Endoscopic versus Microscopic Pituitary Adenoma Surgery: A Single-center Study
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.266241
Source of Support: None, Conflict of Interest: None
Keywords: Endoscopic, microscopic, pituitary adenoma, transnasal approach
The approach to the sellar region pathology has been evolving throughout the years, since Horsley in 1889, who first performed a transcranial resection of a pituitary adenoma, to the introduction of the microscope in the 1950s by Hardy and Wilgser, who performed the sublabial transsphenoidal approach described by Cushing.,,, The endoscopic transnasal approach was used in the early 1990s by Jankowski et al., later perfected by Cappabianca et al., Carrau et al., and Jho.,,, Transsphenoidal surgery became the gold standard in the surgical treatment of pituitary adenomas, but the comparative efficacy of microscopic and endoscopic transsphenoidal surgery has not been fully studied despite the adoption of endoscopic surgery in many centers, including ours. The objective of this study is to compare both techniques used to treat pituitary adenomas with the aim to objectify their differences concerning results and complication rates.
A retrospective analysis was conducted, comparing adult patients with pituitary adenomas who had undergone transnasal microscopic surgery between January 2006 and December 2014 with the patients who had been operated on with endoscopic surgery between March 2011 and December 2014 at Hospital Italiano de Buenos Aires. Two neurosurgeons performed the surgeries. One junior surgeon practices fully endoscopic transsphenoidal approach exclusively and one senior surgeon practices microsurgery exclusively, using a nasal speculum. The Hospital's electronic medical records were used for data collection. The approval of the ethics committee of our institution was obtained prior to performed the study and all the data was treated with maximum confidentiality, in accordance with legal regulations in our country. We included those patients with pre- and postoperative clinical, hormonal, and opththalmological studies, as well as with intravenous contrast-enhanced magnetic resonance imaging (MRI) scans of the sellar region. All patients were followed up for at least 1 year and evaluated at 3, 6, and 12 months post surgery. The cases followed up in other institutions lacking complete medical records were excluded. Epidemiological data (age and sex) and percentage of pathologies treated were analyzed. According to the imaging studies, we studied size, extension, and degree of tumor invasion, and results of the resection and decompression of the optic chiasm. With postoperative laboratory studies and campimetry, hormonal control of the disorder and visual field results were objectified. Furthermore, we analyzed number of reoperated patients, number of patients who received medical treatment or radiotherapy, length of stay, and surgical duration. Postoperative complications were divided into medical and neurosurgical. The first group included diabetes insipidus and hormone deficiency derived from adenohypophysis or panhypopituitarism. Neurosurgical complications were subdivided into rhinosinusal, cerebrospinal fluid (CSF) fistula, meningitis, and bleeding in the surgical site.
Preoperative hormonal profile was analyzed, which included doses of growth hormone (GH) and insulin-like growth factor (IGF 1), prolactin, adrenocorticotropin, serum cortisol, salivary cortisol, urinary free cortisol, thyrotropin, free thyroxine, luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol. Standardized postoperative hormonal controls were performed at 3, 6, and 12 months in patients with functioning adenomas and, according to the case, in patients with nonfunctioning adenomas. In selected cases, axis suppression hormone tests or cavernous sinus catheterization was performed for the diagnosis of Cushing's disease or acromegaly. Remission was evaluated during the first postoperative consultation 3 months after surgery. It was considered when normal postoperative biochemical values of IGF 1 were obtained according to age and sex, a GH suppression test below 1 ng/mL and morning plasma cortisol values below 1–2 μg/dL, respectively. Then the postoperative medical controls were focused to detect hormone deficits and therefore the need for hormone replacement therapy.
We analyzed MRI scans with and without gadolinium enhancement with protocol of the sellar region (coronal T1-weighted thin-slice sequence without gadolinium enhancement, gadolinium-enhanced T1- and T2-weighted sequence, and gadolinium-enhanced sagittal T1-weighted thin-slice sequence) both preoperatively and 3 months after surgery. Tumor pathology and invasion of adjacent structures (cavernous sinuses and suprasellar cistern) were assessed, as well as the anatomy of the nostrils and existence of septae in the sphenoid sinus. According to size, lesions were classified into macroadenomas (>1 cm) and microadenomas (<1 cm). The classifications by Hardy et al., modified by Wilson and Knosp et al., were used to categorize tumor extension and degree of cavernous sinus invasion, respectively., Following the publications by Cappabianca et al., three degrees of postoperative resection were defined: total resection (when no remaining tumor is observed on MRI scans 3 months after surgery), subtotal resection (more than 80% of tumor resection compared with preoperative imaging), and partial resection (less than 80%).
