Comparison of outcomes between a less experienced surgeon using a fully endoscopic technique and a very experienced surgeon using a microscopic transsphenoidal technique for pituitary adenoma

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OBJECT

The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients.

METHODS

Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR.

RESULTS

Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm3 vs 0.20 cm3, p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different.

CONCLUSIONS

A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm3. The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.

ABBREVIATIONSCSF = cerebrospinal fluid; EOR = extent of tumor resection; GTR = gross-total resection; QOL = quality of life; STR = subtotal resection; TNTS = transnasal transsphenoidal.

OBJECT

The comparative efficacy of microscopic and fully endoscopic transsphenoidal surgery for pituitary adenomas has not been well studied despite the adoption of fully endoscopic surgery by many pituitary centers. The influence of surgeon experience has also not been examined in this setting. The authors therefore compared the extent of tumor resection (EOR) and the endocrine outcomes of 1 very experienced surgeon performing a microscopic transsphenoidal surgery technique with those of a less experienced surgeon using a fully endoscopic transsphenoidal surgery technique for resection of nonfunctioning pituitary adenomas in a concurrent series of patients.

METHODS

Post hoc analysis was conducted of a cohort of adult patients prospectively enrolled in a pituitary adenoma quality-of-life study between October 2011 and June 2014. Patients were followed up for 6 months after surgery. Patients were treated either by a less experienced surgeon (100 independent cases) who practices fully endoscopic surgery exclusively or by a very experienced surgeon (1800 independent cases) who practices microscopic surgery exclusively. Patient demographic characteristics, tumor characteristics, hypopituitarism, complications, and length of hospital stay were analyzed. Tumor volumes and EOR were determined by formal volumetric analysis involving manual segmentation of MR images performed before surgery and within 6 months after surgery. Logistic regression analysis was used to determine predictors of EOR.

RESULTS

Fifty-five patients underwent fully endoscopic transsphenoidal surgery, and 80 patients underwent fully microscopic transsphenoidal surgery. The baseline characteristics of the 2 treatment groups were well matched. EOR was similar between the endoscopic and microscopic groups, respectively, as estimated by gross-total resection rate (78.2% vs 81.3%, p = 0.67), percentage of tumor resected (99.2% vs 98.7%, p = 0.42), and volume of residual tumor (0.12 cm3 vs 0.20 cm3, p = 0.41). Multivariate modeling suggested that preoperative tumor volume was the most important predictor of EOR (p = 0.001). No difference was found in the development of anterior gland dysfunction (p > 0.14), but there was a higher incidence of permanent posterior gland dysfunction in the microscopic group (p = 0.04). Combined rates of major complications and unplanned readmissions were lower in the endoscopic group (p = 0.02), but individual complications were not significantly different.

CONCLUSIONS

A less experienced surgeon using a fully endoscopic technique was able to achieve outcomes similar to those of a very experienced surgeon using a microscopic technique in a cohort of patients with nonfunctioning tumors smaller than 60 cm3. The study raises the provocative notion that certain advantages afforded by the fully endoscopic technique may impact the learning curve in pituitary surgery for nonfunctioning adenomas.

ABBREVIATIONSCSF = cerebrospinal fluid; EOR = extent of tumor resection; GTR = gross-total resection; QOL = quality of life; STR = subtotal resection; TNTS = transnasal transsphenoidal.

The transnasal transsphenoidal (TNTS) approach was originally described in 1907 and popularized by Harvey Cushing.16 However, poor light penetration within a narrow surgical corridor frequently resulted in subtotal tumor resection and high complication rates, leading Cushing to abandon this approach in favor of a transcranial route.8 The TNTS approach was revisited when Jules Hardy introduced the operating microscope in 1962, which dramatically improved illumination and intraoperative magnification of critical neurovascular structures. Although microscopic TNTS surgery later became the gold standard in the surgical treatment of pituitary lesions, many pituitary centers soon adopted a fully endoscopic technique because of the superior visualization provided by endoscopy. Endoscopy provides a wider field of view, angled viewing to inspect the cavernous sinus and suprasellar space, and high magnification to differentiate normal gland from adenoma. Proponents of the endoscopic TNTS approach suggest that improved visualization may translate into a higher rate of pituitary function preservation and a greater extent of tumor resection (EOR) than are possible with the microscope.4,18 This transition from a microscopic to a fully endoscopic pituitary surgery technique has occurred despite limited objective comparative outcome data.6,10,21,23

In 2011, our institution initiated a prospective endonasal quality-of-life (QOL) study to compare patients’ QOL with respect to sinonasal symptoms after direct endonasal uninostril microscopic and fully endoscopic binostril TNTS approaches for sellar pathology.12 To better understand the impact of surgical technique on outcomes, we retrospectively studied this cohort of patients to determine EOR using formal volumetric techniques, endocrine outcomes, and complications. We also sought to understand these findings in the context of treatment by surgeons with differing levels of experience.

Methods

Study Design and Patient Population

A retrospective analysis was conducted of a prospective cohort of patients enrolled in a pituitary QOL study.12 This study was approved by the Institutional Review Board at St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, and registered (NCT01504399: Rhinological Outcomes in Endonasal Pituitary Surgery [clinicaltrials.gov]). The study adhered to the principles set forth in the US Code of Federal Regulations, Title 45, Part 46, Protection of Human Subjects, Revised January 15, 2009. Eligible patients were consecutive English- or Spanish-speaking adults (18 years old or older) with clinically nonfunctioning adenomas who underwent transsphenoidal tumor resection at Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona, between October 2011 and June 2014. Exclusion criteria consisted of a history of prior radiotherapy to the paranasal sinus region or skull base.

