J Korean Soc Geriatr Neurosurg > Volume 20(1); 2024 > Article
Nam, Byun, Kim, Kim, Park, and Kim: Surgical indications and outcomes of the endoscopic endonasal approach for brain tumors in older adults in Korea: a retrospective study

Abstract

Objective

This study explored the surgical indications for pituitary adenomas (PAs) in older patients by analyzing the outcomes of the transsphenoidal approach (TSA).

Methods

We retrospectively analyzed patients aged 65 years or older who underwent TSA from March 2020 to October 2023. We evaluated the preoperative and postoperative neurological and endocrinological features, degree of tumor resection, and perioperative complications.

Results

In total, 134 patients aged 65 years or older (20.5%; 70 men and 64 women) underwent TSA (70-74 years: 48 patients, 75-79 years: 14 patients, ≥80 years: 8 patients). Among the 102 PAs, nonfunctioning PAs (NF-PAs) were the most common subtype (n=96, 94.1%), and overall gross total resection was achieved in 89 (87.3%) patients. Intraoperative cerebrospinal fluid (CSF) leakage occurred in 32 of 102 patients with PAs; however, none of those patients experienced postoperative CSF leakage. In the NF-PA group, endocrinological function improved in 11 (12.6%) patients and worsened in four (4.6%). Preoperative visual field defects were present in 71 (74.6%) patients; 48 (67.6%) of them improved, and 5 (7.0%) worsened. Meningiomas were grossly resected in four of the eight patients, and four of the six patients with visual field defects experienced improvement. One patient had postoperative CSF leakage. Craniopharyngiomas were resected in six of eight patients, including two with recurrent tumors.

Conclusion

TSA was safe in patients older than 65 years. However, unpredictable adverse effects could occur. Judicious decisions regarding surgical indications based on the natural history of the tumor subtypes and life expectancy are essential.

Introduction

In Korea, tumors of the sellar region account for 21.1% of brain tumors, making them the third most common, and the incidence of pituitary adenoma (PA) is 5.8 cases per 100,000 people [1,2]. Similarly to the trends observed in the United States, the overall incidence of nonmalignant tumors is gradually increasing in Korea; consequently, the importance of tumors in the sellar region, including PA, is on the rise [1-3]. Reports from societies already experiencing an aging society showed that the incidence of these tumors is notably greater in elderly patients, with the peak incidence reported in the 60s [3-6]. According to Statistics Korea, up to 18.5% of the Korean population are aged 65 years and older in 2023, and this population is expected to further increase to 20.6% by 2025, entering the ultraelderly society. Life expectancy is also on the rise, with an expected lifespan of 21.6 years at the age of 65 and 13.4 years at the age of 75 years, based on 2021 estimates [7]. The transsphenoidal approach (TSA) has been used in the elderly population worldwide, but its feasibility and complications have been discussed [8-16]. This study was conducted to investigate the safety and effectiveness of TSA in the elderly population.

Material and Method

We obtained a cohort of patients who underwent surgery via the TSA at our institution between March 2020 and October 2023. Among a total of 654 patients who underwent TSA, 134 patients aged 65 and older were identified. Preoperative neuro-endocrinological status, intraoperative features, and surgical outcomes were retrospectively obtained through the review of medical records. All patients underwent preoperative endocrinological, ophthalmological, rhinological, and neurologic evaluations as well as follow-up evaluations performed 3 months after surgery, as described in our previous report. The surgical procedures were described in detail in our previous report [17,18]. Briefly, extracapsular dissection was adopted for PAs employing a pseudocapsule, while other tumors were removed via the microdissection technique with extraarachnoid dissection from neurovascular structures. In patients where tumors invaded the cavernous sinus, the medial wall of the cavernous sinus was removed. Reconstruction using a nasoseptal flap was performed for grade 3 intraoperative cerebrospinal fluid (CSF) leakage [19]. Nasal cavity examinations were conducted 2 days, 1 week, and 2 or 4 weeks after surgery. Elastic stockings were used to prevent deep vein thrombosis (DVT) and pulmonary thromboembolism (PTE) during the first week after surgery, and active ambulation was encouraged immediately after surgery. To prevent postoperative hyponatremia in patients with PAs, oral water intake was restricted daily from postoperative days 5 to 10.
All the statistical analyses were performed and graphs were generated using the open-source software Python ver. 3.11.5.