Computerized visual field testing was performed, preoperatively and 3 months after the intervention, on those patients who came to consultation for visual disturbances and/or on those whose imaging studies showed optic chiasm compression. Visual acuity and campimetric deficits were evaluated.
Bivariate analysis of the quantitative categorical variables was performed with Fisher's exact test, since they were dichotomous variables. A P < 0.05 was considered statistically significant. The statistical analysis was performed with SPSS Statistics 17.0.
A total of 259 patients underwent microsurgery and 140 patients endoscopy. In the first group, 150 patients were female (58%) and 109 patients male (42%), and the second group involved 79 women (56%) and 61 men (44%). The average age in years was similar in both groups, 51 years in the first group (17–90 years) and 48.5 years (18–85 years) in the second group. As regards pathologies treated, the first group presented with 99 cases of nonfunctioning adenomas (38.2%), 66 cases of Cushing's disease (25.5%), 73 cases of acromegaly (28.2%), 18 cases of prolactinoma (7%), and 3 cases of gonadotrophinoma (1.1%). The second group, treated endoscopically, involved 59 nonfunctioning adenomas (42.1%), 41 patients with acromegaly (29.3%), 33 patients with Cushing's disease (23.6%), 6 patients with prolactinoma (4.3%), and 1 patient with gonadotropinoma (0.7%). In both groups, pathology reported several positive markers for hormone production in a high number of patients. These were categorized according to each patient's clinical manifestations.
In the cases of patients who underwent microscopy, 65.2% presented with macroadenomas (n = 169), of whom 35.5% showed cavernous sinus invasion (n = 60) and 34.9% presented with suprasellar cistern invasion obliterating the anterior recess of the third ventricle (n = 59). Comparatively, in the group of patients who underwent transnasal endoscopy, 78.6% harbored macroadenomas (n = 110), of whom 56.4% (n = 62) presented with cavernous sinus invasion and 36.4% presented with suprasellar cistern invasion obliterating the anterior recess of the third ventricle (n = 40) [Table 1].
The average surgical time was 1.4 h for the first group of patients, versus 1.8 h in the cases of patients who underwent endoscopy. The average length of stay was 4.5 days versus 3 days for patients not requiring a closed unit.
Of the patients who underwent microscopic surgery, postoperative MRI showed, at 3 months, total tumor resection in 70.6% of cases (n = 183), 25.1% achieved subtotal resection greater than 80% (n = 65), and 4.3% showed partial resection less than 80% (n = 11). Of the patients with macroadenomas, as mentioned above (n = 169), 60 had invasion of the cavernous sinus (35.5%); complete resection was achieved in 21 cases, belonging to grades I and II of the classification by Knosp et al. (35%). Of the patients with macroadenomas, 28 cases (16.6%) presented with suprasellar cistern invasion obliterating the anterior recess, or deformation of the floor of the third ventricle (grades B and C of the classification by Hardy et al., modified by Wilson  without invasion of the cavernous sinus), of which complete resection was achieved in 15 cases (53.6%). On the other hand, of the patients who underwent transnasal endoscopy, complete resection was achieved in 60% of the cases (n = 84), subtotal resection greater than 80% in 32.1% of cases (n = 45), and partial resection less than 80% in 7.9% of cases (n = 11). Of the 62 patients with pituitary macroadenomas with invasion of the cavernous sinus (56.4%), complete resection was achieved in 29 cases, belonging to grades I and II of the classification by Knosp et al. (46.8%). Eleven patients (10%) harbored macroadenomas grades B or C of the classification by Hardy et al., modified by Wilson, without invasion of the cavernous sinus; in 5 of these cases, complete resection was achieved (45.5%) [Table 2] and [Table 3].
Of the patients with subtotal or partial resection, or of those who relapsed, operated on with microscopic surgery (n = 76), 33 cases were reoperated (43.4%). On the other hand, of the patients who had undergone endoscopy with subtotal or partial resection, or who had relapsed (n = 57), only 4 (7%) of them were reoperated on. Regarding the percentage of patients who received radiotherapy or pharmacological treatment with somatostatin analogs, dopaminergic agents, or others following specialized prescription, there were no significant differences between both groups of patients.
