Conflicts of interest

Conflicts of interest

Definition

The Institute of Medicine (IOM) defines conflict of interest as “circumstances that create a risk that professional judgments or actions regarding a primary interest will be unduly influenced by a secondary interest” 1).


Developmental incentives are fundamental to surgical progress, yet financial and professional incentives inherently create conflicts of interest(COI). Understanding how to manage COI held by neurosurgeons, industryhospitals, and journal editors, without thwarting progress and innovation is critical.

A review of the literature was performed to assess conflicts of interest that affect neurosurgical innovation, and review ways to manage COI of various parties while adhering to ethical standards.

COI are inherent to collaboration and innovation, and are therefore an unavoidable component of neurosurgery. The lack of a clear distinction between clinical practice and innovation, ability to use devices off-label, and unstandardized disclosure requirements create inconsistencies in the way that conflicts of interest are handled. Additionally, lack of requirements to compare innovation to the standard of care and inherent bias that affects study design and interpretation can have profound effects on the medical literature. Conflicts of interest can have both direct and downstream effects on neurosurgical practice, and it is possible to manage them while improving the quality of research and innovation.

Conflicts of interest are inherent to surgical innovation, and can be handled in an ethically sound manner. Neurosurgeons, device companieshospitals, and medical journals can take steps to proactively confront bias and ensure patient autonomy and safety. These steps can preserve public trust and ultimately improve evidence-based neurosurgical practice 2).

Relationships

Financial and nonfinancial relationships between pharmaceutical or medical device industry, physicians, investigators, and academic institutions are common and generally considered essential for development of new technology and advancement in medicine 3) 4).

However, these ties may at the same time create conflicts of interest: a set of circumstances that creates a risk that professional judgments or actions regarding a primary interest will be unduly influenced by a secondary interest 5).

Industry’s interests

The health care industry-manufacturers of drugs, devices, and medical equipment and its associated political and lobbying power, heavily influence strategic directions in clinical research. They may intervene, through experts with disclosed or silenced financial industry ties, in clinical guideline formation and dissemination, and may ultimately affect daily clinical practice.

The industry’s interests are not necessarily aligned with the interests of patients and society and may lead to study participant injury or harm and also reduce the public’s trust and confidence in clinical research.

It is obvious that the growing number of clinical trials conducted in vulnerable countries requires commitment from all stakeholders to ensure adherence to a core of internationally accepted ethical principles that reflect one of the basic ethical premises of the Declaration of Helsinki; that is, that the interests of science and society are not an excuse to conduct clinical trials in vulnerable countries.

Transnational clinical research should be controlled by internationally accredited ethical review boards, and research protocols rejected in one country should not be given permission to proceed elsewhere.

In addition, international human research monitoring agencies should have “…the power to sanction corporations and research groups that fail to respect universal standards”.

While these mechanisms are implemented, the role of major journals publishing the results of RCTs is crucial. This is because, as Smith emphasizes, when results are published in a major journal, the study receives “…the journal’s stamp of approval”, the published results carry a kind of professional approbation, and the paper becomes more attractive to both the readers and media, who may amplify the real value of the results.


A study aimed to determine the prevalence and financial magnitude of potential conflict of interest among editorial board members of five leading spine journals. The editorial boards of: The Spine Journal; Spine; European Spine Journal; Journal of Neurosurgery: Spine; and Journal of Spinal Disorders & Techniques were extracted on January 2013 from the journals’ websites. Disclosure statements were retrieved from the 2013 disclosure index of the North American Spine Society; the program of the 20th International Meeting on Advanced Spine Techniques; the program of the 48th Annual Meeting of the Scoliosis Research Society; the program of the AOSpine global spine congress; the presentations of the 2013 Annual Eurospine meeting; and the disclosure index of the American Academy of Orthopaedic Surgeons. Names of the editorial board members were compared with the individuals who completed a disclosure for one of these indexes. Disclosures were extracted when full names matched. Two hundred and ten (29%) of the 716 identified editorial board members reported a potential conflict of interest and 154 (22%) reported nothing to disclose. The remaining 352 (49%) editorial board members had no disclosure statement listed for one of the indexes. Eighty-nine (42%) of the 210 editorial board members with a potential conflict of interest reported a financial relationship of more than $10,000 during the prior year. This finding confirms that potential conflicts of interest exist in editorial boards which might influence the peer review process and can result in bias. Academia and medical journals in particular should be aware of this and strive to improve transparency of the review process. Janssen et al. emphasize recommendations that contribute to achieving this goal 6).


