- Email: [email protected]
Safety and Outcome of Transsphenoidal Pituitary Adenoma Resection in Elderly Patients
Original Article
Safety and Outcome of Transsphenoidal Pituitary Adenoma Resection in Elderly Patients Mohammed A. Azab1, Molly O’Hagan2, Hussam Abou-Al-Shaar1,3, Michael Karsy1, Jian Guan1, William T. Couldwell1
OBJECTIVE: Pituitary adenomas account for 10%e20% of intracranial brain tumors but have greater incidence in elderly patients. We assessed microsurgical treatment for pituitary adenomas in this population.
-
METHODS: A retrospective cohort of patients ‡60 years of age was identified. Patients were divided into deciles by age for evaluation of variables affecting outcome: 60e70 (group 1), 71e80 (group 2), and >80 years (group 3).
-
RESULTS: Two hundred five patients were identified among group 1 (n [ 131), group 2 (n [ 65), and group 3 (n [ 9). Preoperative variables other than age did not differ. Most patients presented with visual disturbance, in 56.5%, 73.8%, and 50% in groups 1, 2, and 3, respectively. The next most common indication was headache, followed by endocrinopathy. Tumors were overwhelmingly nonfunctional (P [ 0.97) and macroadenomas (P [ 0.5) in all 3 groups. Gross total resection occurred in 56.9%e80% of patients, and this rate did not differ among groups. Complication rates of 6.9% in group 1, 9.2% in group 2, and 0.0% in group 3 were observed (P [ 0.8). No perioperative mortality was identified. Mean length of follow-up ranged from 8.9 to 28.3 months.
-
CONCLUSIONS: In this series of microsurgical resection of pituitary adenomas in elderly patients, good efficacy and safety of treatment were observed. Preclusion of surgical treatment, including open resection, simply because of age is not warranted and instead a comprehensive evaluation of a patient’s risk profile and surgical goals should be undertaken.
-
INTRODUCTION
T
he evaluation of neurosurgical procedures in the elderly population recently has received significant attention in the literature.1 The number of elderly patients, defined by the World Health Organization as those 65 years of age, is projected to increase by 2.9% annually until 2050, increasing from 562 million in 2012 to approximately 1.6 billion in 2050.2 Elderly patient frailty, as a measure of recovery from neurosurgical illness or disease, has received significant attention.3,4 Elderly patients are increasingly susceptible to potentially poorer outcomes because of greater rates of comorbidities, limited nutrition, and poor tolerance for surgical complications. Pituitary adenomas account for 10%e20% of intracranial tumors but have greater incidence in elderly patients.5 Multiple early studies suggested a greater rate of perioperative and postoperative complication associated with resection of pituitary adenomas in older patients.6-10 These complications can include greater rates of cerebrospinal fluid (CSF) leak, postoperative hormone dysfunction, and visual deficits. Previous studies have aimed to evaluate the role of microsurgical (MS) resection6-20 and endoscopic, endonasal (EE) resection21-25 of pituitary adenomas. One study showed equivalent outcome and safety in elderly patients after MS and EE resection.26 MS resection has undergone continued refinement over the last 2e3 decades, in terms of microscope capabilities, preoperative imaging, and perioperative management of surgical complications. In addition, improved nonoperative and radiosurgical management of pituitary adenomas raises the question of which is the optimal treatment of pituitary adenomas in elderly patients. We evaluated the efficacy and safety after MS resection for pituitary adenomas in elderly patients and specifically the correlation of complications and outcomes with increased age.
Key words Elderly - Pituitary adenoma - Safety - Transsphenoidal approach
From the 1Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah; 2Department of Neurosurgery, New York Medical College, Valhalla, New York; and 3Department of Neurosurgery, Hofstra Northwell School of Medicine, Manhasset, New York, USA
Abbreviations and Acronyms CSF: Cerebrospinal fluid EE: Endoscopic, endonasal GTR: Gross total resection MS: Microsurgical
Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.024
-
To whom correspondence should be addressed: William T. Couldwell, M.D., Ph.D. [E-mail: [email protected]]
Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY -: e1-e7, - 2018
www.WORLDNEUROSURGERY.org
e1
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
METHODS Data Acquisition After receiving institutional board review approval, we undertook a retrospective cohort study of patients who underwent a MS transsphenoidal approach for resection of pituitary adenoma. All patients who underwent resection from February 14, 2002, to May 2, 2017, were identified. Subsequently, cases were narrowed to patients with ages 60 years. Patients with nonpituitary lesions or with inadequate data were excluded from analysis. Patients were divided into groups 1 through 3 depending on age: 60e70 (group 1), 71e80 (group 2), and >80 years (group 3). Demographic and surgical characteristics were reviewed, including patient age, sex, and body mass index, symptoms prompting surgical presentation, tumor type, tumor size, previous pituitary tumor resection, pre- and postoperative hormone use, tumor recurrence, length of follow-up, use of endoscope, fat/fascia use, CSF diversion (e.g., multiple lumbar punctures or lumbar drain), surgery date, operative time (as determined from stated in and out room times), and estimated blood loss. Complications were reviewed, including all unanticipated intraoperative and postoperative events. Hormone supplementation pre- or postoperatively regardless of duration was noted. Gross total resection (GTR) was defined as the removal of all visible tumor on T1weighted contrast-enhanced imaging. An endoscope is used in specific cases to ensure adequate tumor removal. Statistical Analysis Continuous variables were described as a mean standard deviation, whereas discrete variables were described as frequency (% of total). Continuous and discrete variables were analyzed via the t test and c2 test, respectively. A P value <0.05 was considered statistically significant. Data were analyzed using SPSS (version 20.0; IBM, Armonk, New York, USA).
macroadenomas, including 83.2% in group 1, 83.1% in group 2, and 80.0% in group 3 (P ¼ 0.5). GTR was achieved in a total of 67.2%, 56.9%, and 80.0% of adenomas in groups 1, 2, and 3, respectively (P ¼ 0.7). An overall GTR of 64.9% was seen for the elderly population. No differences in operative room time (P ¼ 0.1), estimated blood loss (P ¼ 0.8), endoscope use (P ¼ 0.7), fat/fascia use (P ¼ 0.4), or CSF diversion (P ¼ 0.1) were observed among groups. The preoperative hormone use rates of 29.8% in group 1, 29.2% in group 2, and 30.0% in group 3 did not differ (P ¼ 0.995), nor did the rates of postoperative hormone use (P ¼ 0.6). There was a significant increase in hormone use postoperatively in groups 1 (P ¼ 0.003) and 2 (P ¼ 0.05), but not group 3 (P ¼ 0.2) (c2 test). Patient complication rates also were similar regardless of patient age, with a rate of 6.1% in group 1, 9.2% in group 2, and 0.0% in group 3 patients (P ¼ 0.8). An overall complication rate of 6.8% was seen in the entire cohort. The mean length of follow-up (P ¼ 0.2) and tumor recurrence rate (P ¼ 0.8) were also similar in all patient age groups. DISCUSSION Study Findings The results of this study support the safety and efficacy of MS resection during the treatment of pituitary adenomas in elderly patients. Overall GTR rates of 56.9%e80% were seen in patients >60 years of age depending on age decile, without any statistically significant differences among the 3 groups (Table 1). No difference in operative room time or estimated blood loss was seen among elderly patients of different ages. The rate of patient complications ranged from 0% to 9.2%, which was statistically similar in all age deciles. There were no deaths associated with MS resection in this series. These findings indicate that age alone should not be exclusionary as age did not correlate with outcomes.