To analyze disease control in patients with functioning pathology, clinical improvement and endocrinologic lab parameters were assessed at 3, 6, and 12 months after surgery. In the group of patients who had undergone microscopy (n = 160), active disease persisted in 34 patients (21.3%) despite surgical treatment; 11 of them were microadenomas and 23 macroadenomas, 14 were cases of acromegaly (8.8%), 5 prolactinomas (3.1%), and 15 Cushing's disease (9.3%). Regarding those patients who had undergone transnasal endoscopy (81 cases), active disease persisted in 20 patients despite surgical treatment (24.7%); 5 of these cases were microadenomas and 15 macroadenomas. As regards distribution of pathology, results were as follows: 10 cases of acromegaly (12.3%), 2 prolactinomas (2.5%), and 8 cases of Cushing's disease (9.9%) [Table 4].
Regarding the tumor samples sent to pathology, in addition to markers for hormone production, MIB 1 proliferation index was analyzed: 2.3% on average in the case of patients operated on with microscopy, and slightly higher in those patients who had undergone endoscopy (2.8%).
Postoperative computerized visual field testing
From the group of patients who underwent microscopy, 91 (35%) presented with visual field defects, in all cases macroadenomas. After surgery, 55% (n = 50) showed improvement, 17.6% (n = 16) recovered, 23% (n = 21) reported no changes, and 4.4% (n = 4) deteriorated. Of the patients who had undergone endoscopy, computerized testing showed visual field defects in 61 of them (44%), of whom 50.8% showed improvement 3 months after surgery (n = 31), 23% patients recovered (n = 14), 23% (n = 14) reported no changes, and 3.2% (n = 2) deteriorated. In both groups of patients, visual field deterioration was observed in the cases of intrasellar bleeding.
A total of 68 patients suffered complications in the group operated on with microscopy (26.3%). Medical complications involved 27 cases of diabetes insipidus (10.4%), 21 of which were transient (9 cases required desmopressin), and 6 cases were permanent. Twenty-six patients presented with some degree of anterior pituitary hormone deficiency (10%), which required hormone replacement therapy. In the cases of patients who had undergone transnasal endoscopy, 21 patients suffered complications (15%). Nine patients developed diabetes insipidus (6.4%), which was transient with spontaneous resolution in four cases, transient in two cases requiring desmopressin, and permanent in three cases. Some degree of anterior pituitary hormone deficiency was observed in 17 patients (12%), who required hormone replacement therapy.
Regarding surgical complications, rhinosinus complications were uncommon in both patient groups. One case (0.4%) of chronic sinusitis was reported requiring drainage and prolonged antibiotic therapy in the group operated on with microscopy, and one case of anterior epistaxis in the group of patients who had undergone endoscopy (0.7%).
Eight cases of postoperative CSF fistula were reported in the patients who had undergone microscopy (3.1%), two of whom required a new transnasal procedure for closure (0.8%). The remaining patients were treated conservatively with evacuating lumbar puncture. In the second group, three (2.1%) cases of CSF fistula were reported, all of them effectively treated with evacuating lumbar punctures. No lumbar drain was placed in either group. Seven cases of postsurgical meningitis (2.7%) were reported in the first group of patients, only one of which showed evident fistula, whereas three (2.1%) cases were reported in the second group, one of them with evident fistula. Both cases were effectively treated with antibiotics during 14 days with no associated complications reported.
Of the patients who had undergone microscopy, four (1.5%) cases of bleeding in the surgical site were reported, three of them requiring a new transnasal surgery for evacuation; all these patients had nonfunctioning adenomas. Three (1.2%) deaths were reported; two of them due to respiratory infections associated with mechanical ventilation and sepsis and one of them because of intracranial hypertension with brain stem injury. Two patients who had undergone endoscopy developed a postoperative intrasellar hematoma. Both of them required endoscopic transnasal surgery for evacuation (1.4%). Only one (0.7%) death was reported due to sepsis for ventilator-associated pneumonia [Table 5].