Two neurosurgeons (A.S.L. and W.L.W.) of differing levels of experience participated in the study. One junior (100 independent cases) surgeon (A.S.L.) practices fully endoscopic binostril transsphenoidal surgery exclusively, and 1 senior (1800 independent cases) surgeon (W.L.W.) practices direct uninostril microscopic surgery exclusively, using a nasal speculum without supplemental endoscopy. Patient and tumor characteristics did not influence surgical technique selection. Both surgeons attempted pseudocapsular tumor resection and gland preservation whenever possible. Patients were managed in a multidisciplinary pituitary clinic environment under the care of a pituitary endocrinologist (L.K.). A common institutional order set and postoperative care pathway were used by both surgeons.

Data Collection and Analysis

Study data, including patient demographic characteristics, surgical approach details, and endocrine end points, were collected and entered into a research database template by a research nurse. Deidentified patient data were analyzed by a biostatistician. EOR volumetric data were the only variables collected retrospectively. All other variables were collected as part of the prospective QOL study.

Extent of Resection Analysis

Preoperative MRI scans performed within 6 months of surgery and postoperative MRI scans performed within 6 months after surgery were used for analysis. Preoperative and postoperative MRI scans were performed on 1.5-T or 3-T scanners with dedicated noncontrast and postcontrast pituitary coronal sequences. EOR was determined using one of 2 methods. First, EOR was dichotomized into gross-total resection (GTR) and subtotal resection (STR) by neuroradiologists. This is the most commonly reported method in pituitary series.6,16,21 Patients with questionable residual tumor on postoperative imaging were assigned to the STR outcome. Second, formal volumetric analysis using manual tumor tracing was performed using manual segmentation with region of interest analysis to measure tumor volume (in cm3) on the basis of contrast enhancement, as previously described.5,20

Statistical Analysis

Statistical analyses were performed by a biostatistician. Frequencies and descriptive statistics included counts, percentages, means, and standard deviations. Mean differences between continuous variables were analyzed using the independent-sample t-test and the chi-square test or Fisher’s exact test to test for an association between categorical variables. Logistic regression was used to predict total resection from large tumor status, a Knosp score of 3 or 4, surgical visualization, and prior surgery. A p value of < 0.05 was considered significant. Statistical analyses were conducted with the SPSS statistics software package (SPSS Statistics for Windows, Version 21.0, IBM Corp.). A power analysis concluded that a sample size of 135, with 55 in one group and 80 in the second, allowed for 80% power to detect a medium effect as measured by Cohen’s d of 0.50 with an alpha of 0.05. This power calculation was based on the Student t-test to assess for differences between 2 independent means.

Results

A total of 137 patients underwent transsphenoidal surgery for nonfunctioning adenoma with a fully endoscopic binostril technique (n = 57) or a direct endonasal microscopic technique (n = 80) between October 2011 and June 2014. At the start of the study, the endoscopic surgeon had completed 100 independent cases and the microscopic surgeon had completed 1800 independent cases. The distribution of preoperative tumor volumes for each group is summarized in Fig. 1. Two patients in the endoscopic group who had extremely large tumor volumes (80 cm3 and 90 cm3, respectively) greater than 4 standard deviations above the mean were excluded from the analysis since they were outliers, yielding cohorts of 55 endoscopic and 80 microscopic patients to analyze. The majority of the patients in each group had tumor volumes less than 20 cm3. Baseline patient and tumor characteristics of the patients analyzed were well matched with respect to sex, tumor volume, suprasellar tumor volume, and Knosp grade (Table 1). There was a trend toward more patients in the microscopic group having undergone previous transsphenoidal surgery (p = 0.07). The mean length of hospital stay after surgery was similar between the 2 groups (endoscopic 2.3 ± 1.2 days vs microscopic 2.8 ± 3.4 days, p = 0.29), as was the number of patients undergoing a second-stage surgery for additional tumor removal (endoscopic 5.5% [n = 3] vs microscopic 7.5% [n = 6], p = 0.74). The most common indication for surgery in both groups was chiasmopathy (50.9% [n = 28] vs 56.3% [n = 45], respectively), followed by incidentally discovered (40.0% [n = 22] vs 37.5% [n = 30]) and apoplexy (10.9% [n = 6] vs 3.8% [n = 3]) (Table 1).

FIG. 1.
FIG. 1.

Histogram demonstrating the frequencies of preoperative tumor volumes for the endoscopic group (left side) (n = 57) and the microscopic group (right side) (n = 80) undergoing tumor resection for nonfunctioning pituitary adenomas. Two patients in the endoscopic group were outliers, with extremely large tumor volumes greater than 4 standard deviations above the mean, and were excluded from analysis. Figure is available in color online only.

TABLE 1.

Characteristics of 135 patients undergoing resection of nonfunctioning pituitary adenomas*

CharacteristicEndoscopic Surgery (n = 55)Microscopic Surgery (n = 80)p Value
Age in yrs (mean ± SD)55.9 ± 13.859.1 ± 14.60.21
Sex
 Male35 (63.6)50 (62.5)0.89
 Female20 (36.4)30 (37.5)
Prior pituitary surgery2 (3.6)11 (13.8)0.07
Length of stay in days (mean ± SD)2.3 ± 1.22.8 ± 3.40.29
Preop tumor vol in cm3 (mean ± SD)13.4 ± 14.511.0 ± 12.40.31
Preop suprasellar tumor vol in cm3 (mean ± SD)5.1 ± 7.53.3 ± 4.50.12
Knosp grade0.33
 0–249 (89.1)66 (82.5)
 3–46 (10.9)14 (17.5)
Additional tumor surgery3 (5.5)6 (7.5)0.74
Indication for surgery
 Chiasmopathy28 (50.9)45 (56.3)0.54
 Incidental finding22 (40.0)30 (37.5)0.77
 Apoplexy6 (10.9)3 (3.8)0.10
 Endocrinopathy1 (1.8)0 (0)0.23
 Other1 (1.8)4 (5.0)0.34
 Failure of medical management0 (0)1 (1.3)0.41
 Headache4 (7.3)0 (0)0.01

Values represent number (%) of patients unless otherwise indicated.

