1. Consultant Neurosurgeon, Department of Neurosurgery, Lahore General Hospital, Lahore, Pakistan

* Correspondence: psbikramaditya@gmail.com

Keywords: endoscopic, microscopic, transsphenoidal, pituitary, adenoma, visual field, LGH

1. INTRODUCTION

The incidence of pituitary tumors is found in 10 to 15% among all intracranial tumors. Incidental pituitary tumors are found in approximately 10% of autopsies [1]. Pituitary adenoma occurs in anterior lobe of pituitary gland. Pituitary tumors are classified based on size and hormonal activity. Pituitary adenomas with size less than 10mm and ≥10mm are microadenomas and macroadenomas respectively. While hormonally active and inactive adenomas are known as functional and non-functional type respectively. The estimated prevalence rate of pituitary adenomas is around 17%. [2]. Improvement in different treatment modalities e.g. medical, surgical as well as hormonal replacement therapies have led to better outcome with low mortality rate [3]. However, maximum appropriate delivery of services, distribution of resources and latest advanced diagnostic technologies according to impact of these tumors in the community are needed for their early diagnosis and management. Surgery is commonly used in the management of pituitary adenomas [4]. Different complications such as irreversible visual impairment, ophthalmoplegia and other neurological complications of macroadenomas  are associated with morbidity; and pituitary apoplexy is the life threatening complication [5]. In 1887s, Horsle was the first who reported the open craniotomy through which pituitary tumor surgeries were performed.  While in 1907, [6] described pituitary adenoma surgery through transsphenoidal approach. In 1910, [7] brought the sublabial transseptal transsphenoidal approach into the practice and avoided using external incision and this was associated with least morbidity and mortality. In 1960s, Hardy used surgical microscope and intraoperative radiological visualization; and popularized Cushing’s technique. This microscope has advantages of stereoscopic view. in 1992, Jankowski used fully endoscopic endonasal approach for removal of pituitary lesion. This endoscopic approach has advantages of having panoramic view inside sphenoid sinus and pituitary fossa i.e.  Sella turcica, better visualization and less invasiveness which gives direct access to innermost skull base lesion. However, the endoscope has the disadvantage of lacking the stereoscopic view, which makes both endoscopic and microscopic transsphenoidal approaches equivocal in pituitary adenoma operation [8]. The trans-sphenoidal approach has been proposed as a minimally invasive surgical technique for the removal of pituitary tumors [9]. Microscopic trans-sphenoidal approach for pituitary tumors surgery remains the benchmark for future surgical techniques. In recent year, endoscopic endonasal approach is more preferred than microscopic approach. Endoscopic endonasal approach gives favourable outcome as compared to microscopic approach in terms of extent of tumors resection and control of functional pituitary tumors [10]. Cushing’s disease can be safely and effectively treated via endoscopic transsphenoidal approach. But recurrence rates remain comparable in both endoscopic and microscopic transsphenoidal approaches [11]. Resection of pituitary adenoma via endoscopic transsphenoidal approach has become more popular but is associated with higher rate of vascular injury in comparison to microscopic transsphenoidal pituitary adenoma surgery. Microscopic transsphenoidal resection of pituitary adenoma is widely and well-established approach with favourable outcome [12]. In a randomized trial, it was observed that the endoscopic and microscopic approach had   GTR 81.7% versus 62.2%, (P < 0.05) respectively. However, the incidence of CSF rhinorrhea between endoscopic and microscopic groups (P > 0.05) are similar. Endoscopic approach has advantages of wide operative field and makes easier to differentiate the tumor tissues from normal tissues and surrounding structures by giving broad lateral vision even in the corner of the Sella turcica.   According to above study, Pituitary adenoma surgery via endoscopic approach is safe and has better short-term outcome as compared to microscopic approach [13].  Another trial conducted on 25 patients in microscopic group   and 25 patients in endoscopic group for resection. In the microscopically treated group, there were 24% CSF leaks and 77% patients had gross total resection on postoperative imaging. In endoscopically treated group, 28% had CSF leaks and 66% patients had gross total resection. There was insignificant difference in both groups and authors concluded that endoscopic procedure has almost similar outcome as with microscopic procedure [14]. One trial showed that with microscopically treated cohort, there were complete resection in 60% patients, subtotal in 36% cases and 4% patients had partial resection. In endoscopically treated group, there were complete resection in 73.17% patients, subtotal in 23.17% cases and 3.65% patients had partial resection. There was insignificant difference in both groups (P>0.05) [15]. Regarding visual improvement, it was stated that the difference in the rates of visual improvement in both i.e. endoscopic approach and microscopic approach is not significant. (P > 0.05). So, rationale of this research is to compare the outcome of endoscopic and microscopic transsphenoidal pituitary adenoma surgery in terms of extent of resection, visual field improvement and CSF leakage. In literature, it has been reported that endoscopic approach is more successful and effective in removing pituitary adenoma as compared to microscopic approach. Although microscopic approach is still in use. Because of unavailability of local evidence on this regard, this study is being performed whether endoscopic or microscopic approach is better for local population. This helped to improve our practice as well as if proved through this study that endoscopic approach is better, then in future we will try to implement the use of endoscopic approach instead of microscopic approach transsphenoidal pituitary adenoma surgery.