Regarding percentages of complete resection, after analyzing the data obtained with both methods, we found a statistically significant difference favoring the microscopic technique, of approximately 10% (P = 0.034431). Comparative analysis was later performed of those patients without and with cavernous sinus invasion, most of them belonging to the endoscopy group. No statistically significant differences were found regarding the percentage of complete resection in the group of patients without cavernous sinus invasion (P = 0.202371). There were no statistically significant differences in the patients with cavernous sinus invasion, but there was in fact a slight tendency favoring the endoscopic technique (P = 0.052976). Those patients presenting with suprasellar invasion without cavernous sinus invasion did not show higher benefit with either technique (P = 0.731094).
As regards hormonal control, there were no statistically significant differences in the number of patients with active disease or in remission (P = 0.62402). If only those patients with cavernous sinus invasion are analyzed, no significant differences are observed between the groups, although there is a slight tendency favoring the endoscopic technique (P = 0.10178). This statistical result might be due to the small sample number; that is to say, there are few patients with functioning adenomas and cavernous sinus invasion.
Regarding improvement or normalization of computerized visual field testing, they were compared with those patients who showed no changes or those who deteriorated. No significant differences were found in the groups studied (P = 1).
When the number of total complications between both surgical techniques is analyzed, a statistically significant difference is observed: 16% more complications using the microsurgical technique (P = 0.011501). When each complication was analyzed particularly, no differences were found between them, probably due to the small sample number (diabetes insipidus: P =0.204576, panhypopituitarism: P = 0.504606, rhinosinusal: P = 1, CSF fistula: P = 0.753658, meningitis: P = 1, death: P = 1).
Transnasal transsphenoidal surgery, whether we use the microscope or the endoscope, has become, throughout the years, the treatment of choice for the pathology of the sellar region, since it is a minimally invasive procedure that uses the body's own pneumatic cavities to reach a small space with highly relevant anatomical elements. Despite the extensive literature comparing the techniques, and agreeing that both are safe and efficient, no consensus has yet been reached on which is the best as regards postoperative results, hormonal control, visual field improvement, and complication rates. In fact, the available publications are limited by short follow-up periods, small sample numbers, and nonrandomized studies. Thus, the choice of either technique is, to date, valid for the treatment of pituitary adenomas.
Concerning the percentage of tumor resection on weighted postoperative MRI and as described above, at first we encountered a higher number of patients with complete tumor resection after microscopic surgery (70.6% vs. 60%); however, as previously reported, the populations analyzed in both groups were not homogeneous, since a higher number of patients with cavernous sinus invasion underwent endoscopy (36.4% vs. 56.9%). On the other hand, the percentage of complete resection via endoscopy is similar to that of other publications, such as the study by Cappabianca et al. When the patients with invasive macroadenomas were analyzed, we found that in the group treated endoscopically the percentage of patients with complete tumor resection was higher than that of those who had undergone microscopy (35% vs. 46.8%). This might be explained by the fact that the endoscope is a tool that can be introduced into the sella turcica to explore the lateral spaces in search of tumor remnants. In the cases of patients with cavernous sinus invasion and complete resection, all of them belonged to grades I and II of the classification by Knosp et al. Therefore, we conclude that there may not actually exist a cavernous sinus invasion in some cases, and that it may only be objectivized during surgery by means of the endoscope., On the other hand, as regards resection percentages for those patients with suprasellar cistern invasion grades B and C of the classification by Hardy et al., modified by Wilson, without cavernous sinus invasion, the percentage of patients with complete resection was higher in those patients who had undergone microscopy (53.6% vs. 45.5%); however, this difference was not statistically significant. The use of 30° and 60° optical fibers is likely to improve these results. To that end, a learning curve on surgical anatomy identification is required, to avoid injuring neighboring structures such as the adenohypophysis, the suprasellar cistern, and vascular elements. Regarding the information available in the literature, the studies by Duz et al. (2008), Higgins et al., (2008) and Neal et al. (2008) report better results with the endoscopic approach, whereas O'Malley et al. (2008) and Casler et al. (2005), among others, show higher percentages of resection with the microscopic technique.,,,, These studies do not distinguish between those patients with or without cavernous sinus invasion, and the numbers of patients included in the studies are small; therefore, no conclusive results can be established. Concerning pathological anatomy, even though further studies are warranted, we believe that a high tumor proliferation marker (Ki-67) might be a factor associated with presence of persistent disease and higher tumor recurrence rates, regardless of the technique applied.