Traditional peer-review processes used by journal editors to aid in deciding which papers are worth publishing is not capable of filtering some of the more sophisticated techniques of covered marketing and conflicts of interest. The incorporation of ethicists in the peer review process would likely help to raise red flags and to properly consider the routine statement that the study was accepted by the “human review board” of some prestigious university. By rejecting suspicious ethical studies, editors may not be able to help make the world a fairer place, but they will help in building a healthier scientific community and sending a clear message, to both scientists and the industry, that it is unacceptable to exploit and potentially harm a few people for the sake of many 7).

Surgeon-industry

Surgeon-industry conflict of interest (COI) has become a source of considerable interest. Professional medical societiesindustry, and policy makers have attempted to regulate potential COI without consideration for public opinion.

The objective of a study was to report on the opinions of individuals representing the general public regarding surgeon-industry consulting relationships.

Survey was administered using a “spine Web site,” and opinions are collected on surgeon-industry consulting and regulation. Associations among responses to similar questions were assessed to ensure validity and subgroup analysis performed for respondent age, sex, education, insurance, employment, and patient status.

Six hundred ten of 642 surveys had complete data. The sample population comprised more females and was older and more educated than the American population. About 80% of respondents felt it was ethical and either beneficial or of no influence to the quality of health care if surgeons were consultants for surgical device companies. Most felt disclosure of an industry relationship was important and paying surgeons royalties for devices, other than those they directly implant, would not affect quality of care. Respondents support multidisciplinary surgeon-industry COI regulation and trust doctors and their professional societies to head this effort.

Despite the known potential negative impact of surgeon-industry COI on patient care, this study revealed that this does not seem to be reflected in the opinion of the general public. The respondents felt that disclosure is deemed one of the most important means of self-regulation and COI management, which is in agreement with current trends of most spine societies and journals that are increasing the stringency of disclosure policies 8).

Editorial board members of medical journals

Conflicts of interest arising from ties between pharmaceutical industry and physicians are common and may bias research. The extent to which these ties exist among editorial board members of medical journals is not known.

A study aims to determine the prevalence and financial magnitude of potential conflicts of interest among editorial board members of five leading spine journals. The editorial boards of: The Spine Journal; Spine; European Spine Journal; Journal of Neurosurgery: Spine; and Journal of Spinal Disorders & Techniques were extracted on January 2013 from the journals’ websites. Disclosure statements were retrieved from the 2013 disclosure index of the North American Spine Society; the program of the 20th International Meeting on Advanced Spine Techniques; the program of the 48th Annual Meeting of the Scoliosis Research Society; the program of the AOSpine global spine congress; the presentations of the 2013 Annual Eurospine meeting; and the disclosure index of the American Academy of Orthopaedic Surgeons. Names of the editorial board members were compared with the individuals who completed a disclosure for one of these indexes. Disclosures were extracted when full names matched. Two hundred and ten (29%) of the 716 identified editorial board members reported a potential conflict of interest and 154 (22%) reported nothing to disclose. The remaining 352 (49%) editorial board members had no disclosure statement listed for one of the indexes. Eighty-nine (42%) of the 210 editorial board members with a potential conflict of interest reported a financial relationship of more than $10,000 during the prior year. This finding confirms that potential conflicts of interest exist in editorial boards which might influence the peer review process and can result in bias. Academia and medical journals in particular should be aware of this and strive to improve transparency of the review process. Janssen et al. emphasize recommendations that contribute to achieving this goal 9).

Physician fully employed by industry

We would not allow a physician fully employed by industry to make a scientific presentation or publish an article for a peer-reviewed journal related to his or her company’s device or drug, yet we know from previously released orthopedic surgeon related data that many physician lecturers and writers are receiving yearly “consulting fees” and “royalty arrangements” that greatly exceed what is paid to physicians employed by device manufacturers—many above $1 million/year 10) 11) 12).

If publicly reporting these numbers places some in an uncomfortable position, so be it. This information is critical in the analysis of the clarity, sanctity, and scientific integrity of information and data presented. Collaboration has been valuable, but full transparency is critical to open, unbiased scientific dialogue and exchange.

