Endoscopic Endonasal Trans-Sphenoidal Minimally Invasive Pituitary Surgery with Image Guided Navigation System (Igns): Learning Experience of Ent Surgeon

Abstract

Introduction- Endoscopic minimally invasive pituitary surgery (MIPS) is advantageous over microscopic technique, as it provides superior close up, wide angle view of surgical target area. Image guided navigation system (IGNS) guides the surgeon to localize the lesion. In the present study we analyzed the Image Guided Surgical procedure and outcome of Endoscopic minimally invasive pituitary surgery and shared our experiences regarding disease clearance.

Materials and methods: During the period of April 2015 to August 2022 a total 104 patients, diagnosed with pituitary adenoma underwent surgery and further followed up in a multidisciplinary team approach in a tertiary care hospital of Kolkata, India. The data obtained were reviewed statistically to satisfy the study objectives.

Results: Total 104 operations were done on 98 patients and total cases taken for calculation and analysis was 98, which consist of 11 microadenomas, 81 macroadenomas. Among 35 patients with normal preoperative hormonal assay, one patient developed postoperative hypopituitarism. Among 6 patients with preoperative hypopituitarism 4 patients (66.6%) recovered after surgery. Overall, 85 cases had total disease clearance as detected on post-operative MRI. In functioning pituitary adenoma (FPA) clinical and endocrinological improvement occurred after primary surgery in 85.36% (n = 35) and after revision surgery it was 84.44% (n = 38). Macroadenomas, giant adenomas were found to have statistically significant higher risk of incomplete disease clearance but large adenomas do not have statistically higher risk of incomplete clearance.

Conclusion: IGNS requires extra time for setup, but with proper registration of tracker instruments it adds precision to the surgery. IGNS supplements endoscopic visualization with localization of target lesion by real time stereotactic feedback using preset preoperative imaging data, thus increasing accuracy, safety and effectiveness of minimally invasive surgery.

Introduction

Technological advancements caused a paradigm shift in the field of endoscopic skull base and sinus surgery. Devices like a navigation system along with endoscopes and high-definition camera, microdebrider, drill and coblation devices allow us to work in the narrow corridor of anterior skull base surrounded by neurovascular structures. Overall progress in the field of radiology, endocrinology, ophthalmology, otorhinolaryngology, anesthesiology, neurosurgery and pathology has greatly improved multidisciplinary approach to pituitary disorders and it is evident from decreasing morbidity and mortality in pituitary tumor surgery.

Endoscopic Minimally Invasive Pituitary Surgery (MIPS) is advantageous over microscopic technique, as it provides superior close up wide angle view of surgical target area approached through nasal passage [1]. The operative technique consists of exposure of lesions (Nasal and Sphenoid phases), removal of tumor and repair of surgical defect (Sellar phase) [1]. This technique enables minimal mucosal injury, less postoperative pain, no or light nasal packing, quick recovery, short postoperative hospital stay and lower morbidity and mortality [2].

Image Guided Navigation System (IGNS) guides the surgeon to localize the lesion with the tracker instrument tip over the preloaded preoperative CT scan or MRI images in DICOM format. IGNS influences the surgical procedure positively. Although it prolongs the operative time, IGNS lowers intraoperative blood loss, lowers complications rate and reduces number of revision surgeries [3–5]. Electromagnetic (EM) IGNS is preferred by most surgeons [6]. In the present study we analyzed the Image Guided Surgical procedure and outcome of Endoscopic MIPS and shared our experiences regarding disease clearance in our operated cases.

Materials and Methods

A retrospective observational study was done at the Department of Otorhinolaryngology, at a tertiary care hospital in India from the period of April 2015- August 2022. During this period a total 104 patients with diagnosed pituitary adenoma underwent surgery done by a combined team of ENT and neurosurgeon with active involvement from the Departments of Endocrinology, Radiology, Ophthalmology and Pathology of the same Institute. Patients preoperative, perioperative and post-operative data were collected along with data of systematic follow-up at 2 weeks, 4 weeks, 3 months and 6 months respectively.