RESULTS A total of 634 patients who underwent MS resection for pituitary adenoma were retrospectively identified. For the purposes of this study, these were limited to 205 elderly patients, who were divided into 3 groups: between 60 and 70 years (n ¼ 131), 71e80 years (n ¼ 65), and >80 (n ¼ 9) (Table 1). The mean ages for groups 1, 2, and 3 were 65.2 3.2 years, 74.3 3.0 years, and 83.6 3.0 years, respectively (Table 1, Figure 1). The groups differed only in age. Most patients were male, including 53.4% of group 1, 69.2% of group 2, and 60.0% of group 3 patients (P ¼ 0.2). Patient body mass index was similar among groups (P ¼ 0.5). The most common presenting symptom was visual dysfunction, occurring in 56.5% of patients in group 1, 73.8% in group 2, and 50.0% in group 3. The next most common symptom was headache, including 33.6% of patients in group 1, 36.9% in group 2, and 20.0% in group 3. There was a greater incidence of incidental adenomas (30.0%) in group 3 patients compared with group 1 (14.5%) and group 2 (7.7%); however, there were no significant differences in overall symptomatology (P ¼ 0.2). Most tumors were nonfunctional adenomas, including 76.3% in group 1, 78.5% in group 2, and 90.0% in group 3 (P ¼ 0.97). In addition, most tumors were
e2
www.SCIENCEDIRECT.com
Modern Treatment of Pituitary Adenomas in Elderly Patients Multiple studies have evaluated the role of MS resection in elderly patients with pituitary adenoma (Table 2). Earlier studies suggested efficacy in tumor resection but significant rates of complications in elderly patients.6-10,27 However, later studies evaluating MS resection began showing improved efficacy and safety after MS resection in elderly patients.11,12,15,18 Hong et al.12 evaluated 103 patients aged 65 years and demonstrated GTR in 47.6% of cases. Complications included transient diabetes insipidus in 37.9%, CSF leaks in 4.9%, permanent visual dysfunction in 1.9%, and postoperative hypopituitarism in 10.7%. Sheehan et al.18 evaluated 64 patients 70 years and reported a mean length of stay of 2.6 days, with a 12.5% rate of new postoperative hormonal deficits and no surgery-related deaths. These more recent results are in line with our current findings showing GTR rates from 67.2% to 80% and complication rates from 0.0% to 9.2% (overall 6.8%). Moreover, although complications varied with age group in our study, the rates were not statistically significantly different. Thus, our results reflect high success rates in surgical GTR for most tumors regardless of age.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.024
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
Table 1. Demographic and Surgical Characteristics for Elderly Patients Undergoing Transsphenoidal Resections of Pituitary Adenomas Variable Age, years, mean SD
Group 1, 60e70 years, n [ 131
Group 2, 71e80 years, n [ 65
Group 3, >80 years, n [ 10
P Value
65.2 3.2
74.3 3.0
83.6 3.0
0.0001
Sex (males), % total
70 (53.4%)
45 (69.2%)
6 (60.0%)
0.2
Body mass index, kg/m2, mean SD
30.5 6.3
29.6 5.5
28.7 3.2
0.5
Symptoms, % total
0.2
Visual disturbance
74 (56.5%)
48 (73.8%)
5 (50.0%)
Incidental
19 (14.5%)
5 (7.7%)
3 (30.0%)
Apoplexy
14 (10.7%)
11 (16.9%)
1 (10.0%)
Endocrinopathy
29 (22.1%)
15 (23.1%)
1 (10.0%)
Headache
44 (33.6%)
24 (36.9%)
2 (20.0%)
5 (3.8%)
0 (0.0%)
1 (10.0%)
Failure of medical management Pituitary tumor type, % total Nonfunctional adenoma
0.97 100 (76.3%)
51 (78.5%)
9 (90.0%)
Prolactinoma
6 (4.6%)
2 (3.1%)
0 (0.0%)
Growth hormone
5 (3.8%)
3 (4.6%)
0 (0.0%)
Cortisol-secreting
2 (1.5%)
1 (1.5%)
0 (0.0%)
Other/atypical
7 (5.3%)
2 (3.1%)
1 (10.0%)
Unknown
11 (8.4%)
6 (9.2%)
0 (0.0%)
Microadenoma
13 (9.9%)
7 (10.8%)
1 (10.0%)
Macroadenoma
109 (83.2%)
54 (83.1%)
8 (80.0%)
Giant adenoma
2 (1.5%)
3 (4.6%)
1 (10.0%)
Unknown
7 (5.3%)
1 (1.5%)
0 (0.0%)
Endocrinologic normalization, % total
108 (82.4%)
48 (73.8%)
9 (90.0%)
0.5
Gross total resection, % total
88 (67.2%)
37 (56.9%)
8 (80.0%)
0.7
Tumor size, % total
Room time, hours, mean SD
0.5
3.2 0.9
3.3 0.9
2.6 0.7
0.1
121.4 253.7
136.9 178.8
73.6 59.5
0.8
Endoscope use, % total
9 (6.9%)
5 (7.7%)
0 (0.0%)
0.7
Fat/fascia use, % total
88 (67.2%)
49 (75.4%)
7 (70.0%)
0.4
Estimated blood loss, mL, mean SD
CSF diversion, % total None
0.1 112 (85.5%)
55 (84.6%)
7 (70.0%)
Lumbar puncture
8 (6.1%)
3 (4.6%)
3 (30.0%)
Lumbar drain
3 (2.3%)
4 (6.2%)
0 (0.0%)
8 (6.1%)
3 (4.6%)
0 (0.0%)
Any preoperative hormone use, % total
Unknown
39 (29.8%)
19 (29.2%)
3 (30.0%)
0.995
Any postoperative hormone use, % total
63 (48.1%)
30 (46.2%)
6 (60.0%)
0.6
3 (2.3%)
6 (9.2%)
0 (0.0%)
0.08
Return to OR, % total
Bold value indicates statistically significant. SD, standard deviation; CSF, cerebrospinal fluid; OR, operating room; ICA, internal carotid artery. *Two deaths were reported in this group at last follow-up but were not due to the transsphenoidal surgery.
WORLD NEUROSURGERY -: e1-e7, - 2018
Continues
www.WORLDNEUROSURGERY.org
e3
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
Table 1. Continued Variable Any complication, % total CSF leak
Group 1, 60e70 years, n [ 131
Group 2, 71e80 years, n [ 65
Group 3, >80 years, n [ 10
P Value
8 (6.1%)
6 (9.2%)
0 (0.0%)
0.8
3 (2.3%)
3 (4.6%)
0 (0.0%)
Meningitis
2 (1.5%)
0 (0.0%)
0 (0.0%)
Cranial hematoma
0 (0.0%)
1 (1.5%)
0 (0.0%)
ICA injury
1 (0.8%)
1 (1.5%)
0 (0.0%)
Postoperative epistaxis
2 (1.5%)
0 (0.0%)
0 (0.0%)
Death
0 (0.0%)*
0 (0.0%)
0 (0.0%)
0 (0.0%)
1 (1.5%)
0 (0.0%)
Follow-up, months, mean SD
Readmission within 30 days
28.3 33.5
22.7 30.2
8.9 9.1
0.2
Recurrence on follow-up, % total
6 (4.6%)
3 (4.6%)
0 (0.0%)
0.8
52.3 72.4
43.4 39.9
e
0.7
Time until recurrence, months, SD
Bold value indicates statistically significant. SD, standard deviation; CSF, cerebrospinal fluid; OR, operating room; ICA, internal carotid artery. *Two deaths were reported in this group at last follow-up but were not due to the transsphenoidal surgery.