Extent of Resection

EOR, as determined on postoperative MRI scans performed within 6 months of surgery, was analyzed in 3 ways (Table 2). First, EOR was dichotomized into GTR and STR, as is most commonly reported in the medical literature. For the entire cohort, the GTR rate was 78.2% in the endoscopic group and 81.3% in the microscopic group (p = 0.67). Next, we performed formal volumetric analysis to determine the percentage of tumor removed and the volume of residual tumor. The mean percentage of tumor removed in the endoscopic and microscopic groups was 99.2% ± 1.8% and 98.7% ± 4.6% (p = 0.42), respectively, and the mean volume of residual tumor was 0.12 ± 0.31 cm3 and 0.20 ± 0.71 cm3 (p = 0.41), respectively. Figure 2 demonstrates the distribution of the percentage of tumor resection by surgical technique.

FIG. 2.
FIG. 2.

Scatterplot demonstrating the distribution of the percentage of tumor resection for endoscopic and microscopic transsphenoidal surgery.

TABLE 2.

Extent of resection of nonfunctioning pituitary adenomas by fully endoscopic and microscopic surgery

VariableNo. of PtsGTR (%)Residual Tumor Vol (cm3)*Percentage of Tumor Removed*
All patients (n = 135)
 Endoscopic surgery5578.20.12 ± 0.3199.2 ± 1.8
 Microscopic surgery8081.30.20 ± 0.7198.7 ± 4.6
 p value0.670.410.42
First-time surgery only
 Endoscopic surgery5376.50.13 ± 0.3299.2 ± 1.9
 Microscopic surgery6982.50.21 ± 0.7699.0 ± 3.4
 p value0.420.480.78
Tumor vol ≥14.31 cm3 (75th percentile)
 Endoscopic surgery1560.00.33 ± 0.5298.7 ± 2.3
 Microscopic surgery1952.60.70 ± 1.2897.0 ± 5.7
 p value0.670.270.26
Knosp Grade 0–2 tumors only
 Endoscopic surgery4983.70.06 ± 0.1699.5 ± 1.3
 Microscopic surgery6683.30.17 ± 0.6998.8 ± 4.8
 p value0.960.270.33
Knosp Grade 3–4 tumors only
 Endoscopic surgery633.30.63 ± 0.6796.9 ± 3.3
 Microscopic surgery1471.40.37 ± 0.8198.1 ± 3.7
 p value0.160.500.52
Pts = patients.

Values represent mean ± SD unless otherwise indicated.

Secondary analyses were conducted to determine whether any differences existed in EOR between the 2 techniques that accounted for confounders deemed likely to impact EOR. The subgroups we examined included patients undergoing first-time transsphenoidal surgery, patients with Knosp Grades 0–2 and 3–4, and patients with large tumors (greater than or equal to the 75th percentile in size, 14.31 cm3). No differences in EOR were found between the 2 techniques with respect to any of the 3 measures of EOR in any of these subgroups (p ≥ 0.26).

Predictors of Extent of Resection

A logistic regression model was developed to determine the primary drivers of EOR in this series of patients (Table 3). After exploratory univariate analyses to identify covariates of interest, the final multivariate model included Knosp grade, tumor size, surgical technique, and prior surgery. Tumor size was the only variable found to be predictive of EOR (p = 0.001). Patients with small tumors (defined as less than the 75th percentile, 14.31 cm3) were 5 times more likely to have complete resection compared with patients with large tumors (greater than or equal to the 75th percentile). Surgical technique and surgeon experience are not independent covariates in this study, because all the endoscopic cases were performed by the less experienced surgeon and all the microscopic cases were performed by the more experienced surgeon. Therefore, surgeon experience could not be included in the model.

TABLE 3.

Predictors of EOR of nonfunctioning pituitary adenomas by multivariate logistic regression

VariableOR95% CIp Value
Large tumor*0.190.07–0.480.001
Knosp Grade 3 or 40.410.13–1.270.12
Surgical technique1.330.51–3.460.51
Prior surgery0.590.16–2.190.43

Greater than or equal to the 75th percentile (14.31 cm3).

Endocrine Outcomes

Endocrine outcomes were compared in 2 ways: 1) on the basis of the number of patients receiving hormone supplementation at the 6-month follow-up point who were not receiving supplementation before surgery for each pituitary hormone axis (Table 4), and 2) on the basis of the number of patients receiving a diagnosis of hypopituitarism during follow-up independent of whether they were receiving hormone replacement (Table 5). No difference was found between the endoscopic and microscopic groups with respect to the number of patients receiving new hormone replacement for the adrenal, thyroid, growth hormone, or sex hormone axes (p > 0.22). This was also similar when a subgroup analysis was performed for patients who had not received prior surgery (Table 5). The percentage of patients still receiving treatment for diabetes insipidus at 6 months was higher in the microscopic group than in the endoscopic group (p = 0.04). The incidence of temporary diabetes insipidus was not tracked in the study. This finding was also similar when a subgroup analysis was performed for patients who had not received prior surgery (Table 4), with the microscopic group having a higher incidence of treatment at 6 months (p = 0.02). For the patients with a diagnosis of hypopituitarism at follow-up, independent of the receipt of any hormone replacement, no significant difference was found between the microscopic group and the endoscopic group on any of the pituitary axes (p ≥ 0.14).

