Cystic craniopharyngioma

Cystic craniopharyngioma

Cystic craniopharyngiomas comprise more than 90% of the craniopharyngiomas.

Treatment

Intracystic treatment options for cystic craniopharyngioma provide data suggestive of durable cyst shrinkage and benefit beyond a pure volume reduction due to repeated fluid aspirations. The effect however is limited to the cystic craniopharyngioma portion without an effect on the solid component. There are multiple challenges relating to technical practicalities: Multicystic occurrence may limit treatment to one cyst only and therefore this approach does not provide the clinical benefit as wished. The thickness of the cyst wall may not allow successful penetration of the scope/catheter into the cyst and different catheter designs make the correct intracystic positioning of the catheter and its holes difficult. Intraoperative ultrasound and computed tomography (CT) have aided to confirm the correct catheter position; however, volume changes during subsequent treatment may influence the intracystic catheter tip location.

Hence the prospect of a minimally invasive intervention – such as an endoscopic insertion of a catheter with a subcutaneous Ommaya reservoir – and subsequent instillation of substances inducing shrinkage of the craniopharyngioma cyst(s), seems a promising strategy 1).

Intracystic bleomycin

A search in electronic databases CENTRAL (2014, Issue 1), MEDLINE/PubMed (from 1966 to March 2014) and EMBASE/Ovid (from 1980 to March 2014) with pre-specified terms, Reference lists of relevant articles and reviews, conference proceedings (International Society for Paediatric Oncology 2005-2013) and ongoing trial databases (Register of the National Institute of Health and International Standard Randomised Controlled Trial Number (ISRCTN) register) in May 2014.

Randomized controlled trials (RCTs), quasi-randomized trials or controlled clinical trials (CCTs) comparing intracystic bleomycin and other treatments for cystic craniopharyngiomas in children (from birth to 18 years).

Two review authors independently performed the data extraction and ‘Risk of bias’ assessment. They used risk ratio (RR) for binary data and mean difference (MD) for continuous data. We planned that if one of the treatment groups experienced no events and there was only one study available for the outcome, we would use the Fischer’s exact test.

Zheng et al. could not identify any studies in which the only difference between the treatment groups was the use of intracystic bleomycin. They did identify a RCT comparing intracystic bleomycin with intracystic phosphorus 32 (n = 7 children). The trial had a high risk of bias. Survival could not be evaluated. There was no evidence of a significant difference between the treatment groups in cyst reduction (MD -0.15, 95% confidence interval (CI) -0.69 to 0.39, P value = 0.59), neurological status (Fisher’s exact P value = 0.429), 3rd nerve paralysis (Fischer’s exact P value = 1.00), fever (RR 2.92, 95% CI 0.73 to 11.70, P value = 0.13) or total adverse effects (RR 1.75, 95% CI 0.68 to 4.53, P value = 0.25). There was a significant difference in favour of the (32)P group for the occurrence of headache and vomiting (Fischer’s exact P value = 0.029 for both outcomes).

Since they identified no RCTs, quasi-randomised trials or CCTs of the treatment of cystic craniopharyngiomas in children in which only the use of intracystic bleomycin differed between the treatment groups, no definitive conclusions could be made about the effects of intracystic bleomycin in these patients. Only one low-power RCT comparing intracystic bleomycin with intracystic (32)P treatment was available, but no definitive conclusions can be made about the effectiveness of these agents in children with cystic craniopharyngiomas. Based on the currently available evidence, we are not able to give recommendations for the use of intracystic bleomycin in the treatment of cystic craniopharyngiomas in children. High-quality RCTs are needed 2).

Phosphorus-32

Radioactive phosphorus 32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR.

Ansari et al reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients’ records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR.

Ansari et al performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors’ institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR.

Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and subsequent treatment was 1.67 ± 1.50 years (mean ± SD).

In this small but focused population, P32 treatment provided limited local control for cyst growth. Brachytherapy alone did not reliably avert the need for subsequent surgery or EBR 3).

Case series

11 non-consecutive adult cystic craniopharyngiomas (7 recurrent lesions) have been treated with Ommaya Reservoir System (ORS), in two neurosurgical centers. ORS was placed in nine cases using minimally invasive procedures: six burr hole endoscopic insertion and three navigated electromagnetic placement; in the remaining two patients, the Ommaya reservoir was used as a shunt to prevent cyst recollection during a transcranial approach.

The main presenting symptoms were visual impairment (75%), cognitive and behavioral disorders (66.7%), hypopituitarism (38%), headache (30.8%) and hypothalamic obesity (8%). The median follow-up period was 41.4 months. In all patients, the visual function and intracranial hypertension improved after decompression. Local tumor control was accomplished in eight patients (72.7%), without the need of adjuvant treatments. The endoscopic vision carried similar rates of tumor control than the stereotaxy (75% vs 66.7%).