Comparison of the MS and EE Approaches in Elderly Patients With the improved efficacy of the EE approach, a strong desire to compare MS and EE approaches in elderly patients has been seen specifically for pituitary adenomas as a possible way of improving safety and efficacy. Pereira et al.26 evaluated 102 patients 70 years who underwent MS (48.1%) or EE (51.9%) for pituitary adenoma resection. A total of 79% of patients had improved or stable endocrine function, and 91% showed improved or stable visual deficits. No difference in outcomes or complications was seen between patients who underwent MS compared with EE. Some studies have shown good safety with the EE approach in elderly patients,20 whereas others have shown greater complication rates, specifically perioperative medical
Figure 1. Distribution of patient age for the entire cohort of patients (A) and of elderly patients (60
e4
www.SCIENCEDIRECT.com
complications, in elderly patients.24 Gondim et al.23 evaluated 603 patients, with 493 <60 years of age and 110 60 years of age who underwent EE resection. GTR rates of 76.6% in patients 60e69 years and 78.2% in patients 70e84 years of age were observed. Overall complication rates were 20.0% and 32.7% in patients age 60e69 years or 70e84 years, respectively, which were significantly greater than the 10.0% overall complication rate in patients <60 years of age (P < 0.05). These results suggest that an EE approach would not simply be more efficacious in the elderly population compared with a MS approach. In addition, the use of the EE approach in our own experience is associated with longer operative and anesthetic times (W.T. Couldwell, unpublished data).
years) (B) treated with transsphenoidal approaches for pituitary adenoma resection.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.024
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
Table 2. Summary of Studies of Transsphenoidal Surgery in Elderly Patients Reference
Age Cutoff, years
Sample Size
Gross Total Resection Rate
Complication Rate
Puchner et al., 19956
65
15
100%*
0.0%
7
Benbow et al., 1997
65
44
Fraioli et al., 19998
70
11
65
84
10
Kurosaki et al., 2000
70
32
Kurosaki et al., 200127
80
15
Ferrante et al., 200211
70
39
Letournel et al., 200328
65
59
Del Monte et al., 200729
65
27
9
Turner et al., 1999
34.4% complication; 9.1% death 54.4%
0.0%
75.0%
0.0%
0.0%
29.6%
70
64
Hong et al., 200812
65
103
68.9%
Locatelli et al., 201315
65
43
54%
Yunoue et al., 201419
80
10
26
70
102
79.0%
1.9% hypotension; 2.9% transfusion; 9.6% transient DI; 8.7% SIADH; 0.9% CSF leak; 0% death
65
38
61.0%
0.0%
70
55
68.7%
9% CSF leak; 3.6% permanent DI; 7.2% hypertension; 1.8% myocardial ischemia; 1.8% death
65
25
Zhan et al., 2015
65
158
75.9%
Transient DI 17.8%; permanent DI 4.4%; CSF leak 6.4%
Liu et al., 201514
65
158
Zhao et al., 2017
65
130
Fujimoto et al., 201722
80
12
80
15
53.3% 65 years; 73.5% 80 years
0.0%
Wilson et al., 2018
70
54
70.4%
7.4% 60e69 years; 18.5% 70 years
Sasagawa et al., 201817
65
24
67.0%
17.0%
Sheehan et al., 2008
18
Pereira et al., 2014
Robenshtok et al., 201416 Gondim et al., 2015
23
Marenco et al., 201530 25
20
21
Chinezu et al., 2017
24
0.0%
0.0% 0.0%
4.3%
25.0% CSF leak
DI, diabetes insipidus; SIADH, syndrome of inappropriate antidiuretic hormone secretion; CSF, cerebrospinal fluid. *Normalization of growth hormone levels (<4.5 mg/L) for all patients seen.
Nuances of Pituitary Adenomas in Elderly Patients Management of pituitary tumors in elderly patients is further complicated by nuances of neurosurgical management and medical comorbidities.31-37 Kinoshita et al.13 performed a meta-analysis of 32 studies from 2000 to 2018 containing the key words “pituitary adenoma” and “elder” OR “elderly.” The definition of “elderly” varied from 65 years of age to 80 years of age. Elderly patients commonly presented with nonfunctional tumors but also showed tumor sizes that were similar to those of younger patients reported in the literature. Greater rates of ophthalmoplegia from mass effect in elderly patients were reported compared with younger patients. Increased numbers of comorbid conditions, greater American Society of Anesthesia physical status classification grade, and greater Charlson comorbidity index were reported. Perioperative mortality was low but did increase in some studies with older age groups. Patient morbidity, specifically
WORLD NEUROSURGERY -: e1-e7, - 2018
postoperative hematoma, CSF leak, postoperative hyponatremia, and hormone dysfunction, also increased in older ages. Tumor recurrence was less likely in elderly patients compared with younger patients. Tumor resection rates were similar, with a range of 71%e100% of patients showing improvement of visual symptoms. Our study also supports these findings, showing that modern MS resection can be safe and effective. We did not, however, find worse outcomes in older patients. Visual disturbances as a primary presenting feature of pituitary adenomas in elderly patients often can be misleading and result in delay of diagnosis if elderly patients are worked up for other ophthalmologic issues (e.g., glaucoma, macular degeneration, cataracts). Similarly, the increased rate of pre- and postoperative hormonal dysfunction suggests that greater attention to evaluation and supplementation is required in the elderly population. Overall, the diagnosis of pituitary
www.WORLDNEUROSURGERY.org
e5
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
adenomas in elderly patients seems to require a high index of suspicion while the operative treatment involves recognition of perioperative comorbidities.
been previously reported by our group38,39 and was not the focus of this specific study. CONCLUSIONS
Limitations This is a single-center study, performed by an experienced single neurosurgeon; thus, one limitation may be in the generalizability of these findings to other centers. No EE cohort was used for comparison. Similarly, we did not assess postoperative clinical outcome by standardized visual field examination or quality-of-life measures, which makes evaluation of surgical efficacy difficult. Finally, this is a retrospective cohort study, where safety and efficacy may be biased by patient selection and inclusion. We did not specifically compare a patient cohort <60 years since this has
REFERENCES 1. Moncef B, Pierre K. Brain and Spine Surgery in the Elderly. Cham, Switzerland: Springer International Publishing; 2017. 2. He W, Goodkind D, Kowal P. An Aging World: 2015. Washington, DC: U.S. Census Bureau, International Population Reports, P95/16e1; 2016. 3. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752-762. 4. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173:489-495. 5. McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA. Demographic differences in incidence for pituitary adenoma. Pituitary. 2011;14:23-30.