References

1)

IOM (Institute of Medicine) Conflict of interest in medical research, education, and practice. Washington, DC: National Academies Press; 2009.
2)

DiRisio AC, Muskens IS, Cote DJ, Babu M, Gormley WB, Smith TR, Moojen WA, Broekman ML. Oversight and Ethical Regulation of Conflicts of Interest in Neurosurgery in the United States. Neurosurgery. 2019 Feb 1;84(2):305-312. doi: 10.1093/neuros/nyy227. PubMed PMID: 29850841.
3)

Bekelman JE, Li Y, Gross CP. Scope and impact of financial conflicts of interest in biomedical research: a systematic review. JAMA. 2003; 289: 454–465.
4)

Garfin SR. Spine surgeons: spine industry. Eur Spine J. 2008; 17: 785–790.
5)

Steering Committee on Science and Creationism: National Academy of Sciences (1999) Science and Creationism: A View from the National Academy of Sciences, Second Edition The National Academies Press;
6) , 9)

Janssen SJ, Bredenoord AL, Dhert W, de Kleuver M, Oner FC, Verlaan JJ. Potential Conflicts of Interest of Editorial Board Members from Five Leading Spine Journals. PLoS One. 2015 Jun 4;10(6):e0127362. doi: 10.1371/journal.pone.0127362. eCollection 2015. PubMed PMID: 26042410.
7)

Sahuquillo J, Biestro A. Is intracranial pressure monitoring still required in the management of severe traumatic brain injury? Ethical and methodological considerations on conducting clinical research in poor and low-income countries. Surg Neurol Int. 2014 Jun 5;5:86. doi: 10.4103/2152-7806.133993. eCollection 2014. PubMed PMID: 25024886; PubMed Central PMCID: PMC4093744.
8)

DiPaola CP, Dea N, Noonan VK, Bailey CS, Dvorak MF, Fisher CG. Surgeon-industry conflict of interest: survey of North Americans’ opinions regarding surgeons consulting with industry. Spine J. 2014 Apr;14(4):584-91. doi: 10.1016/j.spinee.2013.06.028. Epub 2013 Aug 22. PubMed PMID: 23973098.
10)

Feder BJ. New focus of inquiry into bribes: doctors. New York Times. 2008 Mar 22; Available at: http://www.nytimes.com/2008/03/22/business/22device.html. Accessed December 30, 2010.
11)

Burns G. Partnerships between surgeons, implant makers raise ethical concerns. Chicago Tribune. 2008 Oct 26;
12)

Carryerou J, McGinty T. Top spine surgeons reap royalties, Medicare bounty. Wall Street Journal. 2010 Dec 20;:A1. Available at: http://online.wsj.com/article/SB10001424-052748703395204576024023361023138.html. Accessed December 30, 2010.

Intracranial epidermoid cyst

Intracranial epidermoid cyst

Epidemiology

Intracranial epidermoid cysts, are rare congenital lesions originating from the ectoderm that constitute 0.3 to 1.8 % of all intracranial neoplasms 1) 2).

The most common sites include

a) suprasellar: commonly produce bitemporal hemianopsia and optic atrophy, and only occasionally pituitary (endocrine) symptoms (including DI)

b) sylvian fissure: may present with seizures

c) cerebellopontine angle (CPA): may produce trigeminal neuralgia, especially in young patient

d) basilar-posterior fossa: may produce lower cranial nerve findings, cerebellar dysfunction, and/or corticospinal tract abnormalities

e) within the ventricular system: occur within the 4th ventricle more commonly than any other

Approximately half of these cysts are located at the cerebellopontine angle (CPA), although they can also be found in the parasellar regions, 4th ventricle, cerebellum, cerebral hemispheres, brainstem, and lateral ventricles.

see Cavernous sinus epidermoid

Cerebellopontine angle epidermoid cyst

Giant intracranial epidermoid.

Intradiploic epidermoid

Intraventricular epidermoid

Middle fossa epidermoid cyst

Pineal epidermoid cyst

Posterior fossa epidermoid cyst

Sylvian fissure epidermoid cyst.

Etiology

Intracranial epidermoid cysts, also known as primary cholesteatomas are considered to arise from epithelial inclusions at the time of neural tube closure or during formation of the secondary cerebral vesicles, and have slow growth rates resembling that of the normal epidermis 3).

Pathology

Pathologically, epidermoid cysts have well-circumscribed, irregular, thin walls with squamous epithelium lining. The epithelium undergoes progressive desquamation and keratin breakdown; therefore, the cystic contents include tissue debris, keratin, water, and solid cholesterol 4).

These tumors are congenital and arise from displaced epithelial tissue between the 3rd and 5th weeks of gestation, when neural tube closure occurs.

These brain lesions have an epithelial lining that encapsulates the tumor, which consists of desquamated epidermal cell debris. Most lesions are solid, but because the desquamated cells contain cholesterol some may have a liquid cystic center. The rate of tumor growth is gradual and linear, resembling the rate of human epidermis turnover, which is unlike the exponential growth of neoplastic lesions 5).

Diagnosis

Treatment

The treatment of choice for epidermoid cyst is a total resection of the tumor. But sometimes total resection is impossible because of anatomical complexity.

A conservative attitude in handling the tumor capsule is common given concerns about capsule adherence to neurovascular structures, and thus the possibility of recurrence is accepted with the intent of minimizing complications 6).