2. MATERIALS & METHOD

The study utilized a Randomized Controlled Trial method and done at Department of Neurosurgery, Lahore General Hospital, Lahore for a period of 12 months after submission of synopsis. Sample size of 94 cases; 47 cases in each group is calculated with 80% power of test, 10% level of significance and taking expected percentage of gross tumor removal i.e. 81.7% with endoscopic approach and 62.2% with microscopic approach by using following formula: [16]

Were,

Z_1-α = 90% confidence interval (as α=10%) = 1.65

Z_1-β = 80% power of test = 1.282

P₁ = proportion of sample 1 = 0.817

P₂ = proportion of sample 2 = 0.622

P(bar) = difference in both proportions = 0.195

But Sample size of 60 cases; 30 cases in each group were taken because of limited duration of study, availability of cases and surgeries in a year. Non-Probability, Consecutive sampling technique was used. 60 patients fulfilling inclusion criteria were enrolled from wards of department of Neurosurgery, Lahore General Hospital, Lahore. Informed consents were obtained. Demographic variables (name, age, gender and duration of symptoms of pituitary adenoma) were noted. Proper history and neurological examination were carried out. Routine blood investigations were done. Then patients were randomly divided in two groups by using lottery method. In group A, patients underwent transsphenoidal pituitary adenoma surgery through endoscopic approach while in group B, patients underwent transsphenoidal pituitary adenoma surgery through microscopic approach. During and/or after surgery CSF leakage was noted. Post-operatively, patients were shifted in ICU or post-operative ward and then ward. Patients were followed-up in OPD (outpatient department) till 6 weeks of procedure and visual fields were assessed by confrontation method and were noted. Extent of resection was noted.  A predesigned proforma was used to collect information (attached). The collected data were entered and analyzed by using SPSS version 21. The study results were analyzed in an intention to treat population, as all patients had to follow the study protocol at time of randomization. Quantitative variables like age, duration of symptoms of pituitary adenoma were presented as mean and SD. Qualitative variables like gender, gross total resection, subtotal resection, partial resection, CSF leak and visual field improvement were presented as frequency and percentage. Chi-square was applied to compare frequency of gross total resection, subtotal resection, partial resection, CSF leak and visual field improvement in both groups. P-value≤0.05 was taken as significant. Data was stratified for age, gender and duration of symptoms of pituitary adenoma.

3. RESULTS & DISCUSSION

Mean age of patients in Group-A & in Group-B were 38.63±14.16 and 42.40±10.16 years respectively.  In Group-A 19(63.3%) patients were male and 11(36.7%) were female. While in Group-B 18(60%) patients were male and 12(40%) were female respectively. Mean duration of symptoms for patients in Group-A and in Group-B were 20.47±31.55 months and 14.22±19.49 months respectively. At baseline visual field, visual impairment was in 23 patients in Group-A while in 25 patients in Group-B. Table 04 Improvement in visual field was higher in Group-B patients as compared to Group-A patients. i.e. Group-A: 95.7% vs. Group-B: 96.0%, although it is insignificant (p-value>0.05). In Group-A, patients’ gross total resection was done in 22(73.3%) patients and subtotal resection was done in 8(26.7%) patients while in Group-B, gross total resection was done in 20(66.7%) patients and subtotal resection was done in 10(33.3%) patients. Partial resection was not seen in any case in either group. The difference in extent of resection in each group was insignificant (p>0.05). In Group-A, 4(13.3%) patients and in Group-B 5(16.7%) patients had CSF leak. In both treatment groups no significant difference was seen for CSF leak (p-value>0.05). Visual field improvements in both treatment groups were compared through stratification of age, gender and duration of pituitary adenoma to see the effect of these variables in both treatment groups. Effects of age, gender and duration of pituitary adenoma on resection in both treatment groups are given in Table 11, 12 & 13. Except age, gender and duration of pituitary adenoma, there was no significant impact on CSF leak in both treatment groups. Details can be seen in Table 14, 15 & 16