In selected patients, tailored procedures are required to achieve long-term tumor control and as well limit surgery-related morbidity. ORS could represent a safe and effective treatment option for cystic craniopharyngiomas, providing also reduced surgical related morbidity especially in recurrent lesions and in patients nonsuitable for radical surgery 4).

References

1)

Bartels U, Laperriere N, Bouffet E, Drake J. Intracystic therapies for cystic craniopharyngioma in childhood. Front Endocrinol (Lausanne). 2012 Mar 27;3:39. doi: 10.3389/fendo.2012.00039. eCollection 2012. PubMed PMID: 22654864; PubMed Central PMCID: PMC3356106.
2)

Zheng J, Fang Y, Cai BW, Zhang H, Liu W, Wu B, Xu JG, You C. Intracystic bleomycin for cystic craniopharyngiomas in children. Cochrane Database Syst Rev. 2014 Sep 19;9:CD008890. doi: 10.1002/14651858.CD008890.pub3. Review. PubMed PMID: 25233847.
3)

Ansari SF, Moore RJ, Boaz JC, Fulkerson DH. Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long-term tumor control in patients with craniopharyngioma. J Neurosurg Pediatr. 2016 Apr;17(4):439-45. doi: 10.3171/2015.8.PEDS15317. Epub 2015 Dec 18. PubMed PMID: 26684761.
4)

Frio F, Solari D, Cavallo LM, Cappabianca P, Raverot G, Jouanneau E. OMMAYA RESERVOIR SYSTEM FOR THE TREATMENT OF CYSTIC CRANIOPHARYNGIOMAS: SURGICAL RESULTS IN A SERIES OF 11 ADULT PATIENTS AND REVIEW OF THE LITERATURE. World Neurosurg. 2019 Aug 7. pii: S1878-8750(19)32133-3. doi: 10.1016/j.wneu.2019.07.217. [Epub ahead of print] PubMed PMID: 31400528.

Craniopharyngioma Cyst Fluid

Craniopharyngioma Cyst Fluid

The dense oily fluid content of craniopharyngioma CPs is reported to cause brain tissue damage, demyelination and axonal loss in the hypothalamus; however, its exact effect on different cell types of CNS is still unexplored.

One cause of postoperative morbidity, and indeed mortality, is aseptic meningitis from spill-out of craniopharyngioma cyst contents.

Halliday and Cudlip from the John Radcliffe Hospital, developed a surgical technique for the management of large craniopharygngioma cysts extending into the third ventricle, to reduce this risk.

They described a technique of using an epidural catheter, inserted into the working channel of a neuroendoscope, to decompress the cystic portion of a craniopharyngioma cyst before opening the cyst wall widely, preventing spill-out of large volumes of cyst content into the ventricular system.

They had no cases of aseptic meningitis, nor any complications, from use of the described technique.

They believe that this is a safe and effective technique of decompression and fenestration of large suprasellar craniopharyngioma cysts that reduces rates of aseptic meningitis and the associated morbidity and mortality from this 1)


In a study, Ghosh et al. from Bangalore, collected CP cyst fluid (CCF) from mostly young patients during surgical removal and exposed it 9-10 days in vitro to the primary cultures derived from rat brain hypothalamus for 48 hours. A gradual decline in cell viability was noted with increasing concentration of CCF. Moreover, a distinct degenerative morphological transformation was observed in neurons and glial cells, including appearance of blebbing and overall reduction of the cell volume. Further, enhanced expression of Caspase-3 in neurons and glial cells exposed to CCF by immunofluorescence imaging, supported by Western blot experiment suggest CCF induced apoptosis of hypothalamic cells in culture.

They demonstrated the deleterious effects of the cyst fluid on various cell types within the tumors originating region of the brain and its surroundings for the first time. Taken together, this finding could be beneficial towards identifying the region specific toxic effects of the cyst fluid and its underlying mechanism 2).