Results

The basic demographic characteristics are shown in Table 1. There was no significant difference in the sex distribution (70 males, 64 females; P=0.4). The age distribution in the elderly group was shown in Fig. 1. The elderly population had a significantly higher proportion of pituitary adenomas (PAs) compared to the younger population (P=0.001), and the proportions of all tumors between age groups are shown in Fig. 2. The proportion of functioning PAs in the elderly population was significantly lower than that in the other population; there was only one case of Cushing disease, 3 cases of acromegaly, and 2 cases of thyroid-stimulating hormone adenoma (P<0.001). In PAs, the transtuberculum approach was performed in 9 patients (8.8%). The surgical outcomes of the PAs are described in Table 2. Gross total resection (GTR) was achieved in 87.3% of PAs, 50% of meningiomas, 75% of craniopharyngiomas, and 33% of chondrosarcomas. There was one mortality (0.7%) in a patient with recurrent craniopharyngioma.
Intraoperative CSF leakage occurred in 32 PAs. Reconstruction with multilayer fibrin sealants was performed in 7 patients, multilayer fibrin sealants with pedicled nasoseptal flaps were used in 9 patients, and multiple on-lay reconstructions were used in 16 patients, resulting in no postoperative CSF leakage. In 8 meningioma patients, postoperative CSF leakage occurred in one patient, and a shallow crack along the optic canal was identified during the revision surgery. Postoperative meningitis occurred in 8 out of the total 132 patients (6.0%).
Endocrinologic and visual outcomes for nonfunctioning PA (NF-PA) patients are shown in Table 3. Regarding visual outcomes in detail, for NF-PA patients, visual field data were unavailable for 7 patients. Among the 71 patients with preoperative visual disturbance, vision improved in 48 (70.6%), did not change in 15 (22.1%) and deteriorated in 5 (7.4%). Postoperative visual field analysis was unavailable 3. All four patients presented with preoperative diplopia, which was normalized. Four out of the 6 meningioma patients with visual disturbances showed improvement, and all 3 Rathke's cleft cyst patients with visual symptoms improved. None of the patients without preoperative visual disturbance experienced deterioration in any kind of tumor.
Among the 87 patients with NF-PAs and preoperative endocrinologic deficiency, 11 (12.6%) experienced improvement, 72 (82.8%) experienced stable disease, and 4 (4.6%) experienced worsening. Endocrinological remission was achieved in all patients with functioning PAs (n=6).
All general medical complications among the elderly were delineated by age group at 5-year intervals, as presented in Table 4. Postoperatively, excluding craniopharyngioma patients, transient diabetes insipidus occurred in 27 patients (21.4%), persisting in 5 patients (4.0%). Hyponatremia within 1 month occurred in 23 patients (17.2%). Other postoperative general complications included pneumonia in one patient (0.7%) and delirium in 6 patients (4.5%). No patients suffered from DVT or PTE. There were no significant differences between age group at 5-year intervals.

