Lactotroph Adenoma Surgery

Lactotroph Adenoma Surgery

Lactotroph Adenoma Surgery is safe and efficient. It is particularly suitable for enclosed prolactinomas. The patient should be well informed of the pros and cons of the treatment options, which include dopamine agonist (DA) and transsphenoidal microsurgery, and the patient’s preference should be taken into account during decision-making 1).

In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonist2).

Prolactin level < 500 ng/ml in prolactinomas that are not extensively invasive: PRL may be normalized with surgery.


PRL > 500 ng/ml: the chances of normalizing PRL surgically are very low 3).

If no acute progression, an initial attempt of medical therapy should be made as the chances of normalizing PRL surgically with preop levels > 500 ng/ml are very low 4) (these tumors may shrink dramatically with bromocriptine).

If tumor not controlled medically (≈ 18 % will not respond to bromocriptine: surgery followed by restitution of medical therapy may normalize PRL).


Barrow et al. reviewed the results of transsphenoidal microsurgical management in 69 patients with prolactin-secreting pituitary adenomas who had preoperative serum prolactin levels over 200 ng/ml. The patients were divided into three groups based on their preoperative serum prolactin levels: over 200 to 500 ng/ml (Group A); over 500 to 1000 ng/ml (Group B); and over 1000 ng/ml (Group C). The percentage of successful treatment (“control rate”) was 68%, 30%, and 14%, respectively, in these three groups of patients. Based on these results, the authors offer guidelines for the management of patients with prolactin-secreting pituitary adenomas associated with exceptionally high serum prolactin levels. The surgical control rate of 68% in Group A seems to justify surgery for these patients, while primary medical care with bromocriptine is recommended for most patients with serum prolactin levels over 500 ng/ml 5).


Dopamine agonist therapy is the first line of treatment for prolactinomas because of its effectiveness in normalizing serum prolactin levels and shrinking tumor size. Though withdrawal of dopamine agonist treatment is safe and may be implemented following certain recommendations, recurrence of disease after cessation of the drug occurs in a substantial proportion of patients. Concerns regarding the safety of dopamine agonists have been raised, but its safety profile remains high, allowing its use during pregnancy. Surgery is typically indicated for patients who are resistant to medical therapy or intolerant of its adverse side effects, or are experiencing progressive tumor growth. Surgical resection can also be considered as a primary treatment for those with smaller focal tumors where a biochemical cure can be expected as an alternative to lifelong dopamine agonist treatment. Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy 6).


Many guidelines and reports that caution against surgical treatment are based on data over a decade or more old using different techniques such as microsurgical transsphenoidal surgery or from the nascent era of endoscopic transphenoidal surgery 7).

Endoscopic techniques have continued to evolve and provide for excellent visualization, low CSF leak rates, and high rates of gross total resection. In a study of DA-resistant prolactinomas, Vroonen et al. showed that surgical debulking led to a significant de- crease in prolactin levels at a significantly lower DA dose 8).

Kreutzer et al. report a remission rate of 91 % in patients who had elective surgery of microprolactinomas, and Babey et al. also had a high long-term remission rate, without morbidity or mortality for patients with microprolactinomas 9) 10).

Cost considerations are also a concern, especially in countries such as the USA, which is undergoing rapid changes in its healthcare system. A study by Jethwa and Patel et al. found surgical resection of microprolactinomas to be more cost effective long term than medical therapy 11).


Tumor size and invasion of extrasellar and/or cavernous sinuses have typically been seen as limitations of surgery, and some patients with refractory very large or giant tumors may necessitate multistage surgical procedures with a combi- nation of endonasal and transcranial approaches.

see Lactotroph adenoma radiosurgery.


Expanded endoscopic endonasal techniques have been developed that allow for safe treatment of larger adenomas that have extra-/parasellar extension as long as the extension is in the cranio-caudal direction and not lateral to the carotids. However, the issue of partial resection and the risk of apoplexy in the residual irritated tumor is of some concern. As in many other areas of neuro-oncology, a combination approach may be optimal. Surgical resection may allow for definitive removal of the tumor and relief of the mass effect and provide tissue for precisely targeted therapies to prevent recurrence. Sophisticated immunohistochemistry and genetic testing are rapidly being applied to many other tumors and may in the future allow for superior targeted adjuvant therapies in prolactinomas and help reduce recurrences. Finally, surgery might be an answer to the long-term cost of medical therapy specifically in younger patients. However, this issue should be carefully assessed on an individual basis to not jeopardize the standard of care in prolactinoma management by unnecessary surgical treatment. Medical treatment remains the first and the treatment of choice in the general population with recently diagnosed prolactinoma in the absence of rapidly progressive neurological symptoms 12).