Outcome

Malignant transformation of an EC to squamous-cell carcinoma is rare; only 14 cases have been reported 7).

Case series

Vaz-Guimaraes et al., from Pittsburgh, Houston, and Toronto retrospectively reviewed the medical records of 21 patients who underwent endoscopic endonasal surgery for epidermoid and dermoid cyst resection at the University of Pittsburgh Medical Center between January 2005 and June 2014. Surgical outcomes and variables that might affect the extent of resection and complications were analyzed.

Total resection (total removal of cyst contents and capsule) was achieved in 8 patients (38.1%), near-total resection (total removal of cyst contents, incomplete removal of cyst capsule) in 9 patients (42.9%), and subtotal resection (incomplete removal of cyst contents and capsule) in 4 patients (19%). Larger cyst volume (≥ 3 cm3) and intradural location (15 cysts) were significantly associated with nontotal resection (p = 0.008 and 0.0005, respectively). In the whole series, surgical complications were seen in 6 patients (28.6%). No complications were observed in patients with extradural cysts. Among the 15 patients with intradural cysts, the most common surgical complication was postoperative CSF leak (5 patients, 33.3%), followed by postoperative intracranial infection (4 patients, 26.7%). Larger cysts and postoperative CSF leak were associated with intracranial infection (p = 0.012 and 0.028, respectively). Subtotal resection was marginally associated with intracranial infection when compared with total resection (p = 0.091). All patients with neurological symptoms improved postoperatively with the exception of 1 patient with unchanged abducens nerve palsy.

Endoscopic endonasal approaches may be effectively used for resection of epidermoid and dermoid cysts in carefully selected cases. These approaches are recommended for cases in which a total or near-total resection is possible in addition to a multilayer cranial base reconstruction with vascularized tissue to minimize the risk of intracranial infection 8).

References

1) , 3) , 4)

Kato K, Ujiie H, Higa T, Hayashi M, Kubo O, Okada Y, et al. Clinical presentation of intracranial epidermoids: a surgical series of 20 initial and four recurred cases. Asian J Neurosurg. 2010;5(1):32–40.
2)

Toglia JU, Netsky MG, Alexander E., Jr Epithelial (epidermoid) tumors of the cranium. Their common nature and pathogenesis. J Neurosurg. 1965;23(4):384–93. doi: 10.3171/jns.1965.23.4.0384.
5)

Alvord EC., Jr. Growth rates of epidermoid tumors. Ann Neurol. 1977;2:367–370.
6)

Aboud E, Abolfotoh M, Pravdenkova S, Gokoglu A, Gokden M, Al-Mefty O. Giant intracranial epidermoids: is total removal feasible? J Neurosurg. 2015 Jan 16:1-14. [Epub ahead of print] PubMed PMID: 25594324.
7)

Vellutini EA, de Oliveira MF, Ribeiro AP, Rotta JM. Malignant transformation of intracranial epidermoid cyst. Br J Neurosurg. 2014 Aug;28(4):507-9. doi: 10.3109/02688697.2013.869552. Epub 2013 Dec 18. Review. PubMed PMID: 24345076.
8)

Vaz-Guimaraes F, Koutourousiou M, de Almeida JR, Tyler-Kabara EC, Fernandez-Miranda JC, Wang EW, Snyderman CH, Gardner PA. Endoscopic endonasal surgery for epidermoid and dermoid cysts: a 10-year experience. J Neurosurg. 2018 Mar 1:1-11. doi: 10.3171/2017.7.JNS162783. [Epub ahead of print] PubMed PMID: 29547084.

Cavernous sinus meningioma

Cavernous sinus meningioma

Cavernous sinus (CS) meningiomas are by definition those supratentorial skull base meningiomas which originate from the parasellar region.

Meningiomas occupying the CS represent a heterogeneous group of tumors originating and extending over different anatomical skull base surfaces.

History

Initially, CSMs were deemed inoperable due to the considerable mortality and morbidity related to removal of the tumor from what was deemed a surgically inaccessible area. With the introduction of the operating microscope and advances in neuroimaging, resection of Cavernous sinus meningiomas became a realistic goal. The advances in Microneurosurgical procedures in the 1980s and early 1990s allowed attempts at aggressive resection of these tumors.

Since final 1990s, the enthusiasm for aggressive resection has been tempered and the pendulum has swung toward a more conservative surgical strategy for treating the tumors of the parasellar region. Major factors that seem to be responsible for this paradigm shift include the efficacy and safety of postoperative radiosurgery on subtotally resected meningiomas, histological evidence supporting cranial nerve (CN) infiltration by meningiomas, and greater consideration of the impact of postoperative outcomes on the patients’ quality of life 1) 2) 3)

Epidemiology

Cavernous sinus meningiomas (CSMs) occur in 0.5 per 100,000 persons in the general population.