TABLE 4.

Development of hypopituitarism in patients still on new hormone supplementation at 6 months after surgery for nonfunctioning pituitary adenomas*

VariableEndoscopic SurgeryMicroscopic Surgeryp Value
All cases
 No. of pts5580
 Steroid replacement7 (12.7)9 (11.3)0.79
 Thyroid replacement7 (12.7)12 (15.0)0.80
 Testosterone replacement5 (9.1)9 (11.3)0.78
 Growth hormone replacement4 (7.2)2 (2.5)0.22
 Desmopressin treatment0 (0)7 (8.8)0.04
First-time surgery cases
 No. of pts5369
 Steroid replacement7 (13.2)9 (13.0)0.98
 Thyroid replacement7 (13.2)9 (13.0)0.98
 Testosterone replacement5 (9.4)7 (10.1)0.90
 Growth hormone replacement1 (1.9)2 (2.9)0.72
 Desmopressin treatment0 (0)6 (8.7)0.02

A subset of patients with no prior history of surgery (virgin cases) was analyzed separately.

Values represent number (%) of patients unless otherwise indicated.

TABLE 5.

Development of hypopituitarism in patients with a new diagnosis of hypopituitarism still present 6 months after surgery for nonfunctioning pituitary adenomas*

No. of Pts & DiagnosisEndoscopic SurgeryMicroscopic Surgeryp Value
All cases
 No. of pts5580
 Adrenal insufficiency11 (20.0)10 (12.5)0.26
 Hypothyroidism7 (12.7)15 (18.8)0.32
 Hypogonadism10 (18.2)10 (12.8)0.39
 Growth hormone deficiency3 (5.5)6 (7.5)0.74
 Diabetes insipidus1 (1.8)7 (8.8)0.14
First-time surgery cases
 No. of pts5369
 Adrenal insufficiency11 (20.8)10 (14.5)0.36
 Hypothyroidism7 (13.2)13 (18.8)0.41
 Hypogonadism10 (18.9)8 (11.6)0.26
 Growth hormone deficiency1 (1.9)5 (7.2)0.17
 Diabetes insipidus1 (1.9)6 (8.7)0.11

A subset of patients with no prior history of surgery (virgin cases) was analyzed separately.

Values represent number (%) of patients unless otherwise indicated.

Surgical Complications

There were no significant differences in individual major complications between groups. When complications were grouped together, significantly fewer major surgical complications occurred in the endoscopic group than in the microscopic group (p = 0.02) (Table 6). Major complications in the microscopic group included 2 intracerebral hemorrhages (2.5%), 2 cerebropinal fluid (CSF) leaks requiring surgical exploration (2.5%), and 1 epistaxis (1.3%). The incidence of intraoperative CSF leak was not tracked.

TABLE 6.

Major perioperative complications after surgery for nonfunctioning pituitary adenomas exclusive of endocrine outcomes

ComplicationEndoscopic Surgery (n = 55)*Microscopic Surgery (n = 80)*p Value
Carotid artery injury0 (0)0 (0)>0.99
Intracerebral hemorrhage0 (0)2 (2.5)0.51
CSF leak requiring intervention0 (0)2 (2.5)0.51
Epistaxis0 (0)1 (1.3)>0.99
Meningitis0 (0)0 (0)>0.99
Visual worsening0 (0)0 (0)>0.99
Unplanned 30-day readmission3 (5.5)11 (13.8)0.16
Total per group3 (5.5)16 (20.0)0.02

Values represent number (%) of patients unless otherwise indicated.

The most common reason for readmission was symptomatic hyponatremia, which was found in 2 patients in the endoscopic group and in 7 in the microscopic group.

Discussion

Fully endoscopic approaches for sellar pathology have gained considerable traction among those in the neurosurgical community. The adoption of the fully endoscopic technique has occurred because of the belief that the improved visualization it offers leads to better gland preservation rates and better EOR; however, there are limited studies with high-quality objective outcomes data comparing fully endoscopic surgery to microscopebased techniques to justify this trend. As more centers have gained experience with fully endoscopic techniques, several meta-analyses and single-center experiences have been published1,6,7,10,14,16,21,23 (Table 7). The primary limitations of previous series that we have tried to address in this study are the absence of formal volumetric EOR data, experimental cohorts containing several tumor types, lack of rigorous endocrine outcomes reporting, and the fact that most published comparisons of techniques represent cases performed by a single surgeon in different surgical epochs rather than concurrently performed cases. To our knowledge, our current report is the largest series to date to compare EOR by technique and the first to use formal volumetric methods to compare techniques. In addition, the quality of our outcomes data exceeds that of most prior studies because the patients being studied were enrolled in a prospective QOL study for which they were followed closely for 6 months after surgery. Next, this study contains a concurrent series of patients managed with common institutional care pathways in a multidisciplinary pituitary center setting. Finally, this study is the first to examine the dual influences of surgical technique and surgeon experience on outcomes.

TABLE 7.