The Inclusion criteria of participants of our study were:

1. MRI and CT scan proven pituitary macroadenoma.

2. Pituitary microadenoma cases in which medical management was unsuccessful.

Pre-operative MRI was done to diagnose and assess the tumor size, extent, involvement of adjacent neurovascular structures and relevant anatomy of nose and paranasal sinuses. The findings were corroborated with Nasal Endoscopy. Contrast enhanced CT scan was done in Neuro-navigation Sellar protocol (1 mm triplanar cuts) with the data stored in CD / DVD in DICOM format and was loaded on Fusion Navigation system, Medtronic™ [7]. All patients underwent endocrinological evaluation. Hormonal analysis consisting of serum Cortisol, GH and IGF 1, Prolactin, FSH, ACTH, LH, FT4 and TSH. Testosterone (in males) and Estradiol (In female) was assessed. These hormonal levels were checked post operatively at regular intervals. Pre-operative and post-operative ophthalmological evaluation of acuity of vision, field of vision and complete neurological evaluation was done. All patients were admitted in Otorhinolaryngology wards. Informed consent was taken from each patient after explaining the risk- benefit of the procedure. Post operatively all patients were kept in the Intensive Care Unit for close monitoring by the team. Nasal packing was removed after 48 h in the post-operative period and oral feeds started. Patients were discharged between 5 and 7 days and advised for the next follow up after 2 weeks.

IGNS (Fig. 1): The navigation system is a surgical guidance platform. It supports use of special application software and associated instruments. The system reformats patients specific CT or MRI images acquired before surgery and displays them on monitors in axial, coronal and sagittal planes in real time. During surgery, the system simultaneously tracks the patient’s anatomy and registered surgical instruments. Once the surgeon completes the registration task in the software, the system creates a translation map between all the points in the patient’s images and the corresponding point on the patient’s anatomy. After establishing this map, wherever the operator touches a point on the patient with a registered instrument with tracker attached, the computer uses the map to identify the corresponding point in the radiological images. This identification is called navigation or localization.

Fig. 1.

Real time endoscopic image with localization in triplaner cuts in MRI

Transsphenoidal pituitary surgery requires understanding of complex regional neurovascular anatomy and bony landmarks and demands high precision in surgery. Precision surgery becomes more challenging if anatomical landmarks are obscured by previous surgery or if disease invades and engulfed the surrounding structures. Both CT scan (for bony landmarks and integrity) and MRI (for soft tissue differentiation) are done as per navigation protocol and accordingly either may be used independently or fused as per requirement for that case.

Surgical Technique: This includes 6 stages (Figs. 2, 3, 4 and 5).

Fig. 2.

Giant pituitary macroadenoma with suprasellar extension and cavernous sinus invasion; sagittal sections (a), coronal sections (b), IGNS registration of tracker (c), Incision (d)

Fig. 3.

Exposure of Rostrum of sphenoid (e), Bone removal from anterior wall of sella by drilling (f) and Kerrison punch (g), Exposure of dura (h)

Fig. 4.

Bipolarization of dura (i), Exposure of macroadenoma after creation of dural “U” flap (j), resection of macroadenoma (k, l)

Fig. 5.

Inside tumour cavity following total tumour resection (m, n), Descend of meningeal dura (o), filling of tumour cavity with surgical and tissue glue (p)

• I.Nasal Stage: It consists of assessment of endoscopic anatomy of nose and surgical exposure of the sphenoid ostium. We prefer to operate through the left nostril unless gross DNS to the left is present. We performed surgeries mainly by mono-nostril approach in two-handed technique; and bi-nostril approach in four-handed technique was done in selected circumstances only.

• II.Sphenoid stage: The posterior most part of the nasal septum is pushed to the opposite side and fractured. Mucosa around contralateral sphenoid ostium is lifted which exposes the characteristic “owl’s eye” appearance of the anterior face of sphenoid. A wide anterior sphenoidotomy is done, which creates a direct surgical corridor.

• III.Sellar stage: Anatomical landmarks are identified keeping the Sella in the center and imaging the sphenoid as a dial of a clock. The following anatomy are noted:

At 12 O’ clock is tuberculum sellae and at 6 O’ clock lies the clivus.

At 11 and 1 O’ clock positions are the optic nerves.

At 10 and 2 O’ clock positions are right and left paraclinoid carotids.

Between 10 and 8 O’ clock position on the right and 2 to 4 O’ clock position on the left are cavernous carotids.

At 7 and 5 O’ clock positions are right and left paraclival carotids.

IGNS helps confirm the presumed landmarks.