Discussion

TSA in elderly patients requires careful consideration of surgical indications based on the natural history of the pathology, and tailored surgical techniques are required for identifying features of tissue with age-related changes. Additionally, preoperative evaluation and postoperative management should be implemented to minimize perioperative complications. Considering surgical intervention for elderly patients, it is important to take into account various factors, including life expectancy, tumor growth rate, and the potential for new neuroendocrine deterioration to develop. While clear guidelines and indications have not yet been established, surgery is recommended for improving visual and hormonal symptoms in the general population (class II evidence) [20,21]. In patients with Cushing disease, surgical resection is essential regardless of age due to the life-threatening complications associated with hypercortisolism, such as infection and thromboembolism [22,23]. In certain instances, acromegaly may manifest at advanced ages, while in others, symptoms may have been present for a long time before the diagnosis was made. In the latter case, regular evaluation is performed if there are no complications caused by the hypersecretion of growth hormones, such as cardiovascular health, the development of malignancies, diabetes mellitus, or dyslipidemia, because acromegaly does not pose a risk of decreased life expectancy [24]. Despite concerns about the increased risk of perioperative complications due to general comorbidities in elderly patients, surgery remains the primary recommendation for improving outcomes, just as for younger patients [2,23-25]. For NF-PAs, previous reports have shown that macroadenomas can increase tumor volume and may lead to symptoms such as visual disturbance, pituitary apoplexy, and endocrine dysfunction [26,27]. Therefore, surgical decisions should be based on predicting life expectancy and the likelihood of symptom development in elderly patients [10-16,21,26,28,29]. Endocrinological status changes with age in elderly patients. Testosterone levels in men peak and gradually decline from the 20 s to 8 decades of age and rapidly decline thereafter, while in women, testosterone levels begin to rise in adolescence and remain steady as the concentration of sex hormone binding protein continues to increase [30]. Dehydroepiandrosterone, growth hormone, and insulin-like growth factor-1 also decrease with age [31,32]. Recognizing the natural changes in hormones and distinguishing them from preoperative endocrinological deficiencies while considering the potential for postoperative recovery are crucial for determining surgical indications [13,29]. Reports suggest that hormonal recovery is not related to age, and the results of this study showed a 12.6% recovery rate, consistent with previous findings [12,17].
Moreover, visual disturbance in elderly patients requires additional considerations, such as increasing lens opacity with age, which can lead to a greater incidence of cataract surgery [12,14,33]. Previous reports have shown that the recovery of visual impairment scores was not different between older patients and younger patients, but the degree of improvement was different. Interestingly, although visual impairment scores were not obtained in this study, 70.6% of patients’ vision appeared to improve, which is not dissimilar from what was previously reported [13,14].
In terms of tumor control, the GTR rate for elderly patients (16.7%-76.8%) did not significantly differ from that for younger patients, similar to the findings of this study (87.3% for PAs, 80.0% overall) [10-15,29]. Although not statistically significant, a previous study showed a trend toward slightly lower recurrence rates in the elderly population [13].
Surgical complications such as CSF leakage and infections, including meningitis, did not significantly differ between elderly and younger patient groups. In this study, the reported CSF leakage incidence (0.7%) was not notably greater than that in previous studies (mean, 6.3; range, 0-7) [13]. Stepwise reconstruction methods based on the extent of leakage are crucial for preventing major complications related to CSF leakage [19,34,35].
There are generally more perioperative complications in elderly patients than in younger patients, and they require more time to recover [36,37]. However, age itself is not the most important factor for predicting postoperative morbidity and mortality. Instead, preoperative functional status and medical comorbidities play a more critical role in predicting postoperative outcomes, emphasizing the need for careful assessment of functional status rather than relying solely on age, sex, or diagnosis to estimate surgical feasibility [36-39]. For PAs, a recent meta-analysis indicated a significantly greater rate of complications in patients aged 70 and above than in those aged younger than 70 years [13]. In particular, endocrine complications such as hyponatremia and diabetes insipidus are more common in elderly individuals [10,15]. Although not statistically significant in our series, both hyponatremia and diabetes insipidus were observed commonly in patients aged 70 and above. The association between electrolyte imbalance and postoperative medical complications highlights the importance of postoperative care in the management of complications in elderly people [15].
This study is essentially limited by the small surgical cohort. This was also a retrospective study, and statistical analysis was not performed by randomly assigning patients to cohorts or control groups. In addition, long-term follow-up data were not available, limiting the ability to evaluate long-term tumor recurrence.