Few studies address the cost of treating prolactinomas.

The Department of Neurological Surgery, University of California at San Francisco, performed a cost-utility analysis of surgical versus medical treatment for prolactinomas. Materials and Methods We determined total hospital costs for surgically and medically treated prolactinoma patients. Decision-tree analysis was performed to determine which treatment produced the highest quality-adjusted life years (QALYs). Outcome data were derived from published studies. Results Average total costs for surgical patients were $19,224 ( ± 18,920). Average cost for the first year of bromocriptine or cabergoline treatment was $3,935 and $6,042, with $2,622 and $4,729 for each additional treatment year. For a patient diagnosed with prolactinoma at 40 years of age, surgery has the lowest lifetime cost ($40,473), followed by bromocriptine ($41,601) and cabergoline ($70,696). Surgery also appears to generate high health state utility and thus more QALYs. In sensitivity analyses, surgery appears to be a cost-effective treatment option for prolactinomas across a range of ages, medical/surgical costs, and medical/surgical response rates, except when surgical cure rates are ≤ 30%. Conclusion Our single institution analysis suggests that surgery may be a more cost-effective treatment for prolactinomas than medical management for a range of patient ages, costs, and response rates. Direct empirical comparison of QALYs for different treatment strategies is needed to confirm these findings 13).


1)

Giese S, Nasi-Kordhishti I, Honegger J. Outcomes of Transsphenoidal Microsurgery for Prolactinomas – A Contemporary Series of 162 Cases. Exp Clin Endocrinol Diabetes. 2021 Jan 18. doi: 10.1055/a-1247-4908. Epub ahead of print. PMID: 33461233.
2)

Zamanipoor Najafabadi AH, Zandbergen IM, de Vries F, et al. Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis. J Clin Endocrinol Metab. 2020;105(3):e32‐e41. doi:10.1210/clinem/dgz144
3) , 4) , 5)

Barrow DL, Mizuno J, Tindall GT. Management of prolactinomas associated with very high serum prolactin levels. J Neurosurg. 1988 Apr;68(4):554-8. PubMed PMID: 3351583.
6)

Wong A, Eloy JA, Couldwell WT, Liu JK. Update on prolactinomas. Part 2: Treatment and management strategies. J Clin Neurosci. 2015 Oct;22(10):1568-74. doi: 10.1016/j.jocn.2015.03.059. Epub 2015 Aug 1. Review. PubMed PMID: 26243714.
7)

Casanueva FF, Molitch ME, Schlechte JA, Abs R, Bonert V, Bronstein MD, Brue T, Cappabianca P, Colao A, Fahlbusch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, Laws E, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A (2006) Guidelines of the pituitary society for the diagnosis and management of prolactinomas. Clin Endocrinol 65:265–273
8)

Vroonen L, Jaffrain-Rea ML, Petrossians P, Tamagno G, Chanson P, Vilar L, Borson-Chazot F, Naves LA, Brue T, Gatta B, Delemer B, Ciccarelli E, Beck-Peccoz P, Caron P, Daly AF, Beckers A (2012) Prolactinomas resistant to standard doses of cabergoline: a multicen- ter study of 92 patients. Eur J Endocrinol 167:651–662
9)

Babey M, Sahli R, Vajtai I, Andres RH, Seiler RW (2011) Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists. Pituitary 14:222–230
10)

Kreutzer J, Buslei R, Wallaschofski H, Hofmann B, Nimsky C, Fahlbusch R, Buchfelder M (2008) Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. Eur J Endocrinol 158:11–18
11)

Jethwa PR, Patel TD, Hajart AF, Eloy JA, Couldwell WT, Liu JK (2015) Cost-effectiveness analysis of microscopic and endoscopic transsphenoidal surgery versus medical therapy in the management of microprolactinoma in the United States. World Neurosurg 5:2015
12)