Table 01: Age of patients in treatment groups

	Group-A	Group-B
n	30	30
Mean	38.63	42.40
SD	14.16	10.16
Min	20	20
Max	65	65

 

Table 02: Gender of patients in treatment groups

	Group-A	Group-B	Total
Male	19(63.3%)	18(60%)	37
Female	11(36.7%)	12(40%)	23
Total	30	30	60

 

Table 03: Descriptive statistics for duration of symptoms (months)

	Group-A	Group-B
n	30	30
Mean	20.47	14.22
SD	31.55	19.49
Min	1	1
Max	96	75

 

 

Table 04: Baseline visual field

	Group-A		Group-B		Total
Normal vision	7		5		12
Visual impairment	23		25		48
Total	30		30		60
Visual impairment ↓
Bi temporal hemianopia	13		9		22
Left blind /Right light perception	1		0		1
Left blind /Right temporal hemianopia	1		0		1
Left hand movement perception/Right temporal hemianopia	6		6		12
Left temporal hemianopia/ Right normal	0		2		2
Left normal/Right hand movement perception	1		1		2
Right hand movement perception/Left temporal hemianopia	0		4		4
Left normal/ Right temporal hemianopia/	1		1		2
Right temporal hemianopia / Left light perception	0		2		2
Total		23		25		48

 

Table 05: Improvement in visual field at 6 weeks

Visual Field	Group-A	Group-B	Total
Yes	22(95.7%)	24(96.0%)	46
No	1(4.3%)	1(4.0%)	2
Total	23	25	48

 

Group-A: Endoscopic approach

Group-B: Microscopic approach

Chi-Square Test= 0.004

p-value= 0.952 (Insignificant)

Table 06: Resection in treatment groups

	Group-A	Group-B	Total
GTR	22(73.3%)	20(66.7%)	42
SR	8(26.7%)	10(33.3%)	18
PR	0	0	0
Total	30	30	60

 

Group-A: Endoscopic approach

Group-B: Microscopic approach

Chi-Square Test= 0.317

p-value= 0.573 (Insignificant)

 

Table 07: CSF Leak in treatment groups

	Group-A	Group-B	Total
Yes	4(13.3%)	5(16.7%)	9 (15.0%)
No	26(86.7%)	25(83.3%)	51 (85.0%)
Total	30	30	60

 

Chi-Square Test= 0.131

p-value= 0.718 (Insignificant)

Table 08: Visual field improvement in treatment groups stratified for Age

	20-35 Years		36-50 Years		51-65 Years
	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B
Yes	14(100%)	4(100%)	5(83.3%)	20(95.2%)	3(100%)	0(0%)
No	0(0%)	0(0%)	1(16.7%)	1(4.8%)	0(0%)	0(0%)
p-value	–		0.326		NA

 

Table 09: Visual field improvement in treatment groups stratified for Gender

	Male		Female
	Group-A	Group-B	Group-A	Group-B
Yes	16(94.1%)	14(93.3%)	6(100%)	10(100%)
No	1(5.9%)	1(6.7%)	0(0%)	0(0%)
p-value	0.927		–

 

Table 10: Visual field improvement in treatment groups stratified for Duration of pituitary adenoma

	1-20 months		21-40 months		41-60 months		>60 months
	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B
Yes	15(93.8%)	18(94.7%)	1(100%)	3(100%)	1(100%)	2(100%)	5(100%)	1(100%)
No	1(6.3%)	1(5.3%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
p-value	0.900		–		–		–

 