Craniopharyngiomas (CPs) are cystic, encapsulated, slow-growing epithelial tumors. CPs can be aggressive forms invading and resorting surrounding structures of adjacent brain tissue, where Rosenthal fibers (RFs) are expressed. The aim of this study was to investigate the ultrastructure of these fibers in human biopsies and compare it with an experimental toxic model produced by the cortical infusion of the oil cyst fluid (“Oil machinery” fluid or OMF) from CPs to rats. For this purpose, the CPs from ten patients were examined by light and electron microscopy. OMF was administered to rats intracortically. Immunohistochemical detection of glial fibrillary acidic protein (GFAP) and vimentin was assessed. In both freshly obtained CPs and rat brain tissue, the presence of abundant cellular debris, lipid-laden macrophages, reactive gliosis, inflammation and extracellular matrix destruction were seen. Ultrastructural results suggest focal pathological disturbances and an altered microenvironment surrounding the tumor-brain junction, with an enhanced presence of RFs in human tumors. In contrast, in the rat brain different degrees of cellular disorganization with aberrant filament-filament interactions and protein aggregation were seen, although RFs were absent. Our immunohistochemical findings in CPs also revealed an enhanced expression of GFAP and vimentin in RFs at the peripheral, but not at the central (body) level. Through these findings we hypothesize that the continuous OMF release at the CPs boundary may cause tissue alterations, including damaging of the extracellular matrix, and possibly contributing to RFs formation, a condition that was not possible to reproduce in the experimental model. The presence of RFs at the CPs boundary might be considered as a major criterion for the degree of CPs invasiveness to normal tissue. The lack of RFs reactivity in the experimental model reveals that the invasive component of CPs is not present in the OMF, although the fluid per se can exert tissue damage 3).


Fifteen samples of cyst fluid and 14 samples of blood serum were collected from 14 patients with cystic forms of craniopharyngiomas and studied biochemically regarding total protein, albumin, immunoglobulins G and M contents, lactate and pH. Analysis of the data obtained for cyst fluids according to Felgenhauer and comparing them to those obtained for the corresponding blood sera led us to prove the hypothesis of blood-brain barrier impairment in patients with cyst formations in craniopharyngioma.

Arefyeva et al. have also revealed an elevated lactate content and decreased pH in cyst fluids compared with blood sera. Thus the pathogenesis of craniopharyngiomal cyst appears to be much more akin to those described for cysts accompanying other brain tumours than it was believed earlier 4).


A prospective study of cystic fluid in craniopharyngiomas in 10 patients was performed to correlate signal intensity on T1-weighted magnetic resonance (MR) images and biochemical analysis. Within 2 days before surgery, each patient underwent MR imaging before and after administration of gadopentetate dimeglumine. Five patients had cystic fluid lower in signal intensity than white matter, with protein levels less than 9,000 mg/dL (90.00 g/L) and no free methemoglobin. One of the five patients had the highest triglyceride concentration (84 mg/dL [0.95 mmol/L]) of all 10 patients; another of these five had the highest cholesterol concentration of all (270 mg/dL [6.98 mmol/L]). It is concluded that the increased signal intensity of cystic fluid in craniopharyngiomas on T1-weighted MR images can be caused by a protein concentration greater than or equal to 9,000 mg/dL (90.00 g/L), the presence of free methemoglobin, or both. In the ranges of concentrations measured in this study, cholesterol and triglyceride did not increase signal intensity 5).

References

1)

Halliday J, Cudlip S. A new technique of endoscopic decompression of suprasellar craniopharyngioma cyst. Acta Neurochir (Wien). 2019 Aug 4. doi: 10.1007/s00701-019-04024-x. [Epub ahead of print] PubMed PMID: 31377958.
2)

Ghosh M, Das S, Rao KVLN, Pruthi N, Ramesh VJ, Raju TR, Sathyaprabha TN. Effects of Craniopharyngioma Cyst Fluid on Neurons and Glial Cells cultured from rat brain hypothalamus. J Chem Neuroanat. 2018 Oct 16. pii: S0891-0618(18)30086-3. doi: 10.1016/j.jchemneu.2018.10.005. [Epub ahead of print] PubMed PMID: 30339791.
3)

Tena-Suck ML, Morales-Del Ángel AY, Hernández-Campos ME, Fernández-Valverde F, Ortíz-Plata A, Hernández AD, Santamaría A. Ultrastructural characterization of craniopharyngioma at the tumor boundary: A structural comparison with an experimental toxic model using “oil machinery” fluid, with emphasis on Rosenthal fibers. Acta Histochem. 2015 Oct;117(8):696-704. doi: 10.1016/j.acthis.2015.09.006. Epub 2015 Oct 26. PubMed PMID: 26515050.
4)

Arefyeva IA, Semenova JB, Zubairaev MS, Kondrasheva EA, Moshkin AV. Analysis of fluid in craniopharyngioma-related cysts in children: proteins, lactate and pH. Acta Neurochir (Wien). 2002 Jun;144(6):551-4; discussion 554. PubMed PMID: 12111487.
5)

Ahmadi J, Destian S, Apuzzo ML, Segall HD, Zee CS. Cystic fluid in craniopharyngiomas: MR imaging and quantitative analysis. Radiology. 1992 Mar;182(3):783-5. PubMed PMID: 1535894.