The results of our study support the safety and efficacy of MS resection on pituitary adenomas in elderly patients. Age alone should not be an exclusionary criterion in the treatment of these patients. The selection of this approach, however, highly depends on patient-specific factors, attending preference, and institutional resources. ACKNOWLEDGMENTS We thank Kristin Kraus, MSc, for her editorial assistance.
transsphenoidal surgery and follow-up. J Clin Neurosci. 2008;15:1091-1095. 13. Kinoshita Y, Kurisu K, Arita K. Nonfunctioning pituitary adenomas in elderly patients. J Clin Neurosci. 2018;53:127-131. 14. Liu J, Li C, Xiao Q, et al. Comparison of pituitary adenomas in elderly and younger adults: clinical characteristics, surgical outcomes, and prognosis. J Am Geriatr Soc. 2015;63:1924-1930. 15. Locatelli M, Bertani G, Carrabba G, et al. The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk. Pituitary. 2013; 16:146-151. 16. Robenshtok E, Benbassat CA, Hirsch D, et al. Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly compared with younger age groups. Endocr Pract. 2014;20:159-164.
6. Puchner MJ, Knappe UJ, Ludecke DK. Pituitary surgery in elderly patients with acromegaly. Neurosurgery. 1995;36:677-683 [discussion: 683684].
17. Sasagawa Y, Hayashi Y, Tachibana O, et al. Transsphenoidal surgery for elderly patients with acromegaly and its outcomes: comparison with younger patients. World Neurosurg. 2018;118: e229-e234.
7. Benbow SJ, Foy P, Jones B, Shaw D, MacFarlane IA. Pituitary tumours presenting in the elderly: management and outcome. Clin Endocrinol (Oxf). 1997;46:657-660.
18. Sheehan JM, Douds GL, Hill K, Farace E. Transsphenoidal surgery for pituitary adenoma in elderly patients. Acta Neurochir (Wien). 2008;150: 571-574 [discussion: 574].
8. Fraioli B, Pastore FS, Signoretti S, De Caro GM, Giuffre R. The surgical treatment of pituitary adenomas in the eighth decade. Surg Neurol. 1999;51: 261-266 [discussion: 266-267].
19. Yunoue S, Tokimura H, Tominaga A, et al. Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older. Neurosurg Rev. 2014;37:269-276 [discussion: 276-277].
9. Turner HE, Adams CB, Wass JA. Pituitary tumours in the elderly: a 20 year experience. Eur J Endocrinol. 1999;140:383-389.
20. Zhao Y, Lian W, Xing B, et al. The clinical characteristics and microsurgical therapy of pituitary adenomas in elderly patients: a retrospective study of 130 cases. J Clin Neurosci. 2017;46:13-16.
10. Kurosaki M, Ludecke DK, Flitsch J, Saeger W. Surgical treatment of clinically nonsecreting pituitary adenomas in elderly patients. Neurosurgery. 2000;47:843-848 [discussion: 848-849]. 11. Ferrante L, Trillo G, Ramundo E, et al. Surgical treatment of pituitary tumors in the elderly: clinical outcome and long-term follow-up. J Neurooncol. 2002;60:185-191. 12. Hong J, Ding X, Lu Y. Clinical analysis of 103 elderly patients with pituitary adenomas:
e6
www.SCIENCEDIRECT.com
21. Chinezu R, Fomekong F, Lasolle H, et al. Risks and benefits of endoscopic transsphenoidal surgery for nonfunctioning pituitary adenomas in patients of the ninth decade. World Neurosurg. 2017; 106:315-321. 22. Fujimoto K, Yano S, Shinojima N, Hide T, Kuratsu JI. Endoscopic endonasal transsphenoidal surgery for patients aged over 80 years with pituitary adenomas: surgical and follow-up results. Surg Neurol Int. 2017;8:213.
23. Gondim JA, Almeida JP, de Albuquerque LA, Gomes E, Schops M, Mota JI. Endoscopic endonasal transsphenoidal surgery in elderly patients with pituitary adenomas. J Neurosurg. 2015;123: 31-38. 24. Wilson PJ, Omay SB, Kacker A, Anand VK, Schwartz TH. Endonasal endoscopic pituitary surgery in the elderly. J Neurosurg. 2018;128: 429-436. 25. Zhan R, Ma Z, Wang D, Li X. Pure endoscopic endonasal transsphenoidal approach for nonfunctioning pituitary adenomas in the elderly: surgical outcomes and complications in 158 patients. World Neurosurg. 2015;84:1572-1578. 26. Pereira EA, Plaha P, Chari A, et al. Transsphenoidal pituitary surgery in the elderly is safe and effective. Br J Neurosurg. 2014;28:616-621. 27. Kurosaki M, Saeger W, Ludecke DK. Pituitary tumors in the elderly. Pathol Res Pract. 2001;197: 493-497. 28. Letournel F, Menei P, Guy G, Saint-Andre JP. Transsphenoidal surgery in the elderly. J Am Geriatr Soc. 2003;51:729-730. 29. Del Monte P, Foppiani L, Ruelle A, et al. Clinically non-functioning pituitary macroadenomas in the elderly. Aging Clin Exp Res. 2007;19:34-40. 30. Marenco HA, Zymberg ST, Santos Rde P, Ramalho CO. Surgical treatment of non-functioning pituitary macroadenomas by the endoscopic endonasal approach in the elderly. Arq Neuropsiquiatr. 2015;73:764-769. 31. Taussky P, Kalra R, Coppens J, Mohebali J, Jensen R, Couldwell WT. Endocrinological outcome after pituitary transposition (hypophysopexy) and adjuvant radiotherapy for tumors involving the cavernous sinus. J Neurosurg. 2011; 115:55-62. 32. Liu JK, Weiss MH, Couldwell WT. Surgical approaches to pituitary tumors. Neurosurg Clin N Am. 2003;14:93-107. 33. Liu JK, Orlandi RR, Apfelbaum RI, Couldwell WT. Novel closure technique for the endonasal transsphenoidal approach. Technical note. J Neurosurg. 2004;100:161-164.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.024
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
34. Hornyak M, Couldwell WT. Multimodality treatment for invasive pituitary adenomas. Postgrad Med. 2009;121:168-176. 35. Couldwell WT, Weiss MH, Rabb C, Liu JK, Apfelbaum RI, Fukushima T. Variations on the standard transsphenoidal approach to the sellar region, with emphasis on the extended approaches and parasellar approaches: surgical experience in 105 cases. Neurosurgery. 2004;55:539-547 [discussion: 547550].
prolactinomas. Neurosurg Clin N Am. 2003;14: 89-92. vii.
outcomes after transsphenoidal resection of sellar tumors. Neurosurgery. 2018;83:726-731.
37. Couldwell WT. Transsphenoidal and transcranial surgery for pituitary adenomas. J Neurooncol. 2004; 69:237-256.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
38. Karsy M, Bowers CA, Scoville J, et al. Evaluation of complications and costs during overlapping transsphenoidal surgery in the treatment of pituitary adenoma [E-pub ahead of print]. Neurosurgery. https://doi.org/10.1093/ neuros/nyy269, Accessed August 9, 2018.
Received 24 August 2018; accepted 4 November 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.024 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
36. Couldwell WT, Rovit RL, Weiss MH. Role of surgery in the treatment of micro-
39. Guan J, Karsy M, Bisson EF, Couldwell WT. Patient-level factors influencing of hospital costs and short-term patient-reported
WORLD NEUROSURGERY -: e1-e7, - 2018
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
www.WORLDNEUROSURGERY.org
e7
Safety and Outcome of Transsphenoidal Pituitary Adenoma Resection in Elderly Patients Mohammed A. Azab1, Molly O’Hagan2, Hussam Abou-Al-Shaar1,3, Michael Karsy1, Jian Guan1, William T. Couldwell1
OBJECTIVE: Pituitary adenomas account for 10%e20% of intracranial brain tumors but have greater incidence in elderly patients. We assessed microsurgical treatment for pituitary adenomas in this population.