Summary of current literature comparing outcomes of microscopic and endoscopic surgery for pituitary adenomas

Authors & YearType of StudyEOR ConclusionEndocrine Outcomes ConclusionComplications ConclusionLOS Conclusion
O’Malley et al., 2008Retrospective; nonconcur-rent seriesTrend toward microscopic resection, but endoscopic resection improved w/ experienceComplete pre- & postop hormonal data not available in enough patients for analysisNo statistically significant differenceFavored endoscopic
D’Haens et al., 2009Retrospective; nonconcurrent series; functioning adenomasNAFavored endoscopic for macroadenomasFavored microscopicNA
Goudakos et al, 2011Meta-analysisNo statistically significant differenceSimilar early remission rate for functioning tumors; favored endoscopic in posterior gland preservationFavored endoscopicFavored endoscopic
Starke et al., 2013Retrospective; concurrent series; acromegalyNANo statistically significant differenceNo statistically significant differenceFavored endoscopic
Dallapiazza et al., 2014Retrospective; concurrent seriesNo statistically significant differenceNo statistically significant differenceNo statistically significant differenceFavored endoscopic
Zhu et al., 2014Meta-analysisFavored endoscopicFavored endoscopic in posterior gland preservationFavored endoscopicFavored endoscopic
Present study (Zaidi et al.)Retrospective; concurrent seriesNo statistically significant differenceFavored endoscopic in posterior gland preservationFavored endoscopicNo statistically significant difference
LOS = length of stay; NA = not available.

Extent of Tumor Resection

The most commonly reported metric for EOR in pituitary series is a dichotomized outcome of GTR versus STR. To be consistent with past series, we analyzed our experience in this manner. However, dichotomizing surgical outcomes on postoperative MRIs is problematic because of the difficulty of differentiating residual tumor from postoperative changes. To supplement this method, we also performed formal tumor volumetrics using manual segmentation, as is commonly reported in glioma tumor series.17,20 These data are most often described as “percentage of tumor resection” and “volume of residual tumor.” Using a volumetric method to determine EOR provides information about the volume of residual tumor and is particularly useful if GTR was not the intention of surgery. With these 3 methods of reporting EOR, we found no difference in mean EOR between the 2 surgical techniques even when accounting for repeat surgery and tumor anatomical characteristics such as cavernous sinus invasion and extent of suprasellar extension in a series of patients with tumor volumes less than 60 cm3. Interestingly, in multivariate analysis, the most important predictor of EOR was preoperative tumor size rather than surgical technique, which suggests that tumor characteristics are more important than the method of surgical visualization. Of note, our series contains a substantial number of patients with tumors in the volume range that is considered “large” by other authors.11

Our results parallel the findings of Dallapiazza et al.,6 who performed the only other concurrent comparison of cases involving nonfunctioning tumors. These authors noted no difference in the EOR at 1-year follow-up between a fully endoscopic technique and a sublabial microscopic technique (82% [36/44] vs 83% [25/30] GTR, p = 0.45) in a cohort of patients with Knosp Grade 0–2 tumors. Dallapiazza et al. did not perform a formal volumetric analysis of EOR but did note that patients with larger tumors and tumors with greater preoperative Knosp scores had worse GTR rates and that the endoscopic technique did not seem to confer any advantage over the microscopic technique. In contrast, Messerer et al.14 retrospectively compared resection rates for 164 patients with nonfunctioning adenomas and found that the endoscope provided a greater GTR rate than the microscope did (74% [61/82] vs 50% [41/82], respectively, p = 0.002). Their study had several limitations. First, Messerer et al. compared a sequential series of patients treated before and after conversion to a fully endoscopic approach. This approach introduces the bias of surgeon experience, as outcomes would be expected to improve during the course of a surgeon’s career,16 and it does not account for changing patterns of pituitary practice over time. Second, a GTR of 50% for the microscopic approach is lower than the rate commonly reported for that technique.15,19,22 Several meta-analyses have studied EOR. Goudakos et al.10 found no difference in the complete tumor removal rate between endoscopic and microscopic techniques. Zhu et al.23 noted improved EOR in an endoscopic cohort.

Endocrine Outcomes

EOR should be described in the context of postoperative pituitary gland function and complications. For a benign tumor like pituitary adenoma, achieving complete radiographic tumor removal may not be justified if it increases the likelihood of hypopituitarism or other complications. One challenge in interpreting endocrine outcomes in patients who have undergone resection of nonfunctioning tumors is the lack of standard reporting criteria for hypopituitarism. Most series do not define how outcomes were determined. We chose to present our data in 2 ways to give the reader as much information as possible and to be as clear and explicit as possible about how we determined the end points. First, we presented both the incidence of new hormone supplementation therapy after surgery and the incidence of hypopituitarism based on whether the patient was given a diagnosis of a deficiency. Not all patients who received a diagnosis of a hormone deficiency elected for supplementation. Second, we presented data for each hormonal axis, rather than aggregating the data into only 2 categories (i.e., “hypopituitarism” vs “normal”), as is commonly done.

Proponents of the endoscopic technique argue that improved identification of the normal pituitary gland allows for greater preservation of pituitary function than is available with the microscopic technique. We found no differences between techniques in anterior pituitary endocrine outcomes at 6-month follow-up. However, we did note a difference in preservation of the posterior gland by one measure that favored the endoscopic technique. The meta-analyses by Zhu et al.23 and Goudakos et al.10 also found a similar trend. However, Dallapiazza et al.6 found no difference between the endoscopic and microscopic techniques with respect to development of diabetes insipidus and hypocortisolism but did not report functional outcomes of other pituitary axes (thyroid, testosterone, growth hormone). Messerer et al. concluded that the endoscope provided superior endocrinological results in an analysis of a retrospectively collected database, but dichotomized outcomes as “partial anterior pituitary deficits” or as “total anterior pituitary deficits” without reporting the number of patients with hormone replacement therapy for each pituitary axis.14

