Stereotactic radiosurgery for the treatment of a distant recurrence of ependymoma on the optic nerve: illustrative case

Eduardo Orrego González Departments of Neurological Surgery, and

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M. Beatriz Lopes Department of Pathology (Neuropathology), University of Virginia Health, Charlottesville, Virgina

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Gabriel Anibal Ramos Departments of Neurological Surgery, and

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Jason P Sheehan Departments of Neurological Surgery, and

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BACKGROUND

Ependymomas rarely disseminate to other central nervous system areas distant from the original site. Stereotactic radiosurgery (SRS) provides high control rates for recurring ependymomas. The treatment of optic nerve tumors carries high morbidity, but SRS is an acceptable option to manage these cases to reduce risks.

OBSERVATIONS

The authors report the case of a 31-year-old male with a cervical spinal ependymoma who had a disseminated pattern of recurrence including the optic nerve after initial resection of the cervical lesion. The optic nerve tumor was treated with SRS, and the authors discuss the technical aspects of the treatment and its outcomes. At the last follow-up, the optic nerve tumor was controlled with SRS, and visual function was preserved.

LESSONS

High-grade ependymomas such as the one in the presented case can have unpredictable patterns of recurrence. SRS provides excellent control of the distant recurring ependymoma with a low complication profile given the location of the tumor in this case.

ABBREVIATIONS

CNS = central nervous system; CSF = cerebrospinal fluid; GKRS = Gamma Knife radiosurgery; IDEM = intradural extramedullary; MRI = magnetic resonance imaging; SRS = stereotactic radiosurgery; WHO = World Health Organization

BACKGROUND

Ependymomas rarely disseminate to other central nervous system areas distant from the original site. Stereotactic radiosurgery (SRS) provides high control rates for recurring ependymomas. The treatment of optic nerve tumors carries high morbidity, but SRS is an acceptable option to manage these cases to reduce risks.

OBSERVATIONS

The authors report the case of a 31-year-old male with a cervical spinal ependymoma who had a disseminated pattern of recurrence including the optic nerve after initial resection of the cervical lesion. The optic nerve tumor was treated with SRS, and the authors discuss the technical aspects of the treatment and its outcomes. At the last follow-up, the optic nerve tumor was controlled with SRS, and visual function was preserved.

LESSONS

High-grade ependymomas such as the one in the presented case can have unpredictable patterns of recurrence. SRS provides excellent control of the distant recurring ependymoma with a low complication profile given the location of the tumor in this case.

ABBREVIATIONS

CNS = central nervous system; CSF = cerebrospinal fluid; GKRS = Gamma Knife radiosurgery; IDEM = intradural extramedullary; MRI = magnetic resonance imaging; SRS = stereotactic radiosurgery; WHO = World Health Organization

Ependymal tumors are currently classified by the World Health Organization (WHO) according to anatomical location, histopathological features, and molecular profiling.1,2 The updated WHO classification subcategorizes ependymomas of the spinal compartment with further distinction depending on molecular features.1,2 These lesions are central nervous system (CNS) tumors WHO grade 3. They were previously called “anaplastic ependymoma” and are characterized by their aggressive nature and poor prognosis.1,3 These tumors predominantly originate from the ependymal cells lining the spinal cord’s ventricular system and central canal.3 The incidence of anaplastic ependymoma is higher in age groups 0 to 4 years, with 0.43 cases per 100,000, compared to all other age groups.4

Spinal ependymoma seldom recurs in distant CNS regions after dissemination through the neuroaxis.4,5 The optic nerve and orbit are occasionally affected by CNS neoplasms, most commonly meningiomas and gliomas in the background of genetic syndromes such as neurofibromatosis type 1.6,7

Ependymomas are resected, and some cases benefit from adjuvant therapies such as radiosurgery and chemotherapy.4,6,7 Stereotactic radiosurgery (SRS) is an alternative to resection for a tumor location that has an increased risk of neurological complications or for recurring and progressing tumors.8 We aim to describe the clinical presentation, diagnostic workup, and SRS treatment of a recurring ependymoma with distant dissemination to the optic nerve and orbit.