Now the mucosa overlying sella is bipolarized and removed. The surgical limits around sella are mapped by the navigation probe. The sellar floor is egg-shelled by gentle low speed drilling using a 3 mm diamond burr and broken using a circular knife. By gentle inward pressing of sella dura estimation of circumferential bone removal can be done. The bone is removed millimeter by millimeter using 1 mm Kerrison punch very gently laterally up to the cavernous sinuses and superiorly and inferiorly up to intercavernous sinuses. For large tumors with suprasellar extension an extended approach (Transplanar/ Transtuberculum) is undertaken.

• IV.Dural stage: Using a no. 11 surgical blade a ‘Y’ or ‘U’- shaped incision is placed on the dura and it is dissected and peeled away from the tumor. If any bleeding is encountered, it is bipolarized.
• V.Tumor Removal: Once the tumor is exposed a biopsy sample is collected for histopathological examination. Tumor excision may be done in an intra/ extracapsular fashion. Tumor decompression is done concentrically starting at the basal part, followed by lateral part and last the superior part of tumor is removed using different ring curette and suction. The compressed normal pituitary plastered to diaphragmatic sella is seen as a pinkish tissue is identified and preserved. But extracapsular removal ensures better tumor removal and is usually favored. In this technique only the outer layer of dura is cut and excised keeping the inner layer intact; followed by all around dissection of the capsule. IGNS plays an important role in dictating the extent of tumor removal and preventing the surgeon from injuring the prolapsing anatomical boundaries.

At the end of the surgery descended diaphragma sella is pushed up with a suction tip. An intervening cotton patty is placed and the tumor cavity is inspected with a 30^o nasal endoscope (Karl Storz, Germany) stationed at 6 0’ clock position. The endoscope is rotated all around for thorough inspection. The common sites of retained tumor are at medial optico-carotid recess (MOCR) and under the anterior lip of dura at or above the level of anterior intercavernous sinus. IGNS is indispensable in guiding the surgeon in these hidden areas. After satisfactory tumor removal the Anesthesiologist doctor is asked to perform a Valsalva maneuver on the patient to exclude CSF leak.

• VI.Reconstruction: If there is no CSF leak and requisite hemostasis done, the sellar cavity is closed (except in microadenoma) using fat/ gelfoam/ surgical/ tissue glue. But an overzealous sellar packing is discouraged. Minor CSF leaks can be sealed with fat and tissue glue (TISSEL, Baxter AG, Vienna, Austria). Larger leak is closed with Hadad- Bassagasteguy flap, a pedicled vascularized septal flap or by a multilayer repair. Middle turbinate is then medialized and the Merocel (Medtronic, Minneapolis, USA) nasal pack is placed in the middle meatus.

Disease control: It means total removal of Tumor in Non-Functioning pituitary adenoma (NFPA) and remission of hormonal imbalance with improvement of clinical features in Functioning pituitary adenoma (FPA). To assess this, a hormonal panel for Pituitary is done at the end of 6 weeks; MRI and automated perimetry is performed at 3 months.

Our criteria for postoperative remission of FPA are as follows,

• aProlactinoma – Serum Prolactin < 20 ng/ml at the end of 6 weeks and improvement of clinical condition.
• bAcromegaly – Normalization of IGF 1 level and nadir GH level (< 1 µg/l) after OGTT, at the end of 6 weeks and improvement of clinical condition.
• cCushing’s disease – Normalization of 8 AM cortisol level and 24 h urinary free cortisol along with overnight dexamethasone suppression test; along with resolution of clinical features.

Statistical Analysis

All data analysis was done using IBM SPSS statistics, version 26.0 (IBM Corp., Armonk, NY, USA) and comparative analyses were completed. The tumor diameter in patients with preoperative and post-operative MRI, improvement in preoperative symptoms (Headache, Visual impairment, features of hormonal changes) after surgery were assessed using Chi-square and Fisher exact test. Prediction parameters for disease clearance in Pituitary tumors was assessed. Comparative statistical analysis between different tumor sizes, tumor extension and primary/ revision surgery was done using standard statistical tests. A p-value < 0.05 was considered statistically significant.