Craniopharyngioma endoscopic endonasal approach

Craniopharyngioma endoscopic endonasal approach

The highest priority of current surgical craniopharyngioma treatment is to maximize tumor removal without compromising the patients’ long-term functional outcome. Surgical damage to the hypothalamus may be avoided or at least ameliorated with a precise knowledge regarding the type of adherence for each case.

Endoscopic endonasal approach, has been shown to achieve higher rates of hypothalamic preservation regardless of the degree of involvement by tumor 1) 2).

EES was associated with similar, if not better, extent of resection and significantly less ischemic injury than open surgery. Pseudoaneurysms were only seen in the open surgical group. Weight gain was also less prevalent in the EES cohort and appears be correlated with extent of ischemic injury at time of surgery 3).


Schwartz et al., from the Weill Cornell Brain and Spine Center, compared surgical results for Endoscopic skull base surgery (ESBS) with transcranial surgery (TCS) for several different pathologies over two different time periods (prior to 2012 and 2012-2017) to see how results have evolved over time. Pathologies examined were craniopharyngiomaanterior skull base meningiomaesthesioneuroblastomachordoma, and chondrosarcoma.

ESBS offers clear advantages over TCS for most craniopharyngiomas and chordomas. For well-selected cases of planum sphenoidale and tuberculum sellae meningiomas, ESBS has similar rates of resection with higher rates of visual improvement, and more recent results with lower CSF leaks make the complication rates similar between the two approaches. TCS offers a higher rate of resection with fewer complications for olfactory groove meningiomas. ESBS is preferred for lower-grade esthesioneuroblastomas, but higher-grade tumors often still require a craniofacialapproach. There are few data on chondrosarcomas, but early results show that ESBS appears to offer clear advantages for minimizing morbiditywith similar rates of resection, as long as surgeons are familiar with more complex inferolateral approaches.

ESBS is maturing into a well-established approach that is clearly in the patients’ best interest when applied by experienced surgeons for appropriate pathology. Ongoing critical reevaluation of outcomes is essential for ensuring optimal results 4).

Qiao et al., conducted a systematic review and meta-analysis. They conducted a comprehensive search of PubMed to identify relevant studies. Pituitary, hypothalamus functions and recurrence were used as outcome measures. A total of 39 cohort studies involving 3079 adult patients were included in the comparison. Among these studies, 752 patients across 17 studies underwent endoscopic transsphenoidal resection, and 2327 patients across 23 studies underwent transcranial resection. More patients in the endoscopic group (75.7%) had visual symptoms and endocrine symptoms (60.2%) than did patients in the transcranial group (67.0%, p = 0.038 and 42.0%, p = 0.016). There was no significant difference in hypopituitarism and pan-hypopituitarism after surgery between the two groups: 72.2% and 43.7% of the patients in endoscopic group compared to 80.7% and 48.3% in the transcranial group (p = 0.140 and p = 0.713). We observed same proportions of transient and permanent diabetes insipidusin both groups. Similar recurrence was observed in both groups (p = 0.131). Pooled analysis showed that neither weight gain (p = 0.406) nor memory impairment (p = 0.995) differed between the two groups. Meta-regression analysis revealed that gross total resection contributed to the heterogeneity of recurrence proportion (p < 0.001). They observed similar proportions of endocrine outcomes and recurrence in both endoscopic and transcranial groups. More recurrences were observed in studies with lower proportions of gross total resection 5).


The extended endoscopic transsphenoidal approach has been more recently developed as a potentially surgically aggressive, yet minimal access, alternative.

Komotar et al performed a systematic review of the available published reports after endoscope-assisted endonasal approaches and compared their results with transsphenoidal purely microscope-based or transcranial microscope-based techniques.

The endoscopic endonasal approach is a safe and effective alternative for the treatment of certain craniopharyngiomas. Larger lesions with more lateral extension may be more suitable for an open approach, and further follow-up is needed to assess the long-term efficacy of this minimal access approach 6)

Extended endoscopic transsphenoidal approach have gained interest. Surgeons have advocated for both approaches, and at present there is no consensus whether one approach is superior to the other.

With the widespread use of endoscopes in endonasal surgery, the endoscopic transtuberculum transplanum approach have been proposed as an alternative surgical route for removal of different types of suprasellar tumors, including solid craniopharyngiomas in patients with normal pituitary function and small sella.

As part of a minimally disruptive treatment paradigm, the extended endoscopic transsphenoidal approach has the potential to improve rates of resection, improve postoperative visual recovery, and minimize surgical morbidity 7).

