Giant pituitary adenoma

Giant pituitary adenoma

Epidemiology

Giant pituitary adenomas comprise about 6-10% of all pituitary tumors.

It is estimated that 5% of pituitary adenoma become invasive and may grow to gigantic sizes (>4 cm in diameter).

They are mostly clinically non-functioning adenomas and occur predominantly in males 1)

Types

Clinical

The presenting symptoms are usually secondary to compression of neighboring structures, but also due to partial or total hypopituitarismFunctioning pituitary adenomas give rise to specific symptoms of hormonal hypersecretion.

Treatment

The use of dopamine agonists is considered a first-line treatment in patients with giant macroprolactinomas. Somatostatin analogs can also be used as primary treatment in cases of growth hormone and thyrotropin producing giant adenomas, although remission of the disease is not achieved in the vast majority of these patients.

The intrinsic complexity of these tumors requires the use of different therapies in a combined or sequential way. A multimodal approach and a therapeutic strategy involving a multidisciplinary team of expert professionals form the basis of the therapeutic success in these patients 2).


The main goal of surgical treatment of giant pituitary adenoma is maximum possible tumor extirpation with minimal side effects, which can be achieved by careful preoperative planning of operative approach, based on directions of tumor extensions and invasiveness. Maximal surgical removal of giant adenomas offers best chances to control tumor growth when followed with adjuvant medical and radiation therapies 3).


While the use of endoscopic approaches has become increasingly accepted in the resection of pituitary adenomas, limited evidence exists regarding the success of this technique for patients with large and giant pituitary adenomas.

Major blood supply of giant pituitary adenomas originates from branches of the infraclinoidal portion of the internal carotid artery, different from normal anterior pituitary gland. Surgical route should depend not only on tumor shape and extension but on feeding systems 4).

The main goal of surgical treatment of giant pituitary adenoma is maximum possible tumor extirpation with minimal side effects, which can be achieved by careful preoperative planning of operative approach, based on directions of tumor extensions and invasiveness. Maximal surgical removal of giant adenomas offers best chances to control tumor growth when followed with adjuvant medical and radiation therapies 5).


In cases of progressive enlargement of residual lesions, a second endoscopic debulking of the tumor may be considered for control of the disease 6).

Outcome

Giant pituitary adenomas carry higher surgical risks despite recent advances in microsurgical and/or endoscopic surgery, and postoperative acute catastrophic changes without major vessel disturbance are still extremely difficult to predict, may manifest as postoperative pituitary apoplexy, and are associated with very poor outcomes.

Resection of both large and giant pituitary adenomas by microscopic transsphenoidal surgery may be safe and effective surgical technique with low morbidity and mortality 7).

Case series

References

1) , 2)

Iglesias P, Rodríguez Berrocal V, Díez JJ. Giant pituitary adenoma: histological types, clinical features and therapeutic approaches. Endocrine. 2018 Sep;61(3):407-421. doi: 10.1007/s12020-018-1645-x. Epub 2018 Jun 16. Review. PubMed PMID: 29909598.
3)

Sinha S, Sharma BS. Giant pituitary adenomas–an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients. Br J Neurosurg. 2010 Feb;24(1):31-9. doi: 10.3109/02688690903370305. PubMed PMID: 20158350.
4)

Ogawa Y, Sato K, Matsumoto Y, Tominaga T. Evaluation of Fine Feeding System and Angioarchitecture of Giant Pituitary Adenoma – Implications for Establishment of Surgical Strategy. World Neurosurg. 2015 Oct 5. pii: S1878-8750(15)01255-3. doi: 10.1016/j.wneu.2015.09.087. [Epub ahead of print] PubMed PMID: 26455764.
5)

Sinha S, Sharma BS. Giant pituitary adenomas–an enigma revisited. Microsurgical treatment strategies and outcome in a series of 250 patients. Br J Neurosurg. 2010 Feb;24(1):31-9. doi: 10.3109/02688690903370305. PubMed PMID: 20158350.
6)

Gondim JA, Almeida JP, Albuquerque LA, Gomes EF, Schops M. Giant pituitary adenomas: surgical outcomes of 50 cases operated on by the endonasal endoscopic approach. World Neurosurg. 2014 Jul-Aug;82(1-2):e281-90. doi: 10.1016/j.wneu.2013.08.028. Epub 2013 Aug 29. PubMed PMID: 23994073.
7)

Karki M, Sun J, Yadav CP, Zhao B. Large and giant pituitary adenoma resection by microscopic trans-sphenoidal surgery: Surgical outcomes and complications in 123 consecutive patients. J Clin Neurosci. 2017 Aug 1. pii: S0967-5868(16)30922-5. doi: 10.1016/j.jocn.2017.07.015. [Epub ahead of print] PubMed PMID: 28778803.