Results

Present study consists of 98 patients among which 42.86% (n = 42) were male and 57.14% (n = 56) were female. The age distribution of the patients was between 18 years to 73 years (median age 49.3 years). Majority of the patients were between the 31–40 years age group (47.96%, n = 47) and only one patient (1.02%) was under 20 years of age. The other patients were in the 41–50 years age group (27.55%, n = 27), 21–30 years age group (17.35%, n = 17) and above 50 years age group (6.12%, n = 6). These patients underwent navigation guided endonasal transsphenoidal minimally invasive pituitary surgery by the same surgical team over a period of 8 years. Total 104 surgeries were performed (98 primary cases & 6 revision cases). 6 patients were lost to follow up.

Tumor size according to maximum diameter was grouped into microadenoma (< 10 mm; 11.22%; n = 11) and Macroadenoma (> 10 mm; 88.78%; n = 81). Macroadenoma > 20 mm in maximum diameter was denoted as “Large” and > 30 mm in maximum diameter was denoted as “Giant”.

In the study population 11.22% (n = 11) patients had microadenoma, 82.65% (n = 81) macroadenoma and 6.13% (n = 6) macroadenoma requiring revision surgery. Total 54.08% (n = 53) were non-functional pituitary adenoma (NFPA) and rest functional pituitary adenoma (FPA) (45.92%; n = 45). FPA were prolactinoma (n = 19; 42.22%), Somatotrophadenoma (n = 19; 42.22%) and ACTH-oma (n = 7; 15.56%).

Preoperative MRI detected tumors in all the patients, macroadenoma (n = 87, 100%) and microadenoma (n = 11, 100%). The mean diameter of Macroadenoma was 22 mm (range 11-38 mm). Suprasellar extension (SSE) was present in 13.27% (n = 13) patients. Cavernous sinus invasion (CSI) was present in 10.20% (n = 10) patients. Combined SSE + CSI was present in 10.20% (n = 10) cases. Sellar floor destruction and extension of lesion into Sphenoid sinus was present in 7.14% (n = 7) patients.

Preoperative ophthalmological examination revealed decreased visual acuity in 17.35% (n = 17) patients and blindness in both eyes in 2 (2.04%) patients. Automated perimetry diagnosed superior quadrantanopia in 6.12% (n = 6) patients and bitemporal hemianopsia in 9.18% (n = 9) patients. Overall, 19.39% (n = 19) patients had visual impairment of different degrees.

Hormonal parameters were normal in 35.71% (n = 35) patients. Raised serum Prolactin (19.39%), IGF1 & GH (19.39%), Cortisol (7.14%), hypothyroidism (15.31%), hypogonadism (11.22%), Panhypopituitarism (6.12%) were found in hormonal studies and examination.

Preoperative assessment of the study population has been tabulated in Table 1.

Table 1.

Preoperative assessment

	Total (n = 98)	NFPA (n = 53)	Prolactinoma (n = 19)	GH-oma (n = 19)	ACTH-oma (n = 7)
Preoperative symptoms
Headache	59	42	03	11	03
Visual Impairment	29	21	03	05	0
Features of Hormonal Changes	62	17	19	19	07
Preoperative Examination
Imaging
Microadenoma (< 10 mm)	11	0	4	0	7
Macroadenoma (> 10 mm)	81	51	13	17	0
Large Adenoma (21–30 mm)	30	20	2	8	0
Giant Adenoma (> 30 mm)	12	9	0	3	0
Suprasellar extension (Wilson-Hardy B,C,D)	13	10	0	3	0
Cavernous Sinus Invasion (KNOSP 2,3,4)	10	5	2	3	0
Combined SSE + CSI	10	7	0	3	0
Sellar floor Destruction & Sphenoid extension	7	5	0	2	0
Endocrinological
Raised Prolactin	19	0	19	0	0
Raised IGF1 & GH	19	0	0	19	0
Raised Cortisol	7	0	0	0	7
Hypothyroidism	15	10	0	02	3
Hypogonadism	11	3	4	01	3
Hypopituitarism	6	4	1	01	0
Ophthalmological
Decreased Visual Acuity	17	12	2	5	0
Superior Quadrantanopia	6	5	1	0	0
Bitemporal Hemianopia	9	7	0	2	0
Blindness	2	2	0	0	0
Revision surgery	6	2	2	2	0

Findings regarding operative time taken, per-operative difficulties and post-operative complications encountered in our study are charted in Table 2.

Table 2.