There are an increasing number of asymptomatic patients with CSMs because CT scans or MR is commonly used for evaluation of other medical conditions, as cranial trauma and allows the diagnosis in the preclinical phase. 4).

Classification

Sekhar’s Classification

Grade I— tumors involve 1 region of the sinus & do not invoke the ICA

Grade II—tumors occupy multiple regions of the sinus & displace but do not encase the ICA

Grade III—tumors encase the ICA w/o narrowing

Grade IV—tumors encase & narrow the ICA

Grade V—tumors involve both CSs & encase the ICA

Sphenocavernous, clinoidocavernous, and sphenoclinoidocavernous meningiomas 5).


DeMonte’s grading of tumour resection

Grade Definition

I Complete removal of tumour and dural attachment with any abnormal bone

II Complete removal of tumour and coagulation of its dural attachment

IIIa Complete removal of intra- and extradural tumour without resection or coagulation of its dural attachment

IIIb Complete removal of intradural tumour without resection or coagulation of its dural attachment or any extradural tumour extensions

IVa Intentional subtotal removal to preserve cranial nerve or blood vessels with complete removal of its dural attachment

IVb Subtotal removal leaving <10% tumour volume V Subtotal removal leaving >10% tumour volume or decompression with or without biopsy 6).

Diagnosis

For deciding the most appropriate surgical strategy, surgeons need detailed preoperative neuroimaging. The vicinity of the tumor with the vital and highly functional neurovascular structures, tumor extensions into the basal cisterns and skull base structures, and the arterial vascularization and venous drainage pathways, as they shape operative strategy, are important preoperative data to take into account. Thin section CT scan with bone windows, 3D spiral CT reconstruction, MRI, MR angiography, and DSA performed with selective arteriography including late venous phases give those required detailed informations about the tumor and its relation with neurovascular and bony structures.

Treatment

Outcome

Despite technical advances regarding microsurgical resections of cavernous sinus meningiomas, they are rarely completely resected and are often accompanied by a high rate of neurological disturbances. After partial or subtotal tumour removal, the probability of recurrence remains significant (13% at 3 years; 38% at 5 years) 7)

The treatment of CSMs aims the best survival and local control coupled with the least possible morbidity. It includes close observation, surgical resection, radiotherapy, systemic therapy or a combination of these approaches. Management decisions obviously should have to take into account the patient-related factors (age, performance status, co-morbidities, and symptoms), and tumor features (size, localization, and histological grade)8) 9). Given the high incidence of local recurrence, radiotherapy usually is indicated when surgical access is difficult, poses a high risk of permanent neurological damage, resulting in incomplete resection and the tumors are Grades II or III.

Stereotactic radiosurgery (SRS) and fractionated Stereotactic radiotherapy (SRT) have been used in the treatment of symptomatic CSMs for more than 15 years. However, there are very few publications about the long-term disease-free survival rates and monitorization of the neurological abnormalities, radiological findings, and toxicity 10).

Complications

carotid cavernous fistula developed in a 62-year-old woman during an attempt of embolization. The cause is thought to be perforation by the guide wire during catheterization of the meningohypophyseal trunk at the sharp bend at its origin 11).

Case series

Amelot et al., published the natural history using a prospective series of 53 consecutive patients. The median follow-up duration was 10.2 years (range 2-25 years), from 1990 to 2016.

Patients ranged in age from 30 to 72 years (mean 53 years). The meningiomas were diagnosed by major symptoms (mainly oculomotor nerve palsy and neuralgia experienced in 28 patients), minor symptoms (headache, intermittent diplopia in 15 patients), or incidental findings (10 patients). Simple symptomatic treatment (short courses of corticosteroids and carbamazepine) allowed patients to become asymptomatic in 19 (67.9%) of 28 cases experiencing major symptoms, and for 12 (80%) of 15 patients with initial minor symptoms (p < 0.0001). All patients with incidental findings remained asymptomatic. Forty four (83%) of 53 MCSs did not show any significant growth and 42 (80%) of 53 patients were not symptomatic at the end of follow-up (p < 0.001). The radiographic progression-free survival rates (± SD) at 5, 10, and 20 years were 90% ± 4.2%, 82% ± 5.7%, and 70% ± 10.2%, respectively. Five patients (9.4%) with no evidence of any effect of the initial medical treatment desired additional conventional radiation therapy.