-
METHODS: A retrospective cohort of patients ‡60 years of age was identified. Patients were divided into deciles by age for evaluation of variables affecting outcome: 60e70 (group 1), 71e80 (group 2), and >80 years (group 3).
-
RESULTS: Two hundred five patients were identified among group 1 (n [ 131), group 2 (n [ 65), and group 3 (n [ 9). Preoperative variables other than age did not differ. Most patients presented with visual disturbance, in 56.5%, 73.8%, and 50% in groups 1, 2, and 3, respectively. The next most common indication was headache, followed by endocrinopathy. Tumors were overwhelmingly nonfunctional (P [ 0.97) and macroadenomas (P [ 0.5) in all 3 groups. Gross total resection occurred in 56.9%e80% of patients, and this rate did not differ among groups. Complication rates of 6.9% in group 1, 9.2% in group 2, and 0.0% in group 3 were observed (P [ 0.8). No perioperative mortality was identified. Mean length of follow-up ranged from 8.9 to 28.3 months.
-
CONCLUSIONS: In this series of microsurgical resection of pituitary adenomas in elderly patients, good efficacy and safety of treatment were observed. Preclusion of surgical treatment, including open resection, simply because of age is not warranted and instead a comprehensive evaluation of a patient’s risk profile and surgical goals should be undertaken.
-
INTRODUCTION
T
he evaluation of neurosurgical procedures in the elderly population recently has received significant attention in the literature.1 The number of elderly patients, defined by the World Health Organization as those 65 years of age, is projected to increase by 2.9% annually until 2050, increasing from 562 million in 2012 to approximately 1.6 billion in 2050.2 Elderly patient frailty, as a measure of recovery from neurosurgical illness or disease, has received significant attention.3,4 Elderly patients are increasingly susceptible to potentially poorer outcomes because of greater rates of comorbidities, limited nutrition, and poor tolerance for surgical complications. Pituitary adenomas account for 10%e20% of intracranial tumors but have greater incidence in elderly patients.5 Multiple early studies suggested a greater rate of perioperative and postoperative complication associated with resection of pituitary adenomas in older patients.6-10 These complications can include greater rates of cerebrospinal fluid (CSF) leak, postoperative hormone dysfunction, and visual deficits. Previous studies have aimed to evaluate the role of microsurgical (MS) resection6-20 and endoscopic, endonasal (EE) resection21-25 of pituitary adenomas. One study showed equivalent outcome and safety in elderly patients after MS and EE resection.26 MS resection has undergone continued refinement over the last 2e3 decades, in terms of microscope capabilities, preoperative imaging, and perioperative management of surgical complications. In addition, improved nonoperative and radiosurgical management of pituitary adenomas raises the question of which is the optimal treatment of pituitary adenomas in elderly patients. We evaluated the efficacy and safety after MS resection for pituitary adenomas in elderly patients and specifically the correlation of complications and outcomes with increased age.
Key words Elderly - Pituitary adenoma - Safety - Transsphenoidal approach
From the 1Department of Neurosurgery, Clinical Neurosciences Center, University of Utah, Salt Lake City, Utah; 2Department of Neurosurgery, New York Medical College, Valhalla, New York; and 3Department of Neurosurgery, Hofstra Northwell School of Medicine, Manhasset, New York, USA
Abbreviations and Acronyms CSF: Cerebrospinal fluid EE: Endoscopic, endonasal GTR: Gross total resection MS: Microsurgical
Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.024
-
To whom correspondence should be addressed: William T. Couldwell, M.D., Ph.D. [E-mail: [email protected]]
Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY -: e1-e7, - 2018
www.WORLDNEUROSURGERY.org
e1
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
METHODS Data Acquisition After receiving institutional board review approval, we undertook a retrospective cohort study of patients who underwent a MS transsphenoidal approach for resection of pituitary adenoma. All patients who underwent resection from February 14, 2002, to May 2, 2017, were identified. Subsequently, cases were narrowed to patients with ages 60 years. Patients with nonpituitary lesions or with inadequate data were excluded from analysis. Patients were divided into groups 1 through 3 depending on age: 60e70 (group 1), 71e80 (group 2), and >80 years (group 3). Demographic and surgical characteristics were reviewed, including patient age, sex, and body mass index, symptoms prompting surgical presentation, tumor type, tumor size, previous pituitary tumor resection, pre- and postoperative hormone use, tumor recurrence, length of follow-up, use of endoscope, fat/fascia use, CSF diversion (e.g., multiple lumbar punctures or lumbar drain), surgery date, operative time (as determined from stated in and out room times), and estimated blood loss. Complications were reviewed, including all unanticipated intraoperative and postoperative events. Hormone supplementation pre- or postoperatively regardless of duration was noted. Gross total resection (GTR) was defined as the removal of all visible tumor on T1weighted contrast-enhanced imaging. An endoscope is used in specific cases to ensure adequate tumor removal. Statistical Analysis Continuous variables were described as a mean standard deviation, whereas discrete variables were described as frequency (% of total). Continuous and discrete variables were analyzed via the t test and c2 test, respectively. A P value <0.05 was considered statistically significant. Data were analyzed using SPSS (version 20.0; IBM, Armonk, New York, USA).
macroadenomas, including 83.2% in group 1, 83.1% in group 2, and 80.0% in group 3 (P ¼ 0.5). GTR was achieved in a total of 67.2%, 56.9%, and 80.0% of adenomas in groups 1, 2, and 3, respectively (P ¼ 0.7). An overall GTR of 64.9% was seen for the elderly population. No differences in operative room time (P ¼ 0.1), estimated blood loss (P ¼ 0.8), endoscope use (P ¼ 0.7), fat/fascia use (P ¼ 0.4), or CSF diversion (P ¼ 0.1) were observed among groups. The preoperative hormone use rates of 29.8% in group 1, 29.2% in group 2, and 30.0% in group 3 did not differ (P ¼ 0.995), nor did the rates of postoperative hormone use (P ¼ 0.6). There was a significant increase in hormone use postoperatively in groups 1 (P ¼ 0.003) and 2 (P ¼ 0.05), but not group 3 (P ¼ 0.2) (c2 test). Patient complication rates also were similar regardless of patient age, with a rate of 6.1% in group 1, 9.2% in group 2, and 0.0% in group 3 patients (P ¼ 0.8). An overall complication rate of 6.8% was seen in the entire cohort. The mean length of follow-up (P ¼ 0.2) and tumor recurrence rate (P ¼ 0.8) were also similar in all patient age groups. DISCUSSION Study Findings The results of this study support the safety and efficacy of MS resection during the treatment of pituitary adenomas in elderly patients. Overall GTR rates of 56.9%e80% were seen in patients >60 years of age depending on age decile, without any statistically significant differences among the 3 groups (Table 1). No difference in operative room time or estimated blood loss was seen among elderly patients of different ages. The rate of patient complications ranged from 0% to 9.2%, which was statistically similar in all age deciles. There were no deaths associated with MS resection in this series. These findings indicate that age alone should not be exclusionary as age did not correlate with outcomes.