Chakraborty S, Dehdashti AR. Does the medical treatment for prolactinoma remain the standard of care? Acta Neurochir (Wien). 2016 May;158(5):943-4. doi: 10.1007/s00701-016-2763-y. Epub 2016 Mar 11. PubMed PMID: 26965287.
13)

Zygourakis CC, Imber BS, Chen R, Han SJ, Blevins L, Molinaro A, Kahn JG, Aghi MK. Cost-Effectiveness Analysis of Surgical versus Medical Treatment of Prolactinomas. J Neurol Surg B Skull Base. 2017 Apr;78(2):125-131. doi: 10.1055/s-0036-1592193. Epub 2016 Sep 27. PubMed PMID: 28321375; PubMed Central PMCID: PMC5357228.

Cavernous sinus hemangioma Gamma Knife surgery

Cavernous sinus hemangioma Gamma Knife surgery

A study aimed to evaluate the efficacy of Gamma Knife surgery (GKS) on cavernous sinus hemangioma and to analyze the temporal volume change.

Cho et al. retrospectively reviewed the clinical data of 26 cavernous sinus hemangioma patients who were treated with GKS between 2001 and 2017. Before GKS, 11 patients (42.3%) had cranial neuropathies and 5 patients (19.2%) complained of headache, whereas 10 patients (38.5%) were initially asymptomatic. The mean pre-GKS mass volume was 9.3 mL (range, 0.5-31.6 mL), and the margin dose ranged from 13 to 15 Gy according to the mass volume and the proximity to the optic pathway. All cranial neuropathy patients and half of headache patients showed clinical improvement. All 26 patients achieved mass control; remarkable responses (less than 1/3 of the initial mass volume) were shown in 19 patients (73.1%) and moderate responses (more than 1/3 and less than 2/3) in 7 patients (26.9%). The mean final mass volume after GKS was 1.8 mL (range, 0-12.6 mL). The mean mass volume at 6 months after GKS was 45% (range, 5-80%) compared to the mass volume before GKS and 21% (range, 0-70%) at 12 months. The higher radiation dose tended to induce more rapid and greater volume reduction. No treatment-related complication was observed during the follow-up period. GKS could be an effective and safe therapeutic strategy for CSCH. GKS induced very rapid volume reduction compared to other benign brain tumors 1).


An international multicenter study was conducted to review outcome data in 31 patients with CSH. Eleven patients had initial microsurgery before SRS, and the other 20 patients (64.5%) underwent Gamma Knife SRS as the primary management for their CSH. Median age at the time of radiosurgery was 47 years, and 77.4% of patients had cranial nerve dysfunction before SRS. Patients received a median tumor margin dose of 12.6 Gy (range 12-19 Gy) at a median isodose of 55%. RESULTS Tumor regression was confirmed by imaging in all 31 patients, and all patients had greater than 50% reduction in tumor volume at 6 months post-SRS. No patient had delayed tumor growth, new cranial neuropathy, visual function deterioration, adverse radiation effects, or hypopituitarism after SRS. Twenty-four patients had presented with cranial nerve disorders before SRS, and 6 (25%) of them had gradual improvement. Four (66.7%) of the 6 patients with orbital symptoms had symptomatic relief at the last follow-up. CONCLUSIONS Stereotactic radiosurgery was effective in reducing the volume of CSH and attaining long-term tumor control in all patients at a median of 40 months. The authors’ experience suggests that SRS is a reasonable primary and adjuvant treatment modality for patients in whom a CSH is diagnosed. 2).


Between August 2011 and April 2014, 7 patients with CSHs underwent GKS. GKS was performed as the sole treatment option in 5 patients, whilst partial resection had been performed previously in 1 patient and biopsy had been performed in 1 patient. The mean volume of the tumors at the time of GKS was 12.5±10.2 cm3 (range, 5.3-33.2 cm3), and the median prescription of peripheral dose was 14.0 Gy (range, 10.0-15.0 Gy). The mean follow-up period was 20 months (range, 6-40 months). At the last follow-up, the lesion volume had decreased in all patients, and all cranial neuropathies observed prior to GKS had improved. There were no radiation-induced neuropathies or complications during the follow-up period. GKS appears to be an effective and safe treatment modality for the management of CSHs 3).