Because of the capricious, unpredictable, and slow growth of MCSs, together with high growth variability from one patient to the next, the symptomatic medical treatment of these tumors is a highly effective method. This series shows that these lesions are naturally, clinically, and radiologically indolent 12).

2016

In 65 patients, Sekhar’s classification, modified Kobayashi grading, and the Karnofsky Performance Scale were used to define tumor extension, tumor removal, and clinical outcomes, respectively.

Preoperative CN dysfunction was evident in 64.6% of patients. CN II deficits were most common. The greatest improvement was seen for CN V deficits, whereas CN II and CN IV deficits showed the smallest degree of recovery. Complete resection was achieved in 41.5% of cases and was not significantly associated with functional CN recovery. Internal carotid artery encasement significantly limited the complete microscopic resection of CSM (p < 0.0001). Overall, 18.5% of patients showed symptomatic recurrence after their initial surgery (mean follow-up 60.8 months [range 3-199 months]). The use of adjuvant stereotactic radiosurgery (SRS) after microsurgery independently decreased the recurrence rate (p = 0.009; OR 0.036; 95% CI 0.003-0.430).

Modified Kobayashi tumor resection (Grades I-IIIB) was possible in 41.5% of patients. CN recovery and tumor control were independent of extent of tumor removal. The combination of resection and adjuvant SRS can achieve excellent tumor control. Furthermore, the use of adjuvant SRS independently decreases the recurrence rates of CSM 13).

2010

Sughrue et al. systematically analyzed the published literature and found more than 3000 patients treated for CSMs. Separate meta-analyses were performed to calculate pooled rates of recurrence and cranial neuropathy after 1) gross-total resection, 2) subtotal resection without adjuvant postoperative radiotherapy or radiosurgery, and 3) stereotactic radiosurgery (SRS) alone. Results were expressed as pooled proportions, and random-effects models were used to incorporate any heterogeneity present to generate a pooled proportion. Individual studies were weighted using the inverse variance method, and 95% CIs for each group were calculated from the pooled proportions.

A total of 2065 nonduplicated patients treated for CSM met inclusion criteria for the analysis. Comparisons of the 95% CIs for recurrence of these 3 cohorts revealed that SRS-treated patients experienced improved rates of recurrence (3.2% [95% CI 1.9-4.5%]) compared with either gross-total resection (11.8% [95% CI 7.4-16.1%]) or subtotal resection alone (11.1% [95% CI 6.6-15.7%]) (p < 0.01). The authors found that the pooled mixed-effects rate of cranial neuropathy was markedly higher in patients undergoing resection (59.6% [95% CI 50.3-67.5%]) than for those undergoing SRS alone (25.7% [95% CI 11.5-38.9%]) (p < 0.05).

Radiosurgery provided improved rates of tumor control compared with surgery alone, regardless of the subjective extent of resection 14).


One hundred and seventeen patients with cavernous sinus meningiomas had LINAC radiosurgery in the period 1993-2007. Six cases were lost and 9 had less than 1 year follow up. The remaining 102 patients were prospectively followed up at 1 y intervals with clinical, neuro-ophthalmological and MRI examinations. Patients’ age ranged between 31 and 86 years (mean 57). Seventy percent were females. The mean tumor volume was 7 cc. Thirty-three patients had previous microsurgery. Tumors were defined with high resolution MRI obtained 1-2 days before treatment and fused to stereotactic CT. Treatment was mostly delivered through a minimultileaf collimator and multiple dynamic arcs. The minimal dose to the tumor margin was 12-17.5 Gy (mean 13.5) encompassed by the 80% isodose shell. Radiation dose to the optic apparatus was kept below 10 Gy. Follow up ranged from 12 to 180 months (mean 67 months). Tumor control (lack of growth) was 98% (58% of the tumors reduced their volumes). Sixty-four patients presented with cranial nerve deficit. Thirty-nine percent improved or resolved following radiosurgery. Cranial neuropathy had significantly higher resolution rates when radiosurgery was performed early (<1 year) after its appearance (53% as opposed to 26%) even in patients with deficits post surgery. Complications were seen in five patients (1 with deafferentation pain, 1 with facial hypesthesia, 1 with visual loss and 2 with partial VI neuropathy). Radiosurgery had a high control rate for meningiomas of the cavernous sinus with few and mild complications. Cranial neuropathy can be solved by treatment, particularly those of recent onset 15).


100 patients (23 male/77 female) with meningiomas involving the cavernous sinus received GKS at the Department of Neurosurgery at Haukeland University Hospital, Bergen, Norway, between November 1988 and July 2006. They were followed for a mean of 82.0 (range, 0-243) months. Only 2 patients were lost to long-term follow-up. Sixty patients underwent craniotomy before radiosurgery, whereas radiosurgery was the primary treatment for 40 patients.