Per-Operative and Post-operative assessments

	Total (n = 98) %	NFPA (n = 53) %	Prolactinoma (n = 19) %	GH-oma (n = 19) %	ACTH-oma (n = 7) %
Operative time
< 2 h	14	8	3	1	2
2–3 h	53	29	12	7	5
3–4 h	23	11	4	8	0
> 4 h	8	5	0	3	0
Per Operative difficulties
Hemorrhage < 100 ml	57	28	14	8	7
Hemorrhage > 100 ml	41	25	5	11	0
CSF Leak	5	3	0	2	0
Post-operative complications
Transient Diabetes Insipidus	5	3	1	1	0
CSF Rhinorrhea	2	1	0	1	0
Meningitis	1	1	0	0	0
Hypopituitarism	3	3	0	0	0
Hyponatremia	5	3	0	2	0
Epistaxis	1	0	0	1	0
Internal Carotid artery Injury	0	0	0	0	0
Loss of vision	0	0	0	0	0
Sphenoid Sinusitis	0	0	0	0	0
Nasal synechia	0	0	0	0	0
Anesthetic Complications	0	0	0	0	0
Residual Tumor	6	2	2	2	0

7.14% (n = 7) patients experienced surgical complications. Transient diabetes insipidus and transient hyponatremia occurred in 5.10% (n = 5) patients. Two patients (2.04%) developed CSF rhinorrhea; among them one patient (1.02%) developed meningitis subsequently. Both the patients recovered completely with conservative treatment. Post-operative hypopituitarism developed in 03 patients (3.06%). Median postoperative hospital stay of the patients was 5.7 days (range 4–21 days). 89.80% (n = 88) patients were discharged on day 7 postoperatively. No case of Carotid artery injury, iatrogenic visual loss, post-operative sinusitis and synechia occurred in our series.

Residual tumor was detected in post-operative MRI of 10 (10.20%) patients after first surgery (5 NFPA, 2 Prolactinoma, 3 GH-oma). Among 10 patients 6 patients underwent revision surgery (6.12%). 17(18.48%) patients with prolactinomas underwent preliminary surgery; total tumor removal was achieved in 15 (88.24%) patients among them documented by post-operative MRI and Serum prolactin level. 2 (15.38%) patients with prolactin secreting macroadenoma required revision surgery and one (25%) patient with prolactin secreting microadenoma was treated with dopamine agonist, though MRI showed no postoperative residual tumor in that case.

Primarily 17 (18.47%) patients had GH-oma & acromegaly. Total tumor removal after primary surgery was done in 14(82.35%) patients. 2(11.76%) patients required revision surgery, and after revision surgery hormonal parameters were corrected and clinical features of acromegaly improved.

7 (7.14%) patients with ACTH – microadenoma (Cushing’s disease) were operated on. Complete disease remission was observed in 5 (71.43%) patients with normalized cortisol level. Postoperative MRI detected no adenoma in all 7 patients. But in the other two patients’ cortisol level remained high. These two patients later underwent laparoscopic bilateral adrenalectomy and cortisol level subsequently became normal.

Among 35 patients with normal preoperative hormonal assay one (2.86%) patient developed postoperative hypopituitarism, which improved later and among 6 patients with preoperative hypopituitarism 4 (66.6%) patients recovered after surgery.

Postoperative MRI was performed 6 weeks after primary surgery and detected residual tumor in 5 (9.43%) cases of NFPA and no residual tumor in 48 (90.57%) cases of NFPAs (p < 0.001). Frequency of preoperative complaints such as headache, visual impairment, and signs symptoms of hormonal changes improved significantly at 3 months or more after surgery. 84.75% (n = 50) patients had improvement or complete resolution of headache (p < 0.001). 93.10% (n = 27) patients had improvement or normalization of vision (p < 0.001); 80.39% (n = 41) had betterment of hormonal derangement (p < 0.001). (Fig. 6)

Fig. 6.

Pre-operative & 3 month post-operative comparative frequency distribution of headache, visual impairment & Hormonal changes

Patients quantified nasal discomforts 3 months post-operatively after primary surgery. They are as follows: nasal airway obstruction – none 89.80% (88), mild 8.16% (8), moderate 2.04% (2); loss of smell-none 96.94% (95), mild 3.06% (3); nasal congestion- none 81.63% (80), mild 13.26% (13), moderate 5.11% (5). (Fig. 7)

Fig. 7.