Three published studies compare degree of remission in patients operated on for functioning adenomas. In these studies, no significant differences are observed between the procedures regarding hormonal control after surgical resection, except in the study by D'Haens et al., which proves a tendency toward better hormonal control after endoscopic resection (63% vs. 50%), and it did prove to be statistically significant in the case of patients with noninvasive macroadenomas (78% vs. 43%, P = 0.43).,, In our experience, differences in hormonal control were not significant in either group. The microscopic technique proved to be slightly superior; however, as mentioned above, the populations treated were different, with a higher number of patients with cavernous sinus invasion operated on with the endoscopic technique. Even though the degree of disease control was similar in the group of patients without macroadenomas, there were, in fact, differences in those patients with cavernous sinus invasion, whose remission rate was higher with the endoscopic technique (33.3% vs. 64%), although this difference was not statistically significant either [Table 6].
As we know, in the case of macroadenomas causing compression of the optic chiasm, the main objective of the surgery is decompression rather than complete tumor resection. Regarding visual field improvement, and like the available literature reporting this result, there were no significant differences between the groups; thus, a longer follow-up period may be needed for long-term assessment.,,, It should be considered that visual recovery is associated with how long the optic nerve has been compressed and that, in our population, consultation is usually late. Optical coherence tomography would allow us to determine which patients could and could not recover their vision.
Concerning the total number of complications, there was actually a statistically significant difference between both techniques, the endoscopic approach being the safer one. When each complication was particularly analyzed, there were no significant differences between both techniques regarding anterior pituitary hormone deficiency. This proves to be in keeping with the available literature.,,,,, As regards the development of postoperative diabetes insipidus, in our experience, the percentage of patients was lower in the cases using the endoscopic technique (6.4% vs. 10.4%); however, this difference was not significant. Only one statistically significant difference is confirmed in the study by Neal et al., which also shows a lower incidence of this complication in those patients operated on with the endoscopic technique. No differences between the two groups are observed in the rest of the literature.,,,,,
In some available studies, a higher risk is observed of CSF fistula in those patients operated on via transnasal endoscopic approach, like the work by Graham et al (2009), D'Haens et al. (2009), and O'Malley et al. (2008).,, In our experience, there was no significant difference: 3.1% for the microscopic technique and 2.1% via endoscopy. Thus, it is of utmost importance to keep the suprasellar cistern intact and, if intraoperative CSF leakage is observed, to repair the defect by reconstructing the sellar floor using a pediculated graft and fibrin glue. Neither significant differences were observed regarding development of meningitis in both groups, which is consistent with the available literature.,,
Rhinosinusal complications were uncommon in both groups, and no differences were found regarding their incidence. In the study by White et al., a lower number of rhinosinusal complications was reported from patients who had undergone endoscopy.
Regarding development of hematoma in the surgical site, no differences were observed between both patient groups: 1.5% in the case of patients who had undergone microscopy and 1.4% in those patients operated on endoscopically. The incidence of this complication in the series of patients operated on with endoscopy is similar to the results obtained by Cappabianca et al., who studied 146 patients with pituitary adenomas operated on via transnasal endoscopy, 2 of whom had sellar hematomas (1.4%), 1 requiring surgical evacuation. Since the studies comparing both procedures include a small number of patients, and because this complication has not been reported, or has not been considered at the time of analyzing both procedures, in our experience, the two techniques would be similar regarding bleeding management and control, also thanks to the development of new hemostatic materials.
Regarding the length of hospital stay, in our experience, there was a small difference in the average stay: 3 days for endoscopic surgery and 4.5 days for the microsurgical technique. These figures are similar to other series published in the literature.,,,,,,
The most important limitation we found is that our study is retrospective nonrandomized. Another fact is that the number of patients enrolled in the endoscopic group was smaller, because we started using this surgical technique in 2009. This is a comparison between two groups operated by different surgeons; experience and learning curve were not included in the analysis. Finally, for a reason we cannot explain, the endoscopic group has more patients with cavernous sinus involvement. Although we slightly consider that the endoscopic approach is maximized in giant adenomas, the difference was not statistically significant.,
Both techniques are valid for the treatment of noninvasive adenomas. However, endoscopy proves to be superior for resection of macroadenomas with invasion of the cavernous sinus regarding both hormonal control of the disease and percentage of tumor resection, showing lower risks of global postoperative complications.
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Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]