Radiation necrosis treatment

Radiation necrosis treatment

Radiation necrosis (RN) will be increasingly encountered due to the widespread use of SRS. Symptomatic RN can cause significant morbidity and should be managed pro-actively. There is no single modality which can reliably distinguish RN from recurrent tumor, and a multi-modal approach is often required. For patients with symptomatic RN, oral corticosteroid therapy and bevacizumab are both effective. A minority of patients, with an unclear diagnosis, or refractory symptoms, will require surgical resection. As RN proves to be a challenging condition to diagnose and manage, risk factor mitigation becomes important in clinical decision making 1).


Using the internal database for pharmaceutical products, all patients who received BEV in the University of Munich were identified. Only patients who received BEV as symptomatic treatment for radiation necrosis were included. Patient characteristics, symptoms before, during, and after treatment, and the use of dexamethasone were evaluated using medical reports and systematic internal documentation. The symptoms were graded using CTCAE version 5.0 for general neurological symptoms. Symptoms were graded directly before each cycle and after the treatment (approximately 6 weeks). Additionally, the daily steroid dose was collected at these timepoints. Patients who either improved in symptoms, received less dexamethasone after treatment, or both were considered to have a benefit from the treatment.

Twenty-one patients who received BEV due to radiation necrosis were identified. For 10 patients (47.6%) symptoms improved and 11 patients (52.4%) remained clinically stable during the treatment. In 14 patients (66.7%) the dexamethasone dose could be reduced during therapy, 5 patients (23.8%) received the same dose of dexamethasone before and after the treatment, and 2 patients (9.5%) received a higher dose at the end of the treatment. According to this analysis, overall, 19 patients (90.5%) benefited from the treatment with BEV. No severe adverse effects were reported.

BEV might be an effective and safe therapeutic option for patients with radiation necrosis as a complication after cranial radiation therapy. Patients seem to benefit from this treatment by improving symptomatically or through reduction of dexamethasone 2).


Perez-Torres et al. validated the VEGF specificity by comparing the therapeutic efficacy of anti-VEGF with non-specific isotype control antibody. Additionally, they found that VEGF over-expression and radionecrosis developed simultaneously, which precludes preventative anti-VEGF treatment 3).

References

1)

Vellayappan B, Tan CL, Yong C, Khor LK, Koh WY, Yeo TT, Detsky J, Lo S, Sahgal A. Diagnosis and Management of Radiation Necrosis in Patients With Brain Metastases. Front Oncol. 2018 Sep 28;8:395. doi: 10.3389/fonc.2018.00395. eCollection 2018. Review. PubMed PMID: 30324090; PubMed Central PMCID: PMC6172328.
2)

Bodensohn R, Hadi I, Fleischmann DF, Corradini S, Thon N, Rauch J, Belka C, Niyazi M. Bevacizumab as a treatment option for radiation necrosis after cranial radiation therapy: a retrospective monocentric analysis. Strahlenther Onkol. 2019 Oct 4. doi: 10.1007/s00066-019-01521-x. [Epub ahead of print] PubMed PMID: 31586230.
3)

Perez-Torres CJ, Yuan L, Schmidt RE, Rich KM, Drzymala RE, Hallahan DE, Ackerman JJ, Garbow JR. Specificity of vascular endothelial growth factor treatment for radiation necrosis. Radiother Oncol. 2015 Sep 12. pii: S0167-8140(15)00462-4. doi: 10.1016/j.radonc.2015.09.004. [Epub ahead of print] PubMed PMID: 26376163.

Gamma Knife radiosurgery for trigeminal neuralgia

Gamma Knife radiosurgery for trigeminal neuralgia

Gamma knife radiosurgery (GKRS) is one of the alternatives for treatment for classical trigeminal neuralgia (TN).

The first use of SRS by Lars Leksell was for the treatment of trigeminal neuralgia. Initially, this was reserved for refractory cases following multiple operations 1).

The Leksell Gamma Knife and the Accuray CyberKnife systems have been used in the radiosurgical treatment of trigeminal neuralgia. The 2 techniques use different delivery methods and different treatment parameters. In the past, CyberKnife treatments have been associated with an increased incidence of treatment-related complications, such as facial numbness.

CyberKnife radiosurgical parameters can be optimized to mimic the dose distribution of Gamma Knife plans. However, Gamma Knife plans result in superior sparing of critical structures (brainstem, temporal lobe,and cranial nerves VII and VIII) and in steeper dose fall off away from the target. The clinical significance of these effects is unknown 2).