Post-operative nasal discomfort after 3 months

After primary surgery patients were allowed to start their normal daily activities one month after surgery and 87.76% (n = 86) patients returned to normal activities by 3 months after surgery. Patients who could not return to normal daily activities are as follows: Patients requiring revision surgery (n = 6), Cushing’s disease requiring bilateral adrenalectomy (n = 2), hypopituitarism (n = 3), Postoperative CSF rhinorrhea with meningitis (n = 1).

Histopathological examination revealed eosinophilic adenoma (64.13%, n = 59), basophilic adenoma (7.60%, n = 47 and chromophobe adenoma (28.26%, n = 26) in our series.

Overall, 85 (86.73%) cases had total disease clearance as detected on post-operative MRI, of which 12.94% (n = 11) were microadenoma, 83.53% (n = 71) were macroadenoma and 5.17% (n = 3) were revision of macroadenoma. All microadenomas had total disease clearance (n = 11). 50% of revision surgeries had total disease clearance (n = 3) and 87.65% of macroadenomas had total disease clearance after primary surgery (n = 71). (Table 3)

Table 3.

Total disease clearance

	Total disease clearance (n = 85) (%)	NFPA (n = 46) n(%)	Prolactinoma (n = 15) n(%)	Acromegaly/ GH-oma (n = 14) n(%)	Cushing’s/ ACTH-oma (n = 7) n(%)
Microadenoma( < = 10 mm)	11(11.11)	0	4(18.18)	0	7(100)
Macroadenoma(> 10 mm)	71(83.83)	46(100)	11(63.63)	14(90)	0
Revision surgery	3(5.55)	0	2(18.18)	1(10)	0
Large adenoma(21-30 mm)	25(27.77)	19(37.93)	0	6(40)	0
Giant adenoma(> 30 mm)	7(3.70)	5(6.89)	0	2	0
Suprasellar extension	10(12.9)	8(17.24)	0	2(20)	0
CSI	7(7.40)	4(6.89)	1	2(20)	0
SSE + CSI	7(5.55)	5(6.89)	0	2(10)	0
Sellar floor destruction & Sphenoid extension	6(5.55)	5(10.34)	0	1	0

Disease clearance for macroadenoma < 20 mm was better (100%, n = 39) compared to large and giant adenoma (76.19%, n = 32). If combined suprasellar extension and cavernous sinus invasion were present (n = 10) the disease clearance was reduced to 70% (n = 7). In macroadenoma with suprasellar extension (SSE) disease clearance was 76.42% (n = 10) and with cavernous sinus invasion (CSI) only disease clearance was 70% (n = 7).

In nonfunctioning pituitary adenoma (NFPA) postoperative residual tumor detected by MRI after primary surgery in 9.80% (n = 5) cases out of 51 patients; among them one each of SSE and CSI and 03 cases had combined SSE and CSI. Preoperative hormonal impairment was present in 32.07% (n = 17) patients; it normalized or improved in 82.35% (n = 14) patients and remained unchanged in 17.65% (n = 3) patients.

In functioning pituitary adenoma (FPA) clinical and endocrinological improvement occurred after primary surgery in 85.36% (n = 35) and after revision surgery it is 84.44% (n = 38). Remission of clinical and endocrinological parameters were better in smaller (< 20 mm) adenomas. No endocrinological remission in 5 patients (50%) with combined SSE & CSI and 2 (20%) patients with only CSI.

The surgical outcome of pituitary tumors of different tumor size (micro/ macro/large/giant adenoma), disease extension (SSE/ CSI/ SSE + CSI/Sellar floor destruction) and revision surgeries were compared to the total number of primary cases (n = 85) that have total disease clearance to evaluate which factor can be used as dependable predictive parameter for incomplete disease clearance. (Table 4)

Table 4.