RESULTS A total of 634 patients who underwent MS resection for pituitary adenoma were retrospectively identified. For the purposes of this study, these were limited to 205 elderly patients, who were divided into 3 groups: between 60 and 70 years (n ¼ 131), 71e80 years (n ¼ 65), and >80 (n ¼ 9) (Table 1). The mean ages for groups 1, 2, and 3 were 65.2 3.2 years, 74.3 3.0 years, and 83.6 3.0 years, respectively (Table 1, Figure 1). The groups differed only in age. Most patients were male, including 53.4% of group 1, 69.2% of group 2, and 60.0% of group 3 patients (P ¼ 0.2). Patient body mass index was similar among groups (P ¼ 0.5). The most common presenting symptom was visual dysfunction, occurring in 56.5% of patients in group 1, 73.8% in group 2, and 50.0% in group 3. The next most common symptom was headache, including 33.6% of patients in group 1, 36.9% in group 2, and 20.0% in group 3. There was a greater incidence of incidental adenomas (30.0%) in group 3 patients compared with group 1 (14.5%) and group 2 (7.7%); however, there were no significant differences in overall symptomatology (P ¼ 0.2). Most tumors were nonfunctional adenomas, including 76.3% in group 1, 78.5% in group 2, and 90.0% in group 3 (P ¼ 0.97). In addition, most tumors were
e2
www.SCIENCEDIRECT.com
Modern Treatment of Pituitary Adenomas in Elderly Patients Multiple studies have evaluated the role of MS resection in elderly patients with pituitary adenoma (Table 2). Earlier studies suggested efficacy in tumor resection but significant rates of complications in elderly patients.6-10,27 However, later studies evaluating MS resection began showing improved efficacy and safety after MS resection in elderly patients.11,12,15,18 Hong et al.12 evaluated 103 patients aged 65 years and demonstrated GTR in 47.6% of cases. Complications included transient diabetes insipidus in 37.9%, CSF leaks in 4.9%, permanent visual dysfunction in 1.9%, and postoperative hypopituitarism in 10.7%. Sheehan et al.18 evaluated 64 patients 70 years and reported a mean length of stay of 2.6 days, with a 12.5% rate of new postoperative hormonal deficits and no surgery-related deaths. These more recent results are in line with our current findings showing GTR rates from 67.2% to 80% and complication rates from 0.0% to 9.2% (overall 6.8%). Moreover, although complications varied with age group in our study, the rates were not statistically significantly different. Thus, our results reflect high success rates in surgical GTR for most tumors regardless of age.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.024
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
Table 1. Demographic and Surgical Characteristics for Elderly Patients Undergoing Transsphenoidal Resections of Pituitary Adenomas Variable Age, years, mean SD
Group 1, 60e70 years, n [ 131
Group 2, 71e80 years, n [ 65
Group 3, >80 years, n [ 10
P Value
65.2 3.2
74.3 3.0
83.6 3.0
0.0001
Sex (males), % total
70 (53.4%)
45 (69.2%)
6 (60.0%)
0.2
Body mass index, kg/m2, mean SD
30.5 6.3
29.6 5.5
28.7 3.2
0.5
Symptoms, % total
0.2
Visual disturbance
74 (56.5%)
48 (73.8%)
5 (50.0%)
Incidental
19 (14.5%)
5 (7.7%)
3 (30.0%)
Apoplexy
14 (10.7%)
11 (16.9%)
1 (10.0%)
Endocrinopathy
29 (22.1%)
15 (23.1%)
1 (10.0%)
Headache
44 (33.6%)
24 (36.9%)
2 (20.0%)
5 (3.8%)
0 (0.0%)
1 (10.0%)
Failure of medical management Pituitary tumor type, % total Nonfunctional adenoma
0.97 100 (76.3%)
51 (78.5%)
9 (90.0%)
Prolactinoma
6 (4.6%)
2 (3.1%)
0 (0.0%)
Growth hormone
5 (3.8%)
3 (4.6%)
0 (0.0%)
Cortisol-secreting
2 (1.5%)
1 (1.5%)
0 (0.0%)
Other/atypical
7 (5.3%)
2 (3.1%)
1 (10.0%)
Unknown
11 (8.4%)
6 (9.2%)
0 (0.0%)
Microadenoma
13 (9.9%)
7 (10.8%)
1 (10.0%)
Macroadenoma
109 (83.2%)
54 (83.1%)
8 (80.0%)
Giant adenoma
2 (1.5%)
3 (4.6%)
1 (10.0%)
Unknown
7 (5.3%)
1 (1.5%)
0 (0.0%)
Endocrinologic normalization, % total
108 (82.4%)
48 (73.8%)
9 (90.0%)
0.5
Gross total resection, % total
88 (67.2%)
37 (56.9%)
8 (80.0%)
0.7
Tumor size, % total
Room time, hours, mean SD
0.5
3.2 0.9
3.3 0.9
2.6 0.7
0.1
121.4 253.7
136.9 178.8
73.6 59.5
0.8
Endoscope use, % total
9 (6.9%)
5 (7.7%)
0 (0.0%)
0.7
Fat/fascia use, % total
88 (67.2%)
49 (75.4%)
7 (70.0%)
0.4
Estimated blood loss, mL, mean SD
CSF diversion, % total None
0.1 112 (85.5%)
55 (84.6%)
7 (70.0%)
Lumbar puncture
8 (6.1%)
3 (4.6%)
3 (30.0%)
Lumbar drain
3 (2.3%)
4 (6.2%)
0 (0.0%)
8 (6.1%)
3 (4.6%)
0 (0.0%)
Any preoperative hormone use, % total
Unknown
39 (29.8%)
19 (29.2%)
3 (30.0%)
0.995
Any postoperative hormone use, % total
63 (48.1%)
30 (46.2%)
6 (60.0%)
0.6
3 (2.3%)
6 (9.2%)
0 (0.0%)
0.08
Return to OR, % total
Bold value indicates statistically significant. SD, standard deviation; CSF, cerebrospinal fluid; OR, operating room; ICA, internal carotid artery. *Two deaths were reported in this group at last follow-up but were not due to the transsphenoidal surgery.
WORLD NEUROSURGERY -: e1-e7, - 2018
Continues
www.WORLDNEUROSURGERY.org
e3
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
Table 1. Continued Variable Any complication, % total CSF leak
Group 1, 60e70 years, n [ 131
Group 2, 71e80 years, n [ 65
Group 3, >80 years, n [ 10
P Value
8 (6.1%)
6 (9.2%)
0 (0.0%)
0.8
3 (2.3%)
3 (4.6%)
0 (0.0%)
Meningitis
2 (1.5%)
0 (0.0%)
0 (0.0%)
Cranial hematoma
0 (0.0%)
1 (1.5%)
0 (0.0%)
ICA injury
1 (0.8%)
1 (1.5%)
0 (0.0%)
Postoperative epistaxis
2 (1.5%)
0 (0.0%)
0 (0.0%)
Death
0 (0.0%)*
0 (0.0%)
0 (0.0%)
0 (0.0%)
1 (1.5%)
0 (0.0%)
Follow-up, months, mean SD
Readmission within 30 days
28.3 33.5
22.7 30.2
8.9 9.1
0.2
Recurrence on follow-up, % total
6 (4.6%)
3 (4.6%)
0 (0.0%)
0.8
52.3 72.4
43.4 39.9
e
0.7
Time until recurrence, months, SD
Bold value indicates statistically significant. SD, standard deviation; CSF, cerebrospinal fluid; OR, operating room; ICA, internal carotid artery. *Two deaths were reported in this group at last follow-up but were not due to the transsphenoidal surgery.