Indications

Generally recommended for patients with co-morbidities, high-risk medical illness, pain refractory to prior surgical procedures, or those on anticoagulants (anticoagulation does not have to be reversed to have SRS).

Mechanism

Treatment plan

4 -5 mm isocenter in the trigeminal nerve root entry zone identified on MRI. Use 70–80 Gy at the center, keeping the 80% isodose curve outside of the brainstem.

Results: Significant pain reduction after initial SRS: 80–96% 3) 4) 5) 6) but only ≈ 65% become pain free. Median latency to pain relief: 3 months (range: 1 d-13 months) 7).

Recurrent pain occurs with in three years in 10–25%. Patients with TN and multiple sclerosis are less likely to respond to SRS than those without MS. SRS can be repeated, but only after four months following the original procedure.

Outcome

Repeat Radiosurgery for Trigeminal Neuralgia

Case series

A total of 263 patients contributed by 9 member tertiary referral Gamma Knife centers (2 in Canada and 7 in USA) of the International Gamma Knife Research Consortium (IGKRF) constituted this study.

The median latency period of Facial pain response (PR) after SRS was 1 mo. Reasonable pain control (Barrow Neurological Institute Pain Scale I-IIIb) was achieved in 232 patients (88.2%). The median maintenance period from SRS was 14.1 months (range, 10 days to 10 years). The actuarial reasonable pain control maintenance rates at 1 yr, 2 yr, and 4 yr were 54%, 35%, and 24%, respectively. There was a correlation between the status of achieving BNI-I and the maintenance of facial pain recurrence-free rate. The median recurrence-free rate was 36 mo and 12.2 mo in patients achieving BNI-I and BNI > I, respectively (P = .046). Among 210 patients with known status of post-SRS complications, the new-onset of facial numbness (BNI-I or II) after SRS occurred in 21 patients (10%).

In this largest series SRS offers a reasonable benefit to risk profile for patients who have exhausted medical management. More favorable initial response to SRS may predict a long-lasting pain control 8).

2016

One hundred seventeen patients with medically refractory TN treated by GKRS at the Department of Functional Neurosurgery and Gamma Knife Radiosurgery, and Department of Neurology, Ruber International Hospital, Madrid, Spain were followed up between 1993 and 2011. Mean maximum dose was 86.5 Gy (range: 80-90 Gy; median: 90 Gy). Clinical response was defined based on the Burchiel classification. They considered classes I and II as a complete response. For toxicity, they use the Barrow Neurological Institute Pain Scale. Mean duration of follow-up was 66 months (range: 24-171 months).

Complete response at last follow-up in our patients was 81%, with an excellent response while off medication in 52%. Pain-free rates without medication (class I) were 85% at 3 years (confidence interval [CI]: 78%-94%), 81% at 5 years (CI: 72%-91%), and 76% at 7 years (CI: 65%-90%). Complete response rates (classes I-II) were 91% at 3 years (CI: 86%-97%), 86% at 5 years (CI: 79%-93%), and 82% at 7 years (CI: 72%-93%). Poor treatment response rates differed significantly between patients who had undergone previous surgery and were refractory to management with medication prior to GKRS. New or worsening facial numbness was reported in 32.5% (30% score II and 2.5% score III). No anesthesia dolorosa was reported. Permanent recurrence pain rate was 12%.

GKRS achieved favorable outcomes compared with surgery in terms of pain relief and complication rates in our cohort of patients, notwithstanding decreasing pain-free survival rates over time. They consider GKRS to be an initial treatment in the management of medically intractable TN in selected patients 9).


In a single-center, retrospective comparative study, 202 patients with MS and concomitant TN were evaluated. A minimum follow-up of 24 months was required. Patients with a history of microvascular decompression or previous intervention were excluded. There were 78 PBC procedures performed and 124 first-dosage GKRS procedures for a total of 202 patients between February 2009 and December 2013. The PBC procedures were successfully completed in all cases. The two groups were compared with regards to initial effect, duration of effect, and rate of complication(s), including the type and severity of the complication(s).

Immediate pain relief resulted in 87% of patients treated with PBC and in 23% of patients treated with GKRS. The Kaplan-Meier plots for the two treatment modalities were similar. The 50% recurrence rate was at 12 months for the PBC and 18 months for the GKRS. The rates of complication (excluding numbness) were 3% for GKRS and 21% for PBC. The difference was statistically significant (Chi-square test, p = 0.03).