Surgical Complications

As opposed to the 2D view provided by most endoscopic platforms, the microscope provides stereopsis. Advocates of the microscopic approach suggest that visuospatial awareness is imperative to avoid iatrogenic injury to critical parasellar neurovascular structures. In a recent meta-analysis of complication rates, Ammirati et al.1 found no difference between the 2 approaches in CSF leak, meningitis, visual complications, diabetes insipidus, hypopituitarism, and cranial nerve injury but did report that the endoscopic approaches had a slightly higher rate of vascular complications (1.58% vs 0.50%, p < 0.0001). This article may not provide a true assessment of surgical risk after endoscopic surgery, given that a number of endoscopic articles included in the meta-analysis were performed during the early era of endoscopic surgery (1997–2002) and a significant number of cited reports included groups outside the United States that do not require a trained neurosurgeon to be part of the surgical team. In our cohort, which was managed at a high-volume pituitary center, we found that the rate of major surgical complications when analyzed together—in categories such as carotid artery injury, CSF leak, and unplanned hospital readmission—favored the surgeon using the fully endoscopic technique. The analyses of Zhu et al.23 and Goudakos et al.10 favored endoscopic surgery, but the concurrent series presented by Starke et al.21 in acromegaly and Dallapiazza et al.6 in nonfunctioning tumors found no difference.

Surgeon Experience

As in other surgical specialties, a clear relationship between surgeon experience/surgeon volume and outcome has been demonstrated in pituitary surgery. The patients treated by more experienced surgeons have fewer complications, a lower mortality rate, and lower hospital charges.2,12,16 Our study examined patient outcomes by surgeons of differing experience who use 2 different surgical techniques but practice using a common clinical pathway. Prior to the study period, the experienced microscopic surgeon had performed nearly 2000 pituitary surgeries over 30 years. The less experienced endoscopic surgeon had performed 100 pituitary surgeries over 1 year. Our results raise the provocative question of whether certain advantages of endoscopic surgery may help a less experienced surgeon achieve outcomes similar to those of a very experienced surgeon for nonfunctioning adenomas. The advantages of endoscopic surgery that may account for this include improved magnification; superior visualization of the cavernous sinus, suprasellar space, and normal rim of the pituitary gland; and improved surgical freedom because of the use of a binostril technique.13 The relationship between surgical technique, experience, and outcomes is complex. This is particularly true in endoscopic surgery, which has a steep learning curve to achieve proficiency.3 The inflection point where the surgeon achieves sufficient proficiency with the endoscopic technique and begins to realize its benefits is not known and is likely different for each surgeon. We plan to study this question further as part of a recently initiated multicenter pituitary surgery outcomes study.

Study Limitations

Our study has several limitations. First, although preoperative variables were well matched between the 2 groups, this observational study contains biases inherent to all nonrandomized studies. Second, this study is powered to detect a medium effect size in differences of EOR between groups. To detect a small effect size, our calculations from reviewing other published reports and meta-analyses indicate that 350 patients per group would be needed. Third, this study represents a preliminary case study of the potential interaction of factors that impact outcomes—namely, surgeon experience and surgery technique. Because only 1 surgeon used each technique in this study, we are unable to separate technique and experience as covariates. Further studies are needed to determine the threshold for surgeon proficiency and whether it differs by surgery technique. Finally, our cohort represents predominantly Knosp Grade 0–2 tumors, and this limits the power of our study to investigate the efficacy of the endoscopic technique in removing tumors with cavernous sinus invasion. Other authors have suggested that the comparative value of the endoscopic technique is maximized in giant adenomas.9,13 To address the limitations of our study and those of prior series, we have initiated a prospective multicenter outcomes trial that will have greater statistical power and will sample a crosssection of centers in the United States.

Conclusions

Although endoscopic approaches for pituitary adenomas have steadily gained popularity due to improved optics, little objective data regarding EOR and endocrine outcomes have been available to justify their high adoption rate. Among a cohort of patients with nonfunctioning adenomas, a less experienced endoscopic surgeon and a more experienced microscopic surgeon yielded similar EOR, endocrine outcomes, and complications despite vastly different levels of surgeon experience. We hope that a planned prospective, multicenter trial will help to elucidate the tumor types and patient population that would benefit most from endoscopic versus microscopic resection and also further elucidate the relationship between surgeon experience, surgical technique, and outcomes.

Author Contributions

Conception and design: Little, Zaidi. Acquisition of data: Zaidi, Awad, Bohl. Analysis and interpretation of data: Little, Zaidi. Drafting the article: Little, Zaidi. Critically revising the article: Little, Zaidi, Awad, Bohl, Knecht, Jahnke, White. Reviewed submitted version of manuscript: all authors. Statistical analysis: Chapple. Administrative/technical/material support: Little. Study supervision: Little.

References

  • 1

    Ammirati MWei LCiric I: Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 84:8438492013

    • Search Google Scholar
    • Export Citation
  • 2

    Barker FG IIKlibanski ASwearingen B: Transsphenoidal surgery for pituitary tumors in the United States, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 88:470947192003

    • Search Google Scholar
    • Export Citation
  • 3

    Cappabianca PCavallo LMEsposito Fde Divitiis E: Endoscopic endonasal transsphenoidal surgery: procedure, endoscopic equipment and instrumentation. Childs Nerv Syst 20:7968012004

    • Search Google Scholar
    • Export Citation
  • 4

    Cavallo LMPrevedello DEsposito FLaws ER JrDusick JRMessina A: The role of the endoscope in the transsphenoidal management of cystic lesions of the sellar region. Neurosurg Rev 31:55642008

    • Search Google Scholar
    • Export Citation
  • 5

    Chaichana KLZaidi HPendleton CMcGirt MJGrossman RWeingart JD: The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival. Neurol Res 33:7597642011