Tumor growth control was achieved in 84.0% of patients. Twelve patients required re-treatment: craniotomy (7), radiosurgery (1), or both (4). Three out of 5 patients with repeated radiosurgery demonstrated secondary tumor growth control. Excluding atypical meningiomas, the growth control rate was 90.4%. The 1-, 5-, and 10-year actuarial tumor growth control rates are 98.9%, 94.2%, and 91.6%, respectively. Treatment failure was preceded by clinical symptoms in 14 of 15 patients. Most tumor growths appeared within 2.5 years. Only one third grew later (range, 6-20 yr). The complication rate was 6.0%: optic neuropathy (2), pituitary dysfunction (3), worsening of diplopia (1), and radiation edema (1). Mortality was 0. At last follow-up, 88.0% were able to live independent lives.

GKS gives long-term growth control and has a low complication rate. Most tumor growths manifest within 3 years following treatment. However, some appear late, emphasizing the need for long-term follow-up 16).

2007

Sindou et al. report on the long-term outcome in 100 consecutive patients with meningiomas arising from the cavernous sinus (CS) with compressive extension outside the CS. The treatment in all cases was surgery alone without adjuvant radiosurgery or radiotherapy. The aim of this study was to evaluate the percentage of patients in whom surgery alone was able to produce long-term tumor control.

All 100 patients harbored meningiomas with supra- and/or laterocavernous extension, and 27 had petroclival extension. Surgery was performed via frontopterionotemporal craniotomy associated with orbital and/or zygomatic osteotomy in 97 patients. Proximal control of the internal carotid artery at the foramen lacerum was undertaken in 65 patients; the paraclinoid carotid segment was exposed extradurally at the space made by the anterior clinoidectomy in 81 patients. For the petroclival tumor extension, a second-stage surgery was performed via a presigmoid-retrolabyrinthine or retrosigmoid approach in 13 and 14 patients, respectively.

The mortality rate was 5% and two patients had severe hemiplegic or aphasic sequelae. The creation or aggravation of disorders in vision, ocular motility, or trigeminal function occurred in 19, 29, and 24% of patients respectively, with a significantly higher rate of complications when resection was performed inside the CS (p < 0.05). Gross-total removal of both the extra- and intracavernous portions was achieved in 12 patients (Group 1), removal of the extracavernous portions with only a partial resection of the intracavernous portion in 28 patients (Group 2), and removal only of the extracavernous portions was performed in 60 patients (Group 3). The follow-up period ranged from 3 to 20 years (mean 8.3 years). There was no tumor recurrence in Group 1. In the 83 surviving patients in Groups 2 and 3 combined, the tumor remnant did not regrow in 72 patients (86.7%); regrowth was noted in 11 (13.3%).

The results suggest that there is no significant oncological benefit in performing surgery within the CS. Because entering the CS entails a significantly higher risk of complications, radiosurgical treatment should be reserved for remnants with secondary growth and clinical manifestations17).

2004

38 consecutive patients with sphenocavernous, clinoidocavernous, and sphenoclinoidocavernous meningiomas who underwent surgical treatment were assessed early and late cranial nerve morbidity, extent of resection, and long-term outcome (mean, 96 mo).

In all patients, tumors exceeded 3 cm diameter. In 22 of 24 patients, total microscopic excision was achieved in tumors that involved only the lateral compartment of the cavernous sinus and touched or partially encased the cavernous internal carotid artery (i.e., modified Hirsch Grades 0 and 1, respectively). In 2 of 24 patients, remaining tumor infiltrated the superior orbital fissure. All 14 patients who had tumors that encased (with or without narrowing) the cavernous segment of the internal carotid artery (Hirsch Grades 2-4) underwent incomplete resection. Among 38 patients, mortality was 0%, late cranial nerve deficits remained in 6 (16%), and late Karnofsky Performance Scale scores exceeded 90 in 34 patients (90%). Four patients (10.5%) developed a recurrence or regrowth. Of 20 patients who were treated with either linear accelerator-based stereotactic radiosurgery or fractionated conformal radiotherapy, 11 had residual tumor and a moderate to high proliferative index, 4 had atypical tumors and 1 had angioblastic meningioma after total excision, 2 had regrowth, and 2 had recurrent tumors. In 18 (90%) of the 20 patients who underwent radiation, tumor size was reduced or controlled.

On the basis of this study and a review of the literature, we demonstrate that sphenocavernous, clinoidocavernous, and sphenoclinoidocavernous meningiomas of Hirsch Grades 0 and 1 can be excised from the lateral compartment of the cavernous sinus without postoperative mortality and with acceptable rates of morbidity. Residual tumor in the medial compartment (Hirsch Grades 2-4) may be treated with some form of radiation therapy or observation 18).