A retrospective analysis of 7 patients with CS hemangiomas treated by GKS between 1993 and 2008. Data from 84 CS meningiomas treated during the same period were also analyzed for comparison. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Data on clinical and imaging changes after radiosurgery were analyzed.

Six months after GKS, magnetic resonance imaging revealed an average of 72% tumor volume reduction (range, 56%-83%). After 1 year, tumor volume decreased 80% (range, 69%-90%) compared with the pre-GKS volume. Three patients had > 5 years of follow-up, which showed the tumor volume further decreased by 90% of the original size. The average tumor volume reduction was 82%. In contrast, tumor volume reduction of the 84 cavernous sinus meningiomas after GKS was only 29% (P < .001 by Mann-Whitney U test). Before treatment, 6 patients had various degrees of ophthalmoplegia. After GKS, 5 improved markedly within 6 months. Two patients who suffered from poor vision improved after radiosurgery.

GKS is an effective and safe treatment modality for CS hemangiomas with long-term treatment effect. Considering the high risks involved in microsurgery, GKS may serve as the primary treatment choice for CS hemangiomas 4).


1)

Cho JM, Sung KS, Jung IH, Chang WS, Jung HH, Chang JH. Temporal Volume Change of Cavernous Sinus Cavernous Hemangiomas after Gamma Knife Surgery. Yonsei Med J. 2020 Nov;61(11):976-980. doi: 10.3349/ymj.2020.61.11.976. PMID: 33107242.
2)

Lee CC, Sheehan JP, Kano H, Akpinar B, Martinez-Alvarez R, Martinez-Moreno N, Guo WY, Lunsford LD, Liu KD. Gamma Knife radiosurgery for hemangioma of the cavernous sinus. J Neurosurg. 2017 May;126(5):1498-1505. doi: 10.3171/2016.4.JNS152097. Epub 2016 Jun 24. PMID: 27341049.
3)

Xu Q, Shen J, Feng Y, Zhan R. Gamma Knife radiosurgery for the treatment of cavernous sinus hemangiomas. Oncol Lett. 2016 Feb;11(2):1545-1548. doi: 10.3892/ol.2015.4053. Epub 2015 Dec 23. PMID: 26893777; PMCID: PMC4734249.
4)

Chou CW, Wu HM, Huang CI, Chung WY, Guo WY, Shih YH, Lee LS, Pan DH. Gamma knife surgery for cavernous hemangiomas in the cavernous sinus. Neurosurgery. 2010 Sep;67(3):611-6; discussion 616. doi: 10.1227/01.NEU.0000378026.23116.E6. PMID: 20647963.

Chronic subdural hematoma surgery complications

Chronic subdural hematoma surgery complications

The most frequent complication after chronic subdural hematoma (CSDH) is chronic subdural hematoma recurrence requiring reoperation. Although several definitions of recurrence have been proposed 1) one of the most consensual definitions of recurrence is the association between new clinical symptoms and hematoma revealed by CT scans. Thus, one can wonder whether a systematic CT scan is necessary after CSDH evacuation for a patient without symptoms.

Common postoperative complications include acute epidural and/or subdural bleeding, tension pneumocephalusintracranial hematomas and ischemic cerebral infarction.

Failure of the brain to re-expand, pneumocephalus, incomplete evacuation, and recurrence of the fluid collection are the most frequently.

Recurrence

see Chronic subdural hematoma recurrence.

Seizures

Seizures (including intractable status epilepticus).

Intracerebral hemorrhage

Intracerebral hemorrhage (ICH): occurs in 0.7–5%. Very devastating in this setting: one–third of these patients die and one third are severely disabled

Brain herniation

Chronic subdural hematoma (CSDH) with brain herniation signs is rarely seen in the emergent department. As such, there are few cumulative data to analyze such cases.

Failure of postoperative cerebral reexpansion

A wide variation in postoperative drainage volumes is observed during treatment of chronic subdural hematoma (CSDH) with twist-drill or burr-hole craniostomy and closed-system drainage.

The postoperative drainage volumes varied greatly because of differences in the outer membrane permeability of CSDH, and such variation seems to be related to the findings on the CT scans obtained preoperatively. Patients with CSDH in whom there is less postoperative drainage than expected should be carefully observed, with special attention paid to the possibility of recurrence 2).