Comparison of the MS and EE Approaches in Elderly Patients With the improved efficacy of the EE approach, a strong desire to compare MS and EE approaches in elderly patients has been seen specifically for pituitary adenomas as a possible way of improving safety and efficacy. Pereira et al.26 evaluated 102 patients 70 years who underwent MS (48.1%) or EE (51.9%) for pituitary adenoma resection. A total of 79% of patients had improved or stable endocrine function, and 91% showed improved or stable visual deficits. No difference in outcomes or complications was seen between patients who underwent MS compared with EE. Some studies have shown good safety with the EE approach in elderly patients,20 whereas others have shown greater complication rates, specifically perioperative medical
Figure 1. Distribution of patient age for the entire cohort of patients (A) and of elderly patients (60
e4
www.SCIENCEDIRECT.com
complications, in elderly patients.24 Gondim et al.23 evaluated 603 patients, with 493 <60 years of age and 110 60 years of age who underwent EE resection. GTR rates of 76.6% in patients 60e69 years and 78.2% in patients 70e84 years of age were observed. Overall complication rates were 20.0% and 32.7% in patients age 60e69 years or 70e84 years, respectively, which were significantly greater than the 10.0% overall complication rate in patients <60 years of age (P < 0.05). These results suggest that an EE approach would not simply be more efficacious in the elderly population compared with a MS approach. In addition, the use of the EE approach in our own experience is associated with longer operative and anesthetic times (W.T. Couldwell, unpublished data).
years) (B) treated with transsphenoidal approaches for pituitary adenoma resection.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.024
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
Table 2. Summary of Studies of Transsphenoidal Surgery in Elderly Patients Reference
Age Cutoff, years
Sample Size
Gross Total Resection Rate
Complication Rate
Puchner et al., 19956
65
15
100%*
0.0%
7
Benbow et al., 1997
65
44
Fraioli et al., 19998
70
11
65
84
10
Kurosaki et al., 2000
70
32
Kurosaki et al., 200127
80
15
Ferrante et al., 200211
70
39
Letournel et al., 200328
65
59
Del Monte et al., 200729
65
27
9
Turner et al., 1999
34.4% complication; 9.1% death 54.4%
0.0%
75.0%
0.0%
0.0%
29.6%
70
64
Hong et al., 200812
65
103
68.9%
Locatelli et al., 201315
65
43
54%
Yunoue et al., 201419
80
10
26
70
102
79.0%
1.9% hypotension; 2.9% transfusion; 9.6% transient DI; 8.7% SIADH; 0.9% CSF leak; 0% death
65
38
61.0%
0.0%
70
55
68.7%
9% CSF leak; 3.6% permanent DI; 7.2% hypertension; 1.8% myocardial ischemia; 1.8% death
65
25
Zhan et al., 2015
65
158
75.9%
Transient DI 17.8%; permanent DI 4.4%; CSF leak 6.4%
Liu et al., 201514
65
158
Zhao et al., 2017
65
130
Fujimoto et al., 201722
80
12
80
15
53.3% 65 years; 73.5% 80 years
0.0%
Wilson et al., 2018
70
54
70.4%
7.4% 60e69 years; 18.5% 70 years
Sasagawa et al., 201817
65
24
67.0%
17.0%
Sheehan et al., 2008
18
Pereira et al., 2014
Robenshtok et al., 201416 Gondim et al., 2015
23
Marenco et al., 201530 25
20
21
Chinezu et al., 2017
24
0.0%
0.0% 0.0%
4.3%
25.0% CSF leak
DI, diabetes insipidus; SIADH, syndrome of inappropriate antidiuretic hormone secretion; CSF, cerebrospinal fluid. *Normalization of growth hormone levels (<4.5 mg/L) for all patients seen.
Nuances of Pituitary Adenomas in Elderly Patients Management of pituitary tumors in elderly patients is further complicated by nuances of neurosurgical management and medical comorbidities.31-37 Kinoshita et al.13 performed a meta-analysis of 32 studies from 2000 to 2018 containing the key words “pituitary adenoma” and “elder” OR “elderly.” The definition of “elderly” varied from 65 years of age to 80 years of age. Elderly patients commonly presented with nonfunctional tumors but also showed tumor sizes that were similar to those of younger patients reported in the literature. Greater rates of ophthalmoplegia from mass effect in elderly patients were reported compared with younger patients. Increased numbers of comorbid conditions, greater American Society of Anesthesia physical status classification grade, and greater Charlson comorbidity index were reported. Perioperative mortality was low but did increase in some studies with older age groups. Patient morbidity, specifically
WORLD NEUROSURGERY -: e1-e7, - 2018
postoperative hematoma, CSF leak, postoperative hyponatremia, and hormone dysfunction, also increased in older ages. Tumor recurrence was less likely in elderly patients compared with younger patients. Tumor resection rates were similar, with a range of 71%e100% of patients showing improvement of visual symptoms. Our study also supports these findings, showing that modern MS resection can be safe and effective. We did not, however, find worse outcomes in older patients. Visual disturbances as a primary presenting feature of pituitary adenomas in elderly patients often can be misleading and result in delay of diagnosis if elderly patients are worked up for other ophthalmologic issues (e.g., glaucoma, macular degeneration, cataracts). Similarly, the increased rate of pre- and postoperative hormonal dysfunction suggests that greater attention to evaluation and supplementation is required in the elderly population. Overall, the diagnosis of pituitary
www.WORLDNEUROSURGERY.org
e5
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
adenomas in elderly patients seems to require a high index of suspicion while the operative treatment involves recognition of perioperative comorbidities.
been previously reported by our group38,39 and was not the focus of this specific study. CONCLUSIONS
Limitations This is a single-center study, performed by an experienced single neurosurgeon; thus, one limitation may be in the generalizability of these findings to other centers. No EE cohort was used for comparison. Similarly, we did not assess postoperative clinical outcome by standardized visual field examination or quality-of-life measures, which makes evaluation of surgical efficacy difficult. Finally, this is a retrospective cohort study, where safety and efficacy may be biased by patient selection and inclusion. We did not specifically compare a patient cohort <60 years since this has
REFERENCES 1. Moncef B, Pierre K. Brain and Spine Surgery in the Elderly. Cham, Switzerland: Springer International Publishing; 2017. 2. He W, Goodkind D, Kowal P. An Aging World: 2015. Washington, DC: U.S. Census Bureau, International Population Reports, P95/16e1; 2016. 3. Clegg A, Young J, Iliffe S, Rikkert MO, Rockwood K. Frailty in elderly people. Lancet. 2013;381:752-762. 4. Rockwood K, Song X, MacKnight C, et al. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005;173:489-495. 5. McDowell BD, Wallace RB, Carnahan RM, Chrischilles EA, Lynch CF, Schlechte JA. Demographic differences in incidence for pituitary adenoma. Pituitary. 2011;14:23-30.
The results of our study support the safety and efficacy of MS resection on pituitary adenomas in elderly patients. Age alone should not be an exclusionary criterion in the treatment of these patients. The selection of this approach, however, highly depends on patient-specific factors, attending preference, and institutional resources. ACKNOWLEDGMENTS We thank Kristin Kraus, MSc, for her editorial assistance.
transsphenoidal surgery and follow-up. J Clin Neurosci. 2008;15:1091-1095. 13. Kinoshita Y, Kurisu K, Arita K. Nonfunctioning pituitary adenomas in elderly patients. J Clin Neurosci. 2018;53:127-131. 14. Liu J, Li C, Xiao Q, et al. Comparison of pituitary adenomas in elderly and younger adults: clinical characteristics, surgical outcomes, and prognosis. J Am Geriatr Soc. 2015;63:1924-1930. 15. Locatelli M, Bertani G, Carrabba G, et al. The trans-sphenoidal resection of pituitary adenomas in elderly patients and surgical risk. Pituitary. 2013; 16:146-151. 16. Robenshtok E, Benbassat CA, Hirsch D, et al. Clinical course and outcome of nonfunctioning pituitary adenomas in the elderly compared with younger age groups. Endocr Pract. 2014;20:159-164.