2001

Follow-up periods for the 40 patients ranged from 12 to 123 months (median 42 months), and the overall tumor control rates were 86.4% at 3 years and 82.3% at 10 years. Factors associated with tumor recurrence in univariate analysis were histological malignancy (p < 0.0001), partial treatment (p < 0.0001), suprasellar tumor extension (p = 0.0201), or extension in more than three directions outside the CS (p = 0.0345). When the tumor was completely covered with a dose to the margin that was higher than 14 Gy (Group A, 22 patients), no patient showed recurrence within the median follow-up period of 37 months. On the other hand, when a part of the tumor was treated with 10 to 12 Gy (Group B, 15 patients) or did not receive radiation therapy (Group C, three patients), the recurrence rates were 20% and 100%, respectively. Neurological deterioration was seen in nine patients, but all symptoms were transient or very mild.

The data indicate that stereotactic radiosurgery can control tumor growth if the whole mass can be irradiated by dosages of more than 14 Gy. When optimal radiosurgical planning is not feasible because of a tumor’s large size, irregular shape, or proximity to visual pathways, use of limited surgical resection before radiosurgery is the best option and should provide sufficient long-term tumor control with minimal complications 19).

1996

During the years 1985 to 1992, Knosp et al., encountered 59 patients with meningiomas involving the space of the cavernous sinus. In 29 of these patients, meningiomas were primarily located within the space of the cavernous sinus and were operated on without mortality and with low morbidity. A small subtemporal surgical approach was favored, which allowed initial tumor resection from the posterior aspect, where the Parkinson’s triangle is wide, thus avoiding the additional morbidity of large-scale approaches. According to the relationships of the all-important cranial nerves passing within the lateral wall of the cavernous sinus, we divided the primary intracavernous meningiomas into four types, which reflected not only the preoperative cranial nerve deficit but also the feasibility of surgical resection. Cranial nerve function deteriorated after operations in 14% of oculomotor nerves, in one abducent nerve, in 58% of trochlear nerves, and in 21% of trigeminal nerves. We encountered improvement of function in 43% of oculomotor nerves, in 50% of abducent nerves, and in approximately 30% of the second and third but in only 7% of the first branches of trigeminal nerves. There was no improvement in trochlear nerve function. Improvement of oculomotor nerve function was observed only in moderately impaired nerves, which indicates that surgery should be undertaken early to preserve or improve oculomotor nerve function 20).

1993

Hirsch et al. retrospectively reviewed the CT, MR, and postoperative clinical findings in 65 consecutive patients with pathologically proved cavernous sinus meningiomas who had surgery during the period 1985-1991. Tumors were categorized on the basis of their relationship to the cavernous carotid artery. The presence of tumor in three anatomic sites (the sella, the sphenoid sinus, and the orbital apex) was also correlated with surgical complications.

Category 1 tumors, which do not completely encircle the cavernous carotid artery, were dissected without injury, sacrifice, or grafting of the artery in 91% of cases. Category 2 lesions completely encircle the artery but do not narrow its lumen; they could be dissected from the cavernous carotid artery without arterial injury in 61% of cases, but imaging failed to discriminate differences within this group. Category 3 lesions, which completely encircle and narrow the cavernous carotid artery, are usually difficult to dissect free from the artery. The categories also correlated with recovery of extraocular motility; 84% of category 1 lesions compared with only 36% of category 2 or 3 lesions will recover to good or excellent extraocular motility after cavernous sinus surgery. Tumor involvement of the sella, orbital apex, and sphenoid sinus correlated with postoperative endocrine dysfunction, decreased visual acuity, and CSF leak, respectively.

Imaging studies can frequently predict the difficulty of resecting cavernous sinus meningiomas from the cavernous carotid artery and the likelihood of permanent loss of extraocular motility after surgery on these lesions. This information is helpful in appropriate preoperative planning and in providing information to patients about to undergo such surgery 21).

Case reports

A 33-year-old female patient presented with diplopia and left eye ptosis 26 weeks into her first pregnancy. No investigation was conducted at the time and her symptoms subsided 4 weeks post partum. This same phenomenon occurred during second pregnancy at 20 weeks of gestation, with patient becoming symptom-free again 6 weeks after giving birth. MRI revealed a lesion in the left cavernous sinus in keeping with a meningioma. Due to the surgically challenging location, the lesion was treated with gamma knife radiosurgery. To date, the patient remains asymptomatic with no progression on follow-up imaging 9 years on 22).

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