Conclusion

There is concern that the benefit-risk ratio of TSA may decline with increasing age, but with proper surgical indication and postoperative management, tumor control and symptom improvement can be achieved with satisfactory results.

NOTES

No potential conflict of interest relevant to this article was reported.

Acknowledgments

This work was supported by the grant to Yong Hwy Kim from the New Faculty Startup Fund from Seoul National University (No. 800-20220266) and Seoul National University Hospital Research Fund (No. 0520200030).

Fig. 1.
Distribution of patients divided by age (5-year intervals).
jksgn-2024-00038f1.jpg
Fig. 2.
(A) Distribution of diagnoses in older patients who underwent transsphenoidal surgery among the overall population. (B) Distribution of diagnoses in older patients who underwent transsphenoidal surgery.
jksgn-2024-00038f2.jpg
Table 1.
Demographic characteristics of patients who underwent transsphenoidal surgery from March 2020 to October 2023
Characteristic Overall Age <65 yr (n, %) Age ≥65 yr (n, %) P-value
Total patients 654 520 (79.5) 134 (20.5)
Mean age (yr) 47.6 41.7 70.5
Sex (male:female) 318:336 248:272 70:64 0.4
Diagnosis
 Pituitary adenoma 418 316 (75.6) 102 (24.4) 0.001
 Nonfunctioning 310 214 96 <0.001
 Functioning 108 102 6
 Meningioma 51 43 (84.3) 8 (15.7) 0.73
 Craniopharyngioma 79 71 (89.9) 8 (10.1) 0.008 
 Rathkes cleft cyst 30 25 (83.3) 5 (16.7) 0.47
 Chordoma/chondrosarcoma 14 11 (78.6) 3 (21.4) 1.00
 Miscellaneous 62 54 (87.1) 8 (12.9) 0.036
Table 2.
Surgical outcomes of 102 older patients with pituitary adenomas
Outcome Degree n (%)
Removal extent Gross total removal 89 (87.3)
Subtotal removal 13 (12.7)
Intraoperative CSF leakage 32 (31.4)
Reconstruction Multilayer fibrin sealant 7 (21.9)
Multilayer fibrin sealant with flap 9 (28.1)
Multiple on-lay reconstruction 16 (50.0)
Postoperative CSF leakage 0 (0)
Postoperative meningitis 5 (4.9)

CSF, cerebrospinal fluid.

Table 3.
Endocrinological and visual outcomes in 96 nonfunctioning pituitary adenomas
Preoperative status n (%) Postoperative changes n (%)
Endocrinological status
 Normal 9 (9.4) No change 8 (88.9)
Deteriorated 1 (11.1)
 Insufficient 87 (90.6) Improved 11 (12.6)
No change 72 (82.8)
Deteriorated 4 (4.6)
Vision 
 Normal 24 (25.3) No change 21 (87.5) 
Deteriorated 0 (0)
 Defective 71 (74.7) Improved 48 (70.6)
No change 15 (22.1)
Deteriorated 5 (7.4)
Table 4.
General medical complications of 134 older patients by 5-year age groups
Complication Age group (yr) P-value
All those aged ≥65 65-69 70-74 75-79 ≥80
Total 134 64 48 14 8
DI 45 25 (39.1) 15 (31.3) 4 (28.6) 1 (12.5) 0.435
Hyponatremia 23 8 (12.5) 12 (25.0) 2 (14.3) 1 (12.5) 0.370
DVT and PE 0 0 (0) 0 (0) 0 (0) 0 (0)
Pneumonia 1 0 (0) 0 (0) 1 (7.1) 0 (0) 0.165
Infection 8 6 (9.4) 2 (4.2) 0 (0) 0 (0) 0.389
Delirium 6 4 (6.3) 0 (0) 2 (14.3) 0 (0) 0.103

Values are presented as number (%).

DI, diabetes insipidus; DVT, deep vein thrombosis; PE, pulmonary embolism.

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