Patients with high subdural pressure showed the most rapid brain expansion and clinical improvement during the first 2 days. Nevertheless, a computerized tomography (CT) scan performed on the 10th day after surgery demonstrated persisting subdural fluid in 78% of cases. After 40 days, the CT scan was normal in 27 of the 32 patients. There was no mortality and no significant morbidity. A study suggests that well developed subdural neomembranes are the crucial factors for cerebral reexpansion, a phenomenon that takes at least 10 to 20 days. However, blood vessel dysfunction and impairment of cerebral blood flow may participate in delay of brain reexpansion. It may be argued that additional surgical procedures, such as repeated tapping of the subdural fluid, craniotomy, and membranectomy or even craniectomy, should not be evaluated earlier than 20 days after the initial surgical procedure unless the patient has deteriorated markedly 3).

Postoperative pneumocephalus

see Tension pneumocephalus after chronic subdural hematoma evacuation.

Remote cerebellar hemorrhage (RCH)

see Remote cerebellar hemorrhage.

Epidural hematoma

After chronic subdural hematoma evacuation surgery, the development of epidural hematoma is a very rare entity.

Akpinar et al. report the case of a 41-year-old man with an epidural hematoma complication after chronic subdural hematoma evacuation. Under general anesthesia, the patient underwent a large craniotomy with closed system drainage performed to treat the chronic subdural hematoma. After chronic subdural hematoma evacuation, there was epidural leakage on the following day.

Although trauma is the most common risk factor in young CSDH patients, some other predisposing factors may exist. Intracranial hypotension can cause EDH. Craniotomy and drainage surgery can usually resolve the problem. Because of rapid dynamic intracranial changes, epidural leakages can occur. A large craniotomy flap and silicone drainage in the operation area are key safety points for neurosurgeons and hydration is essential 4).

Intracranial subdural empyema

A case of intracranial subdural empyema following chronic subdural hematoma drainage 5).

Skin depression

see Skin depression after chronic subdural hematoma surgery.

Oculomotor nerve palsy

see Oculomotor nerve palsy in chronic subdural hematoma.

Pseudohypoxic brain swelling

Pseudohypoxic brain swelling (PHBS) is a rare and potentially fatal complication that may occur in patients following uneventful brain surgery. Fan presented a case of PHBS after chronic subdural hematoma surgery that developed after drilling and drainage. Neuroimaging findings, pathogenic factors, and therapy are also discussed 6).

References

1)

A. Chiari, K. Hocking, E. Broughton, C. Turner, T. Santarius, P. Hutchinson, A. Kolias, Core outcomes and common data elements in chronic subdural hematoma: a systematic review of the literature focused on reported outcomes, J.Neurotrauma 33 (2016) 1212–1219, https://doi.org/10.1089/neu.2015.3983.
2)

Kwon TH, Park YK, Lim DJ, Cho TH, Chung YG, Chung HS, Suh JK. Chronic subdural hematoma: evaluation of the clinical significance of postoperative drainage volume. J Neurosurg. 2000 Nov;93(5):796-9. PubMed PMID: 11059660.
3)

Markwalder TM, Steinsiepe KF, Rohner M, Reichenbach W, Markwalder H. The course of chronic subdural hematomas after burr-hole craniostomy and closed-system drainage. J Neurosurg. 1981 Sep;55(3):390-6. PubMed PMID: 7264730.
4)

Akpinar A, Ucler N, Erdogan U, Yucetas CS. Epidural Hematoma Complication after Rapid Chronic Subdural Hematoma Evacuation: A Case Report. Am J Case Rep. 2015 Jul 6;16:430-433. PubMed PMID: 26147957.
5)

Ovalioglu AO, Aydin OA. A case of subdural empyema following chronic subdural hematoma drainage. Neurol India. 2013 Mar-Apr;61(2):207-9. doi: 10.4103/0028-3886.111165. PubMed PMID: 23644343.
6)

Fan Q. Pseudohypoxic Brain Swelling after Drilling and Drainage for Chronic Subdural Hematoma. J Neurol Surg A Cent Eur Neurosurg. 2020 Oct 13. doi: 10.1055/s-0040-1712500. Epub ahead of print. PMID: 33049793.
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