Table 11: Tumor resection in treatment groups stratified for Age

	20-35 Years		36-50 Years		51-65 Years
Resection	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B
GTR	15(88.2%)	5(100%)	4(50%)	15(62.5%)	3(60%)	0(0%)
STR	2(11.8%)	0(0%)	4(50%)	9(37.5%)	2(40%)	1(100%)
PR	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)	0(0%)
p-value	0.421		0.533		0.273

 

Table 12: Tumor resection in treatment groups stratified for Gender

	Male		Female
Resection	Group-A	Group-B	Group-A	Group-B
Gross Total	14(73.7%)	10(55.6%)	8(72.7%)	10(83.3%)
Subtotal	5(26.3%)	8(44.4%)	3(27.3%)	2(16.7%)
PR	0(%)	0(%)	0(%)	0(%)
p-value	0.248		0.538

 

Table 13: Tumor resection in treatment groups stratified for Duration of pituitary adenoma

	1-20 months		21-40 months		41-60 months		>60 months
	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B
GTR	18(81.8%)	17(73.9%)	0(0.0%)	1(33.3%)	1(100%)	2(66.7%)	3(50%)	0(0.0%)
STR	4(18.2%)	6(26.1%)	1(100%)	2(66.7%)	0(0.0%)	1(33.3%)	3(50%)	1(100%)
PR	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)	0(0.0%)
p-value	0. 524		0.505		0.505		0.350

 

Table 14: CSF leakage in treatment groups stratified for Age

	20-35 Years		36-50 Years		51-65 Years
	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B
Yes	2(11.8%)	0 (0.0%)	1(12.5%)	5(20.8%)	1(20.0%)	0(0.0%)
No	15(88.2%)	5 (100%)	7(87.5%)	19(79.2%)	4(80.0)	1(100%)
p-value	0.421		0.601		0.624

 

Table 15: CSF leakage in treatment groups stratified for Gender

	Male		Female
	Group-A	Group-B	Group-A	Group-B
Yes	3(15.8%)	2(11.1%)	1(9.1%)	3(25%)
No	16(84.2%)	16(88.9%)	10(90.9%)	9(75.0%)
p-value	0.677		0.315

 

Table 16: CSF leakage in treatment groups stratified for Duration of pituitary adenoma

	1-20		21-40		41-60		>60
	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B	Group-A	Group-B
Yes	1(4.5%)	4(17.4%)	1(100%)	1(33.3%)	0(0.0%)	0(0.0%)	2(33.3%)	0(0.0%)
No	21(95.5%)	19(82.6%)	0(0.0%)	2(66.7%)	1(100%)	3(100%)	4(66.7%)	1(100%)
p-value	0.170		0.248		NA		0.495

 