Prediction parameters for disease clearance in Pituitary tumor (Different tumor size, disease extent, primary/secondary surgery are compared to Outcome of all cases in the study)

	Odds Ratio	95% Confidence Interval	P-value (< 0.05 considered significant)
Microadenoma( < = 10 mm)	0.36	0.01–6.93	0.5
Macroadenoma(> 10 mm)	0.87	0.32–2.35	0.78
Large adenoma(21-30 mm)	0.98	0.24–3.9	0.97
Giant adenoma(> 30 mm)	12.27	2.1–71.5	0.005
Suprasellar extension (SSE)	0.701	0.07–6.28	0.75
Cavernous Sinus Invasion (CSI)	2.45	0.39–15.1	0.33
SSE + CSI	4.9	0.87–27.5	0.07
Sellar floor destruction & Sphenoid extension	1.63	0.15–17.23	0.68
Revision surgery	4.9	0.87–27.5	0.07

Microadenoma, macroadenoma (> 10 mm to < 30 mm) and cases with SSE had higher association with total disease clearance. Giant adenoma (> 30 mm), cases with CSI, combined SSE & CSI, sellar floor destruction and revision surgeries have higher association of incomplete disease clearance. In a nutshell all cases of macroadenoma did not have statistically significant higher risk of incomplete clearance but giant adenomas have statistically significant higher risk of incomplete clearance (p < 0.005).

Comparative statistical analysis between different tumor sizes, tumor extension and primary and revision surgery (Table 5) reveals: among macroadenomas, giant adenomas have statistically significant higher risk of incomplete disease clearance (p < 0.005) but large adenomas (21-30 mm) do not have statistically higher risk of incomplete clearance. Revision surgeries have statically higher risk of incomplete disease clearance (p < 0.05) than cases operated for the first time. Macroadenoma and cases with CSI have no statistically significant association with incomplete disease clearance compared to microadenoma and cases with SSE respectively.

Table 5.

Comparative statistical analysis between different tumor sizes, tumor extension and primary/ revision surgery

	complete disease Clearance	Incomplete disease clearance	Odds Ratio	95% Confidence Interval	P-value
Macroadenoma v/s Microadenoma	71	10	0	0- Undefined	0.62
	11	0
Macroadenoma v/s Giant adenoma	71	10	5.071	1.348–19.077	0.022
	7	5
Macroadenoma v/s Large adenoma	71	10	1.420	0.442–4.558	0.544
	25	5
Large adenoma v/s Giant adenoma	25	5	3.571	0.800–15.947	0.117
	7	5
SSE v/s CSI	10	3	1.429	1.454–46.241	1.000
	7	3
Primary surgery v/s Revision surgery	82	10	8.2	1.454–46.241	0.029
	3	3

Discussion

Pituitary surgery has witnessed a sea change as the newer technologies and techniques evolve. The endoscopic endonasal minimally invasive pituitary surgery has now unsettled the traditional sublabial/ transseptal microscopic technique [8, 9]. When performed in conjunction with IGNS the overall accuracy in defining the anatomical landmarks are greatly enhanced [10–13].

Advantages of IGNS are:

1. Anatomical guidance to surgeon in cases with anatomical variations, revision cases, proximity to ICA and Optic nerve- Sellar and Dural phases.

2. Surgical accuracy, especially when expanded trans-sphenoid technique are undertaken.

3. Improves surgeon’s confidence and proficiency, which speeds up the learning curve and also an important teaching tool for juniors.

4. IGNS has a distinct advantage over fluoroscopy as it provides continuous, multiplanar 3D imaging without exposure to radiation hazards.

5. Accurate and quick localization of target lesion by visualization of triplaner images even when bleeding obscures the endoscopic visualization of surgical field.

There are certain limitations of IGNS:

1. High equipment cost and with rapid progress in technologies these high end platforms become obsolete unless upgraded.

2. Setup time increased, which prolongs total operative time.

3. It requires more space in the operation theater.

4. Target registration error (TRE), that gives spurious localization; if unrecognized by the surgeon, then the result may be catastrophic.

5. IGNS use preoperative data only but per-operative dynamic changes in the surgical field due to tissue shift produces inaccuracy.

6. Image guided endoscopy can only be done with rigid endoscopes at present and thus only a linear approach for trajectories can be done.

IGNS is used by surgeons to achieve better surgical results. IGNS is associated with lower intraoperative blood loss [4, 14]. The number of revision surgeries is reduced when IGNS is used [5]. But Cappabianca and colleagues found no significant improvement in mortality and morbidity in revision Endoscopic pituitary surgery with the use of IGNS [15] though they had shorter surgery time and better efficiency. In a study conducted by Strauss et al. [16] showed use of IGNS resulted in intraoperative change in surgical decision making. A major meta-analysis by Dalgorf et al. [17] shows IGNS is associated with fewer major and minor complications.