The endoscopic endonasal approach has become a valid surgical technique for the management of craniopharyngiomas. It provides an excellent corridor to infra- and supradiaphragmatic midline craniopharyngiomas, including the management of lesions extending into the third ventricle chamber. Even though indications for this approach are rigorously lesion based, the data confirm its effectiveness in a large patient series 8).

The endoscopic endonasal approach offers advantages in the management of craniopharyngiomas that historically have been approached via the transsphenoidal approach (i.e., purely intrasellar or intra-suprasellar infradiaphragmatic, preferably cystic lesions in patients with panhypopituitarism).

Use of the extended endoscopic endonasal approach overcomes the limits of the transsphenoidal route to the sella enabling the management of different purely suprasellar and retrosellar cystic/solid craniopharyngiomas, regardless of the sellar size or pituitary function 9).

They provide acceptable results comparable to those for traditional craniotomies. Endoscopic endonasal surgery is not limited to adults and actually shows higher resection rates in the pediatric population 10).

Case series

References

1)

Tan TSE, Patel L, Gopal-Kothandapani JS, Ehtisham S, Ikazoboh EC, Hayward R, et al: The neuroendocrine sequelae of paediatric craniopharyngioma: a 40-year meta-data analysis of 185 cases from three UK centres. Eur J Endocrinol 176:359–369, 2017
2)

Yokoi H, Kodama S, Kogashiwa Y, Matsumoto Y, Ohkura Y, Nakagawa T, et al: An endoscopic endonasal approach for early-stage olfactory neuroblastoma: an evaluation of 2 cases with minireview of literature. Case Rep Otolaryngol 2015:541026, 2015
3)

Madsen PJ, Buch VP, Douglas JE, Parasher AK, Lerner DK, Alexander E, Workman AD, Palmer JN, Lang SS, Kennedy BC, Vossough A, Adappa ND, Storm PB. Endoscopic endonasal resection versus open surgery for pediatric craniopharyngioma: comparison of outcomes and complications. J Neurosurg Pediatr. 2019 Jun 7:1-10. doi: 10.3171/2019.4.PEDS18612. [Epub ahead of print] PubMed PMID: 31174192.
4)

Schwartz TH, Morgenstern PF, Anand VK. Lessons learned in the evolution of endoscopic skull base surgery. J Neurosurg. 2019 Feb 1;130(2):337-346. doi: 10.3171/2018.10.JNS182154. Review. PubMed PMID: 30717035.
5)

Qiao N. Endocrine outcomes of endoscopic versus transcranial resection of craniopharyngiomas: A system review and meta-analysis. Clin Neurol Neurosurg. 2018 Apr 7;169:107-115. doi: 10.1016/j.clineuro.2018.04.009. [Epub ahead of print] Review. PubMed PMID: 29655011.
6)

Komotar RJ, Starke RM, Raper DM, Anand VK, Schwartz TH. Endoscopic endonasal compared with microscopic transsphenoidal and open transcranial resection of craniopharyngiomas. World Neurosurg. 2012 Feb;77(2):329-41. doi: 10.1016/j.wneu.2011.07.011. Epub 2011 Nov 1. Review. PubMed PMID: 22501020.
7)

Zacharia BE, Amine M, Anand V, Schwartz TH. Endoscopic Endonasal Management of Craniopharyngioma. Otolaryngol Clin North Am. 2016 Feb;49(1):201-12. doi: 10.1016/j.otc.2015.09.013. Review. PubMed PMID: 26614838.
8)

Cavallo LM, Frank G, Cappabianca P, Solari D, Mazzatenta D, Villa A, Zoli M, D’Enza AI, Esposito F, Pasquini E. The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients. J Neurosurg. 2014 May 2. [Epub ahead of print] PubMed PMID: 24785324.
9)

Cavallo LM, Solari D, Esposito F, Villa A, Minniti G, Cappabianca P. The Role of the Endoscopic Endonasal Route in the Management of Craniopharyngiomas. World Neurosurg. 2014 Dec;82(6S):S32-S40. doi: 10.1016/j.wneu.2014.07.023. Review. PubMed PMID: 25496633.
10)

Koutourousiou M, Gardner PA, Fernandez-Miranda JC, Tyler-Kabara EC, Wang EW, Snyderman CH. Endoscopic endonasal surgery for craniopharyngiomas: surgical outcome in 64 patients. J Neurosurg. 2013 Nov;119(5):1194-207. doi: 10.3171/2013.6.JNS122259. Epub 2013 Aug 2. PubMed PMID: 23909243.
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