6. Puchner MJ, Knappe UJ, Ludecke DK. Pituitary surgery in elderly patients with acromegaly. Neurosurgery. 1995;36:677-683 [discussion: 683684].
17. Sasagawa Y, Hayashi Y, Tachibana O, et al. Transsphenoidal surgery for elderly patients with acromegaly and its outcomes: comparison with younger patients. World Neurosurg. 2018;118: e229-e234.
7. Benbow SJ, Foy P, Jones B, Shaw D, MacFarlane IA. Pituitary tumours presenting in the elderly: management and outcome. Clin Endocrinol (Oxf). 1997;46:657-660.
18. Sheehan JM, Douds GL, Hill K, Farace E. Transsphenoidal surgery for pituitary adenoma in elderly patients. Acta Neurochir (Wien). 2008;150: 571-574 [discussion: 574].
8. Fraioli B, Pastore FS, Signoretti S, De Caro GM, Giuffre R. The surgical treatment of pituitary adenomas in the eighth decade. Surg Neurol. 1999;51: 261-266 [discussion: 266-267].
19. Yunoue S, Tokimura H, Tominaga A, et al. Transsphenoidal surgical treatment of pituitary adenomas in patients aged 80 years or older. Neurosurg Rev. 2014;37:269-276 [discussion: 276-277].
9. Turner HE, Adams CB, Wass JA. Pituitary tumours in the elderly: a 20 year experience. Eur J Endocrinol. 1999;140:383-389.
20. Zhao Y, Lian W, Xing B, et al. The clinical characteristics and microsurgical therapy of pituitary adenomas in elderly patients: a retrospective study of 130 cases. J Clin Neurosci. 2017;46:13-16.
10. Kurosaki M, Ludecke DK, Flitsch J, Saeger W. Surgical treatment of clinically nonsecreting pituitary adenomas in elderly patients. Neurosurgery. 2000;47:843-848 [discussion: 848-849]. 11. Ferrante L, Trillo G, Ramundo E, et al. Surgical treatment of pituitary tumors in the elderly: clinical outcome and long-term follow-up. J Neurooncol. 2002;60:185-191. 12. Hong J, Ding X, Lu Y. Clinical analysis of 103 elderly patients with pituitary adenomas:
e6
www.SCIENCEDIRECT.com
21. Chinezu R, Fomekong F, Lasolle H, et al. Risks and benefits of endoscopic transsphenoidal surgery for nonfunctioning pituitary adenomas in patients of the ninth decade. World Neurosurg. 2017; 106:315-321. 22. Fujimoto K, Yano S, Shinojima N, Hide T, Kuratsu JI. Endoscopic endonasal transsphenoidal surgery for patients aged over 80 years with pituitary adenomas: surgical and follow-up results. Surg Neurol Int. 2017;8:213.
23. Gondim JA, Almeida JP, de Albuquerque LA, Gomes E, Schops M, Mota JI. Endoscopic endonasal transsphenoidal surgery in elderly patients with pituitary adenomas. J Neurosurg. 2015;123: 31-38. 24. Wilson PJ, Omay SB, Kacker A, Anand VK, Schwartz TH. Endonasal endoscopic pituitary surgery in the elderly. J Neurosurg. 2018;128: 429-436. 25. Zhan R, Ma Z, Wang D, Li X. Pure endoscopic endonasal transsphenoidal approach for nonfunctioning pituitary adenomas in the elderly: surgical outcomes and complications in 158 patients. World Neurosurg. 2015;84:1572-1578. 26. Pereira EA, Plaha P, Chari A, et al. Transsphenoidal pituitary surgery in the elderly is safe and effective. Br J Neurosurg. 2014;28:616-621. 27. Kurosaki M, Saeger W, Ludecke DK. Pituitary tumors in the elderly. Pathol Res Pract. 2001;197: 493-497. 28. Letournel F, Menei P, Guy G, Saint-Andre JP. Transsphenoidal surgery in the elderly. J Am Geriatr Soc. 2003;51:729-730. 29. Del Monte P, Foppiani L, Ruelle A, et al. Clinically non-functioning pituitary macroadenomas in the elderly. Aging Clin Exp Res. 2007;19:34-40. 30. Marenco HA, Zymberg ST, Santos Rde P, Ramalho CO. Surgical treatment of non-functioning pituitary macroadenomas by the endoscopic endonasal approach in the elderly. Arq Neuropsiquiatr. 2015;73:764-769. 31. Taussky P, Kalra R, Coppens J, Mohebali J, Jensen R, Couldwell WT. Endocrinological outcome after pituitary transposition (hypophysopexy) and adjuvant radiotherapy for tumors involving the cavernous sinus. J Neurosurg. 2011; 115:55-62. 32. Liu JK, Weiss MH, Couldwell WT. Surgical approaches to pituitary tumors. Neurosurg Clin N Am. 2003;14:93-107. 33. Liu JK, Orlandi RR, Apfelbaum RI, Couldwell WT. Novel closure technique for the endonasal transsphenoidal approach. Technical note. J Neurosurg. 2004;100:161-164.
WORLD NEUROSURGERY, https://doi.org/10.1016/j.wneu.2018.11.024
ORIGINAL ARTICLE MOHAMMED A. AZAB ET AL.
PITUITARY ADENOMA RESECTION IN ELDERLY PATIENTS
34. Hornyak M, Couldwell WT. Multimodality treatment for invasive pituitary adenomas. Postgrad Med. 2009;121:168-176. 35. Couldwell WT, Weiss MH, Rabb C, Liu JK, Apfelbaum RI, Fukushima T. Variations on the standard transsphenoidal approach to the sellar region, with emphasis on the extended approaches and parasellar approaches: surgical experience in 105 cases. Neurosurgery. 2004;55:539-547 [discussion: 547550].
prolactinomas. Neurosurg Clin N Am. 2003;14: 89-92. vii.
outcomes after transsphenoidal resection of sellar tumors. Neurosurgery. 2018;83:726-731.
37. Couldwell WT. Transsphenoidal and transcranial surgery for pituitary adenomas. J Neurooncol. 2004; 69:237-256.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
38. Karsy M, Bowers CA, Scoville J, et al. Evaluation of complications and costs during overlapping transsphenoidal surgery in the treatment of pituitary adenoma [E-pub ahead of print]. Neurosurgery. https://doi.org/10.1093/ neuros/nyy269, Accessed August 9, 2018.
Received 24 August 2018; accepted 4 November 2018 Citation: World Neurosurg. (2018). https://doi.org/10.1016/j.wneu.2018.11.024 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com
36. Couldwell WT, Rovit RL, Weiss MH. Role of surgery in the treatment of micro-
39. Guan J, Karsy M, Bisson EF, Couldwell WT. Patient-level factors influencing of hospital costs and short-term patient-reported
WORLD NEUROSURGERY -: e1-e7, - 2018
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
www.WORLDNEUROSURGERY.org
e7