    • Search Google Scholar
    • Export Citation
  • 6

    Dallapiazza RBond AEGrober YLouis RGPayne SCOldfield EH: Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg 121:5115172014

    • Search Google Scholar
    • Export Citation
  • 7

    D’Haens JVan Rompaey KStadnik THaentjens PPoppe KVelkeniers B: Fully endoscopic transsphenoidal surgery for functioning pituitary adenomas: a retrospective comparison with traditional transsphenoidal microsurgery in the same institution. Surg Neurol 72:3363402009

    • Search Google Scholar
    • Export Citation
  • 8

    Gendeh BSDoi MSelladurai BMKhalid BAJegan TMisiran K: The role of endoscopic endonasal approach to pituitary tumours: HUKM experience. Med J Malaysia 61:3433482006

    • Search Google Scholar
    • Export Citation
  • 9

    Gondim JAAlmeida JPAlbuquerque LAGomes EFSchops M: Giant pituitary adenomas: surgical outcomes of 50 cases operated on by the endonasal endoscopic approach. World Neurosurg 82:e281e2902014

    • Search Google Scholar
    • Export Citation
  • 10

    Goudakos JKMarkou KDGeorgalas C: Endoscopic versus microscopic trans-sphenoidal pituitary surgery: a systematic review and meta-analysis. Clin Otolaryngol 36:2122202011

    • Search Google Scholar
    • Export Citation
  • 11

    Juraschka KKhan OHGodoy BLMonsalves EKilian AKrischek B: Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas: institutional experience and predictors of extent of resection. J Neurosurg 121:75832014

    • Search Google Scholar
    • Export Citation
  • 12

    Little ASChapple KJahnke HWhite WL: Comparative inpatient resource utilization for patients undergoing endoscopic or microscopic transsphenoidal surgery for pituitary lesions. J Neurosurg 121:84902014

    • Search Google Scholar
    • Export Citation
  • 13

    McLaughlin NEisenberg AACohan PChaloner CBKelly DF: Value of endoscopy for maximizing tumor removal in endonasal transsphenoidal pituitary adenoma surgery. J Neurosurg 118:6136202013

    • Search Google Scholar
    • Export Citation
  • 14

    Messerer MDe Battista JCRaverot GKassis SDubourg JLapras V: Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal. Neurosurg Focus 30:4E112011

    • Search Google Scholar
    • Export Citation
  • 15

    Mortini PLosa MBarzaghi RBoari NGiovanelli M: Results of transsphenoidal surgery in a large series of patients with pituitary adenoma. Neurosurgery 56:122212332005

    • Search Google Scholar
    • Export Citation
  • 16

    O’Malley BW JrGrady MSGabel BCCohen MAHeuer GGPisapia J: Comparison of endoscopic and microscopic removal of pituitary adenomas: single-surgeon experience and the learning curve. Neurosurg Focus 25:6E102008

    • Search Google Scholar
    • Export Citation
  • 17

    Oppenlander MEWolf ABSnyder LABina RWilson JRCoons SW: An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg 120:8468532014

    • Search Google Scholar
    • Export Citation
  • 18

    Prevedello DMDoglietto FJane JA JrJagannathan JHan JLaws ER Jr: History of endoscopic skull base surgery: its evolution and current reality. J Neurosurg 107:2062132007

    • Search Google Scholar
    • Export Citation
  • 19

    Saito KKuwayama AYamamoto NSugita K: The transsphenoidal removal of nonfunctioning pituitary adenomas with suprasellar extensions: the open sella method and intentionally staged operation. Neurosurgery 36:6686761995

    • Search Google Scholar
    • Export Citation
  • 20

    Snyder LAWolf ABOppenlander MEBina RWilson JRAshby L: The impact of extent of resection on malignant transformation of pure oligodendrogliomas. J Neurosurg 120:3093142014

    • Search Google Scholar
    • Export Citation
  • 21

    Starke RMRaper DMPayne SCVance MLOldfleld EHJane JA Jr: Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:319031982013

    • Search Google Scholar
    • Export Citation
  • 22

    Zhang XFei ZZhang JFu LZhang ZLiu W: Management of nonfunctioning pituitary adenomas with suprasellar extensions by transsphenoidal microsurgery. Surg Neurol 52:3803851999

    • Search Google Scholar
    • Export Citation
  • 23

    Zhu MYang JWang YCao WZhu YQiu L: Endoscopic transsphenoidal surgery versus microsurgery for the resection of pituitary adenomas: a systematic review. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 49:2362392014. (Chinese)

    • Search Google Scholar
    • Export Citation

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Article Information

Contributor Notes

Correspondence Andrew S. Little, c/o Neuroscience Publications, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 350 W. Thomas Rd., Phoenix, AZ 85013. email: neuropub@dignityhealth.org.INCLUDE WHEN CITING Published online October 16, 2015; DOI: 10.3171/2015.4.JNS15102.Disclosure Dr. Little is an investor in Kogent Surgical.
Headings
Figures
  • View in gallery

    Histogram demonstrating the frequencies of preoperative tumor volumes for the endoscopic group (left side) (n = 57) and the microscopic group (right side) (n = 80) undergoing tumor resection for nonfunctioning pituitary adenomas. Two patients in the endoscopic group were outliers, with extremely large tumor volumes greater than 4 standard deviations above the mean, and were excluded from analysis. Figure is available in color online only.

  • View in gallery

    Scatterplot demonstrating the distribution of the percentage of tumor resection for endoscopic and microscopic transsphenoidal surgery.

