surgically cured

Octreotide LAR

transsphenoidal surgery

Surgical Debulking Followed by Octreotide LAR

Total

Age, Categorical

Sex: Female, Male

American Indian or Alaskan

Asian or Pacific Islander

Black, Not of Hispanic-American Origin

Hispanic-American

White, not of Hispanic-American Origin

Other or Unknown

Race/Ethnicity, Customized

United States

Germany

Italy

Region of Enrollment

David Kleinberg

Percentage of Responders (Primary Medical Treatment in Arm 1, Primary Surgical Treatment in Arm 2)

Percentage of Responders (All Treatments)

Percentage of Responders (Only Including Surgical Failures in Arm 2)

Overall Study

Symptoms and General Pathology

Postoperative Complications

The 'HYP'OP' cohort comprises patients who underwent endoscopic endonasal surgery (EES) for pituitary adenoma during a 10-year period spanning from January 2012 to June 2022 at the Nancy University Hospital. Post-operative hospitalization in our endocrinology department is part of the standard care protocol, which also includes a systematic reevaluation 4 -6 months following the surgical intervention.

Predicting the outcome of pituitary surgery, particularly the risk of complications, is a critical determinant in selecting the appropriate treatment modality for patients. To date, only a limited number of risk factors have been identified for complications following pituitary surgery, including tumor size, younger age, and previous surgical intervention. Furthermore, existing studies have demonstrated that prolactin levels can serve as a surrogate marker for assessing pituitary function, specifically revealing associations between elevated prolactin levels and anterior pituitary insufficiencies.

In a retrospective study on the "HYP'OP" cohort, the aim of the study is to identify predictive factors for both surgical outcomes and complications.

Prognostic Indicators in Pituitary Adenoma Surgery: a Comprehensive Analysis of Surgical Outcomes and Complications.

Patients were stratified into four groups using the same criteria as outlined in Outcome 3.

Risk factors associated with complications arising from surgery, specifically targeting the incidence of de-novo, clinically significant pituitary insufficiencies

Patients were stratified into groups based on surgical indications. The first group consisted of non-secreting, non-compressive adenomas without preoperative insufficiency or hyperprolactinemia, with success defined as absence of new insufficiency and no MRI-detected residual tissue. The second group was similar to the first but included disconnection hyperprolactinemia, and success was defined by the absence of new insufficiency and hyperprolactinemia regression. The third group involved non-secreting adenomas with at least one preoperative axis deficiency, irrespective of hyperprolactinemia, with success defined as restoration of at least one deficient axis without new insufficiency. The fourth group included secreting adenomas, with success defined as hypersecretion regression. The fifth group involved adenomas operated on for their compressive effect on the optic pathways, with or without hyperprolactinemia, and success was defined as no compression observed on follow-up MRI.

patients were stratified into four groups based on immediate postoperative prolactin levels: Group 1 consisted of severe hypoprolactinemia; Group 2 included moderate hypoprolactinemia; Group 3 involved normal prolactin levels, defined by prolactin levels between 5 and 20 ng/ml; and Group 4 comprised hyperprolactinemia, defined by prolactin levels \> 20 ng/ml. It should be noted that these instances of hyperprolactinemia are theoretically all disconnection hyperprolactinemias, as patients with lactotroph adenomas were excluded from this analysis. Patients under treatment for hyperprolactinemia were also excluded.

Central Hospital, Nancy, France

Principal Investigator

Central Nervous System Depressants

Platelet Aggregation Inhibitors

Other Dietary Supplements

Anesthetics

Propofol

Sevoflurane

Benzocaine

Hypnotics and Sedatives

Anesthetics, Intravenous

Anesthetics, General

Anesthetics, Inhalation

Tannic Acid

Anesthesia is maintained with sevoflurane.

Anesthesia is maintained with continuous infusion of propofol.

Anesthesia is maintained with inhalation of sevoflurane. The concentration of sevoflurane was adjusted to maintain anesthetic depth, aiming for a bispectral index of 40-60.

sevoflurane

Anesthesia is maintained with an effect-site target-controlled infusion of propofol (2-6ug/ml) based on the Marsh mode. The concentration of propofol was adjusted to maintain anesthetic depth, aiming for a bispectral index of 40-60.

propofol

Lulu Ma, MD

Yunying Feng, MDc

Yuguang Huang, MD

Bing Xing, MD

Wei Lian, MD

Currently, total intravenous anesthesia (TIVA) and inhaled anesthesia are both commonly used for transsphenoidal pituitary adenoma resection. However, optimal choice for anesthesia maintenance in transsphenoidal surgery remains unclear. Previous studies focusing on this question provided fragmentary assessment and controversial results. The goal of this clinical trial is to investigate whether propofol and sevoflurane have different effect on post-anesthetic recovery after transsphenoidal resection of pituitary adenoma.