Endoscopy expands the limits of the surgeons’ performance of transsphenoidal surgery by improving visualization that they could not have accessed before. The characteristic of minimal invasiveness explains the positive outcomes and decreases post-operative complications rate via endoscopic approach in comparison with the microscopic one. Results of this study showed that visual field improvement was nearly equal in both approaches i.e. Group-A: 95.7% vs. Group-B: 96%, but the difference is insignificant (p-value>0.05). Studies have shown no significant difference regarding visual improvement for both treatment modalities. Mahmoud Messerer in his study showed improved visual outcome as 51% with endoscopic approach and 50% with microscopic approach [17]. An author [18] in his study reported the recovery of visual function as 91.7% with Endoscopic endonasal transsphenoidal surgery.  A study reported improved visual function in patients as 86% who underwent endoscopic endonasal trans-sphenoidal surgery of pituitary macroadenomas [19]. however, in our study the difference in the rate of improvement in visual field with endoscopic and microscopic approaches are insignificant and is in line with the above-mentioned studies. Regarding CSF leak, no significant difference was seen in both groups i.e. Group-A: 13.3% vs. Group-B: 16.7% (p-value=0.131). Similar findings were reported by [14], M (Endoscopic-Op: 12.1% vs. Microscopic Op: 8.5%, p-value=0.33), Hanuman Prasad Prajapati (Endoscopic-Op: 15.38% vs. Microscopic Op: 11.76%, p-value=0.937), a recent meta-analysis reported the similar findings regarding no significant difference for CSF leak for both treatment modalities [20-22]. In this study, gross total resection was done in 73.3% and subtotal resection in 26.7% patients who were operated with endoscopic approach while patients who were operated with microscopic approach, among them gross resection was achieved in 66.7% and subtotal resection in 33.3% patients. Although with endoscopic approach, gross resection rate was higher but still it is not statistically significant (p>0.05). A study showed that with microscopically treated cohort, the complete, subtotal and partial resection were achieved in 60%, 36%, 4% patients respectively. While in endoscopically treated group, complete resection was achieved in 73.17% patients, subtotal in 23.17% cases and 3.65% patients had partial resection. There was insignificant difference in both groups (P>0.05) [23]. Different author showed higher rate of tumor resection in patients who underwent endoscopic approach as compared to microscopic approach. Result of this study regarding resection of tumor is in line with the results reported by above mentioned authors [24-26]. An author concluded that quality of resection is significantly improved after one year in those who were operated via endoscopic approach (GTR: 74% vs 50%, p=0.002) [27]. A study showed that trans-sphenoidal surgery with endoscope has better results in both tumor resection and control of disease in comparison with microscopic approach [28]. An author showed that the rate of control of disease is better when resection was done via endoscopic approach in comparison to the microscopic approach [29].  A study showed that endoscopic approach is better than the microscopic surgery in macroadenomas and adenomas with extension above the Sella because it helps to gain access and control over the para Sellar extension of the tumor. In addition, a previous pituitary or sinus surgery and the flap that might affect the intervention should be stratified in future studies [30]. Pituitary surgery via endoscopic trans-sphenoidal approach is a growing technique and comparison between microscopic and endoscopic surgery should be performed to evaluate merits and demerits. Operating microscope does not visualize whole of the sphenoid sinus, Sella turcica and surrounding structures. The endoscopic approach had a widened operative field of view, eliminates the need of a nasal speculum as guide and makes easier to differentiate of tumor tissues from gland. Endoscopic surgery had minimal damage to nasal cavity, minimize postoperative morbidity and with angled endoscope all area of nose and para-nasal sinus can be completely visualized. Optical properties of endoscope are better than the operating microscope. Endoscope gives an exquisite view of optic bulge, carotid bulge and optic carotid recess which reduces the chances of disastrous injury to internal carotid artery [31]. In our study, the mean duration of symptoms for patients in Group-A and in Group-B were 20.47±31.55 months and 14.22±19.49 months respectively. It was observed that around 75% cases presented within 12months of symptoms, while remaining 25% patients presented in 3-8 years (36-96months) of appearance of symptoms. Thus, there was presence of extreme values in data, so we got larger standard deviation than mean. This may be because patients of prolactinoma intolerance to medication and nonfunctional adenomas presented within 1-12 months of symptoms while patients of other types of pituitary adenomas presented between 36-96 months of symptoms. There are several limitations of endoscopic approaches as it requires a bloodless surgical field and has a steep learning curve. In endo-nasal endoscopic surgery, there is no need of sublabial or nasal incision and elevation of mucoperichondrial flap from nasal septum. Hence, the possible complications of septal and para nasal sinus areas are eliminated.

4. CONCLUSIONS

Visual field improvement was slightly higher in patients who were operated on via microscopic approach as compared to those with endoscopic approach but the difference in both the groups is insignificant i.e. Group-A: 95.7% vs. Group-B: 96% (p-value>0.05). Regarding CSF leak, the difference was observed to be insignificant in both treatment groups i.e. Group-A: 13.3% vs. Group-B: 16.7% (p-value>0.05). Gross total resection (GTR) was seen in 73.3% and subtotal resection (STR) in 26.7% patients who were operated on with endoscopic approach while patients who were operated with microscopic approach, GTR was in 66.7% and STR in 33.3% patients (p>0.05) which is insignificant. Both treatment modalities are nearly equally effective in treating pituitary adenoma. Although with endoscopic approach comes up with higher gross total resection of pituitary adenoma. Results of this study showed that both treatment modalities are nearly equally effective in treating patients presenting with pituitary adenoma. Both the modalities have their own advantages and pitfalls. Although with endoscopic approach comes up with higher gross total resection of the tumor.  But in case of visual field improvement and CSF leakage, there is no significant difference in outcome of both treatment modalities. So further large scale randomized controlled studies are need to clarify the controversy regarding the effective and preferred technique for treating transsphenoidal pituitary adenoma.

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