PBC and GKRS are effective techniques for the treatment of TN in patients with MS, with GKRS presenting fewer complications and superior long-term relief. For these reasons, we consider GKRS as the first option for the treatment of TN in MS patients, reserving PBC for patients with acute, intractable pain 10).

Case reports

A 72-year-old -female presented with trigeminal neuralgia (TN) and radiological evidence of neurovascular compression on the affected side. She had complete resolution of her pain for 7 years after treatment with GKRS. The patient experienced recurrence and underwent repeat GKRS, this time resulting in another 3 years of pain relief. After the second recurrence, repeat intracranial imaging demonstrated resolution of neurovascular compression.

GKRS is an important treatment option for TN, although the mechanisms behind pain relief from this procedure still remain unclear. While prior histological and radiological studies point to ablative mechanisms for pain relief, this case report suggests that GKRS may result in a decompressive effect in TN due to changes in neurovascular architecture. Despite this finding, TN is known to occur and recur in the absence of neurovascular compression; thus, further work is necessary to understand the etiology of TN and its treatments.

In this case, Moosa et al. demonstrated that vessel-nerve relationships may change over time in TN patients treated with GKRS, which raises the possibility that GKRS could release a neurovascular compression 11).

References

1)

Lunsford LD. Comment on Taha J M and Tew J M: Comparison of Surgical Treatmen ts for Trigemin al Neuralgia: Reevaluation of Radiofrequency Rhizotomy. Neurosurgery. 1996; 38
2)

Descovich M, Sneed PK, Barbaro NM, McDermott MW, Chuang CF, Barani IJ, Nakamura JL, Lijun M. A dosimetric comparison between Gamma Knife and CyberKnife treatment plans for trigeminal neuralgia. J Neurosurg. 2010 Dec;113 Suppl:199-206. PubMed PMID: 21222296.
3)

Brisman R. Gamma knife surgery with a dose fo 75 to 76.8 Gray for trigeminal neuralgia. J Neurosurg. 2004; 100:848–854
4)

Pollock BE, Phuong LK, Foote RL, Sta ord SL, Gorman DA. High-dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery. 2001; 49:58–62; discussion 62-4
5)

Kondziolka D, Lunsford LD, Flickinger JC. Stereotact ic radiosurgery for the treatment of trigeminal neuralgia. Clin J Pain. 2002; 18:42–47
6)

Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotch i J, Levivier M. Gamma kn ife surgery for idiopathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg. 2004; 100:597–605
7)

Urgosik D, Liscak R, Novotny J, Jr, Vymazal J, Vladyka V. Treatment of essential trigeminal neuralgia with gamma knife surgery. J Neurosurg. 2005; 102 Suppl:29–33
8)

Xu Z, Mathieu D, Heroux F, Abbassy M, Barnett G, Mohammadi AM, Kano H, Caruso J, Shih HH, Grills IS, Lee K, Krishnan S, Kaufmann AM, Lee JYK, Alonso-Basanta M, Kerr M, Pierce J, Kondziolka D, Hess JA, Gerrard J, Chiang V, Lunsford LD, Sheehan JP. Stereotactic Radiosurgery for Trigeminal Neuralgia in Patients With Multiple Sclerosis: A Multicenter Study. Neurosurgery. 2019 Feb 1;84(2):499-505. doi: 10.1093/neuros/nyy142. PubMed PMID: 29688562.
9)

Martínez Moreno NE, Gutiérrez-Sárraga J, Rey-Portolés G, Jiménez-Huete A, Martínez Álvarez R. Long-Term Outcomes in the Treatment of Classical Trigeminal Neuralgia by Gamma Knife Radiosurgery: A Retrospective Study in Patients With Minimum 2-Year Follow-up. Neurosurgery. 2016 Dec;79(6):879-888. PubMed PMID: 27560193.
10)

Alvarez-Pinzon AM, Wolf AL, Swedberg HN, Barkley KA, Cucalon J, Curia L, Valerio JE. Comparison of Percutaneous Retrograsserian Balloon Compression and Gamma Knife Radiosurgery for the Treatment of Trigeminal Neuralgia in Multiple Sclerosis: A Clinical Research Study Article. World Neurosurg. 2016 Oct 15. pii: S1878-8750(16)31016-6. doi: 10.1016/j.wneu.2016.10.028. PubMed PMID: 27756676.
11)

Moosa S, Wang TR, Mastorakos P, Sheehan JP, Elias WJ. Gamma Knife Radiosurgery for Trigeminal Neuralgia Reduces Neurovascular Compression: A Case Report after 11 Years. Stereotact Funct Neurosurg. 2019 Sep 5:1-5. doi: 10.1159/000501624. [Epub ahead of print] PubMed PMID: 31487732.
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