Comparison of Postoperative Recovery of Sevoflurane and Propofol After Transsphenoidal Surgery

A Prospective, Randomized Controlled Study to Compare the Effect of Sevoflurane and Propofol for Maintenance of Anesthesia on Postoperative Recovery After Transsphenoidal Resection of Pituitary Adenoma

The investigators record major postoperative complications and other complications related to anesthesia not mentioned above.

The investigators record major postoperative complications and other complications related to surgery and anesthesia by telephone follow-up.

The investigators record NRS pain score (0 to 10, higher the more painful) of patients on the 7th day after the surgery by telephone follow-up.

Score: 0, no nausea and vomiting; 1-4, mild nausea and vomiting; 5-6, moderate nausea and vomiting; 7-10, severe nausea and vomiting.

The investigators record the sleep quality score (0 to 10, higher the better) of patients on the 7th day after the surgery by telephone follow-up.

The investigators record the appetite score (0 to 10, higher the better) of patients on the 7th day after the surgery by telephone follow-up.

The investigators record the patients' readmission to our hospital due to any pathological reason (to outpatient or inpatient).

The investigators examine the serum level of cortisol in ug/dL.

The investigators examine the serum level of GH in ng/mL.

The investigators examine the serum level of gonadotrophin in IU/L.

The investigators examine the serum level of TSH in uIU/mL.

The investigators examine the serum level of PRL ng/mL.

The QoR-15 score ranges from 0 to 150 (higher is better). The investigators record the scores of two groups 1 day after the surgery.

The time between discontinuing drugs and response to verbal command.

The time between discontinuing drugs and withdrawal of tracheal tube.

The highest Richmond agitation and sedation scale score (RASS) during emergence. The RASS score ranges from -5 to +4, and a lower score indicates a more sedative level.

Coughing score ranges from 0 to 3, and a higher score indicates a severer outcome.The investigators record the highest coughing score during emergence.

The time between admission into PACU and discharging from PACU with Aldrete score over 9. Aldrete score ranges from 0 to 10, and a higher score indicates a better recovery from anesthesia.

The drug use due to postoperative nausea and vomiting in PACU.

The drug use due to postoperative pain in PACU.

The investigators examine the serum level of ACTH in pg/mL.

Hypotension is defined as decrease of mean arterial pressure (MAP) more than 20% of baseline.

Hypertension is defined as increase of MAP more than 20% of baseline.

The time between end of surgery and discharge from hospital.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Feasibility of Endosphenoidal Coil Placement for Imaging of the Sella During Transsphenoidal Surgery	NCT03678389	Pituitary Neopl...	ESC	18 Years - 85 Years	National Institutes of Health Clinical Center (CC)
Feasibility of Endosphenoidal Coil Placement for Imaging of the Sella During Transsphenoidal Surgery	NCT03678389	Pituitary Neopl...	ESC	18 Years - 85 Years	National Institutes of Health Clinical Center (CC)
Transsphenoidal Extent of Resection Study	NCT02357498	Pituitary Adeno...	transsphenoidal...	18 Years - 80 Years	St. Joseph's Hospital and Medical Center, Phoenix
Transsphenoidal Extent of Resection Study	NCT02357498	Pituitary Adeno...	transsphenoidal...	18 Years - 80 Years	St. Joseph's Hospital and Medical Center, Phoenix
Surgical Debulking of Pituitary Adenomas	NCT01371643	Pituitary Adeno...	Octreotide LAR transsphenoidal...	18 Years -	NYU Langone Health
Prognostic Indicators in Pituitary Adenoma Surgery: a Comprehensive Analysis of Surgical Outcomes and Complications.	NCT06053437	Pituitary Adeno... Surgery-Complic...		18 Years -	Central Hospital, Nancy, France
Comparison of Postoperative Recovery of Sevoflurane and Propofol After Transsphenoidal Surgery	NCT05822817	Pituitary Adeno...	sevoflurane propofol	18 Years - 70 Years	Peking Union Medical College Hospital
Surgical Debulking of Pituitary Adenomas	NCT01371643	Pituitary Adeno...	Octreotide LAR transsphenoidal...	18 Years -	NYU Langone Health

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