References
  • 1

    Ammirati MWei LCiric I: Short-term outcome of endoscopic versus microscopic pituitary adenoma surgery: a systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 84:8438492013

    • Search Google Scholar
    • Export Citation
  • 2

    Barker FG IIKlibanski ASwearingen B: Transsphenoidal surgery for pituitary tumors in the United States, 1996–2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 88:470947192003

    • Search Google Scholar
    • Export Citation
  • 3

    Cappabianca PCavallo LMEsposito Fde Divitiis E: Endoscopic endonasal transsphenoidal surgery: procedure, endoscopic equipment and instrumentation. Childs Nerv Syst 20:7968012004

    • Search Google Scholar
    • Export Citation
  • 4

    Cavallo LMPrevedello DEsposito FLaws ER JrDusick JRMessina A: The role of the endoscope in the transsphenoidal management of cystic lesions of the sellar region. Neurosurg Rev 31:55642008

    • Search Google Scholar
    • Export Citation
  • 5

    Chaichana KLZaidi HPendleton CMcGirt MJGrossman RWeingart JD: The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival. Neurol Res 33:7597642011

    • Search Google Scholar
    • Export Citation
  • 6

    Dallapiazza RBond AEGrober YLouis RGPayne SCOldfield EH: Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0–2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg 121:5115172014

    • Search Google Scholar
    • Export Citation
  • 7

    D’Haens JVan Rompaey KStadnik THaentjens PPoppe KVelkeniers B: Fully endoscopic transsphenoidal surgery for functioning pituitary adenomas: a retrospective comparison with traditional transsphenoidal microsurgery in the same institution. Surg Neurol 72:3363402009

    • Search Google Scholar
    • Export Citation
  • 8

    Gendeh BSDoi MSelladurai BMKhalid BAJegan TMisiran K: The role of endoscopic endonasal approach to pituitary tumours: HUKM experience. Med J Malaysia 61:3433482006

    • Search Google Scholar
    • Export Citation
  • 9

    Gondim JAAlmeida JPAlbuquerque LAGomes EFSchops M: Giant pituitary adenomas: surgical outcomes of 50 cases operated on by the endonasal endoscopic approach. World Neurosurg 82:e281e2902014

    • Search Google Scholar
    • Export Citation
  • 10

    Goudakos JKMarkou KDGeorgalas C: Endoscopic versus microscopic trans-sphenoidal pituitary surgery: a systematic review and meta-analysis. Clin Otolaryngol 36:2122202011

    • Search Google Scholar
    • Export Citation
  • 11

    Juraschka KKhan OHGodoy BLMonsalves EKilian AKrischek B: Endoscopic endonasal transsphenoidal approach to large and giant pituitary adenomas: institutional experience and predictors of extent of resection. J Neurosurg 121:75832014

    • Search Google Scholar
    • Export Citation
  • 12

    Little ASChapple KJahnke HWhite WL: Comparative inpatient resource utilization for patients undergoing endoscopic or microscopic transsphenoidal surgery for pituitary lesions. J Neurosurg 121:84902014

    • Search Google Scholar
    • Export Citation
  • 13

    McLaughlin NEisenberg AACohan PChaloner CBKelly DF: Value of endoscopy for maximizing tumor removal in endonasal transsphenoidal pituitary adenoma surgery. J Neurosurg 118:6136202013

    • Search Google Scholar
    • Export Citation
  • 14

    Messerer MDe Battista JCRaverot GKassis SDubourg JLapras V: Evidence of improved surgical outcome following endoscopy for nonfunctioning pituitary adenoma removal. Neurosurg Focus 30:4E112011

    • Search Google Scholar
    • Export Citation
  • 15

    Mortini PLosa MBarzaghi RBoari NGiovanelli M: Results of transsphenoidal surgery in a large series of patients with pituitary adenoma. Neurosurgery 56:122212332005

    • Search Google Scholar
    • Export Citation
  • 16

    O’Malley BW JrGrady MSGabel BCCohen MAHeuer GGPisapia J: Comparison of endoscopic and microscopic removal of pituitary adenomas: single-surgeon experience and the learning curve. Neurosurg Focus 25:6E102008

    • Search Google Scholar
    • Export Citation
  • 17

    Oppenlander MEWolf ABSnyder LABina RWilson JRCoons SW: An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg 120:8468532014

    • Search Google Scholar
    • Export Citation
  • 18

    Prevedello DMDoglietto FJane JA JrJagannathan JHan JLaws ER Jr: History of endoscopic skull base surgery: its evolution and current reality. J Neurosurg 107:2062132007

    • Search Google Scholar
    • Export Citation
  • 19

    Saito KKuwayama AYamamoto NSugita K: The transsphenoidal removal of nonfunctioning pituitary adenomas with suprasellar extensions: the open sella method and intentionally staged operation. Neurosurgery 36:6686761995

    • Search Google Scholar
    • Export Citation
  • 20

    Snyder LAWolf ABOppenlander MEBina RWilson JRAshby L: The impact of extent of resection on malignant transformation of pure oligodendrogliomas. J Neurosurg 120:3093142014

    • Search Google Scholar
    • Export Citation
  • 21

    Starke RMRaper DMPayne SCVance MLOldfleld EHJane JA Jr: Endoscopic vs microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:319031982013

    • Search Google Scholar
    • Export Citation
  • 22

    Zhang XFei ZZhang JFu LZhang ZLiu W: Management of nonfunctioning pituitary adenomas with suprasellar extensions by transsphenoidal microsurgery. Surg Neurol 52:3803851999

    • Search Google Scholar
    • Export Citation
  • 23

    Zhu MYang JWang YCao WZhu YQiu L: Endoscopic transsphenoidal surgery versus microsurgery for the resection of pituitary adenomas: a systematic review. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 49:2362392014. (Chinese)

    • Search Google Scholar
    • Export Citation
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