Accuracy of IGNS directly depends upon target registration error. In various published reports the mean TRE (Target registration error) ranges between 1.5 and 2.3 mm [18]. The bottom line is, IGNS is useful quite often but prevalence of high TRE (i.e., inaccuracy) limits its usefulness. TRE value > 2 mm adversely affects IGNS utility.

In our experience of endoscopic endonasal MIPS under image guidance provides the surgeon a wide-angle close up view of the surgical field, better visualization in and around the target areas; broad lateral vision identifies important neurovascular structures and further enhanced by IGNS. Better visualization and identification of neurovascular structures lowers complications. Use of angled endoscopes readily shows sellar and suprasellar structures which are away from straight view. Though endoscope provides 2D image, use of IGNS enhances depth perception in triplaner sections. IGNS supplements a surgeon’s knowledge of surgical anatomy. Tumor removal is better due to localization and visualization of target lesion and inadvertent injury to normal pituitary gland is minimal. We found IGNS is particularly helpful in localizing target areas in case of microadenoma, difficult sphenoid anatomy and revision surgery. Fusion navigation system (Medtronic Inc USA) can fuse CT and MRI images and create a composite hybrid image which depicts surrounding bony and soft tissue anatomy in a single frame [7]. Fusion IGNS facilitates more comprehensive MIPS with low morbidity.

As the surgery is done by endonasal direct sphenoidotomy approach without any nasal or gingival mucosa traumatization; nasal or sinus complication are negligible and that is why revision surgery if required is easier to perform in absence of any scar or adhesion. With total tumor removal, pituitary gland function improves along with improvement of visual improvements and other sign-symptoms. Endoscopic endonasal MIPS has minimal complications and quick recovery occurs to the patients compared to microsurgical transsphenoidal series like that of Ciric et al. [19]. Final outcome depends on localization and visualization of surgical target, tumor removal, biology of adenomas and preservation of surrounding neurovascular structures [20, 21].

Future development in Image guided endoscopic surgery will come with optimization of the next generation system with better accuracy. Reduction of target registration error around 1.0 mm should be feasible. With miniaturization of equipment, the future IGNS is expected to have smaller footprints. Semi-autonomous or autonomous surgical robots incorporating IGNS have already been developed [22]. A novel transantral robotic endoscopic skull base surgery in cadavers has been developed [23]. For a non-linear approach to target lesion, flexible IGNS tracked endoscopes will be useful. Ultimately image guided endoscope with head mounted display is likely to end the era of microscopic surgery [23].

Otorhinolaryngologists perform a large number of endoscopic endonasal surgery routinely, though they do endoscopic pituitary surgery infrequently. Some studies suggested performing 40–80 endoscopic pituitary surgery to grow the surgical skill [24, 25]. Proficiency in nasal endoscopy is directly proportional to reduction in post-operative nasal morbidity. Neurosurgeons play a leading role in endoscopic pituitary surgery worldwide. Neurosurgeons were an active part of the surgical team performing cadaver dissection and in the first 10 cases of Pituitary surgery. They guided us in identification of sella, dural layers, tumor margins and surrounding neurovascular structures. In subsequent surgeries the neurosurgeons remain standby for any help that we require for intracranial manipulations.

The limitations of our study: It is a retrospective analysis and modest sample size. But our learning curve translates positively into better and safer surgeries, greatly reducing the complications and morbidity in pituitary surgery.

Conclusion

Endoscopic endonasal transsphenoidal approach for pituitary tumor is a minimally invasive keyhole surgical technique. Aim of this technique is maximum effective surgery with minimal surgical trauma to nase- sphenoidal- sellar complex. IGNS supplements endoscopic visualization with localization of target lesion by real time stereotactic feedback using preset preoperative imaging data, thus increasing accuracy, safety and effectiveness of minimally invasive surgery. Image guided endoscopic techniques reduce postoperative discomfort, morbidity and mortality, hospital stay and overall cost. There are certain limitations set by tumor biology, tumor extension and accurate localization by target registration in IGNS for gross total tumor resections and that is why IGNS is not a replacement of surgeons experience and knowledge of regional surgical anatomy.

Declarations

Ethics approval and consent to participate

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institution and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approval from the Institute Ethics committee was obtained.

Competing interests

The Authors disclose that there is no conflict of interest. No Funding was obtained for conducting the study. The data that support the findings of this study are available on request from the corresponding author.