Illustrative Case

A 31-year-old male presented with a complex medical history of anaplastic ependymoma WHO grade 3. Initially, he presented with radiculopathy, weakness of the left limbs, and bladder dysfunction. Cervical magnetic resonance imaging (MRI) showed a lesion in the C4 to C7 area, and resection of the spinal tumor was performed, followed by fractionated radiation therapy (Fig. 1). Histopathological examination of the resected mass revealed a glial neoplasm characterized by fibrillary glial cells with numerous perivascular pseudorosettes. In focal areas, the tumor showed nodules of hypercellularity, numerous mitotic figures, and microvascular proliferation, features consistent with a higher-grade ependymoma (Fig. 2). At the time of the surgery, the diagnosis of anaplastic ependymoma, WHO grade 3 was made according to the 2007 WHO classification. According to the current WHO classification,2 the tumor corresponds to spinal ependymoma, WHO grade 3, not otherwise specified. Despite this surgery, the patient experienced recurrent disease in the thoracic level 6 years later, and a second surgery was performed for resection of this new lesion (Fig. 3).

FIG. 1
FIG. 1

Presurgical MRI. A: Sagittal T1-weighted sequence. B: Sagittal postcontrast T1-weighted sequence. C: Sagittal T2-weighted sequence. D: Axial postcontrast T1-weighted sequence. The intradural-extramedullary mass measured 09 × 1.7 × 4.3 mm, extending from the C4–5 disc space to the upper C7 vertebral body level.

FIG. 2
FIG. 2

Histopathological findings of the tumor. Moderately cellular glial neoplasm (A) composed of fibrillary cells with perivascular arrangements consistent with pseudorosettes (B). In focal hypercellular areas of the tumor, numerous mitotic figures were present (C, arrows). The tumor cells were strongly and diffusely GFAP-immunoreactive (D) and showed intracytoplasmic dot-like EMA immunoreactivity (E). The Ki-67 labeling index (MIB-1) was very high (F, about 40%) in the hypercellular areas of the ependymoma. Hematoxylin and eosin (A–C), original magnifications ×100 (A and D), ×200 (B, F), and ×400 (C and E).

FIG. 3
FIG. 3

Follow-up MRI. A: Sagittal postcontrast T1-weighted sequence at 6 years showing a new hyperintense lesion on the T10–11 level, extending through the upper level of T11. B: Axial T2-weighted sequence. C: Sagittal T2-weighted sequence from the last MRI follow-up. D: Axial postcontrast T1-weighted sequence showing a left cerebellar hyperintense heterogeneously enhancing lesion. E: Axial T1-weighted sequence showing an isointense cerebellar lesion.

The patient had marked decreased visual acuity (20/80) and superior temporal quadrantanopia of the left eye 2 years after this second spinal tumor resection. Brain MRI was performed, and a hyperintense lesion of the optic nerve was found (Fig. 4A–C).

FIG. 4
FIG. 4

Axial T1-weighted MRI sequence (A), postcontrast T1-weighted MRI sequence (B), postcontrast T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI sequence (C) showing a hyperintense lesion of 22 × 6 mm on the left posterior intraorbital and intracanalicular portions of the optic nerve. Three-year follow-up T2-weighted FLAIR MRI (D) that shows control of the tumor.

Progression of the disease prompted treatment with systemic therapy combined with Gamma Knife Radiosurgery (GKRS) to control the tumor involving the optic nerve and preserve vision. For systemic therapy, the patient was started on bevacizumab at a dose of 7.5 mg/kg every 3 weeks and radiation therapy to the spinal lesions.

SRS was delivered over five fractions using a dose of 4.5 Gy per fraction to a volume of 1.56 cm3. The plan was carefully designed to minimize radiation exposure to critical structures, including the right optic nerve. Postradiosurgery, the lesion on the left optic nerve was stable at the last follow-up, 3 years after SRS treatment (Fig. 4D). On this last clinical follow-up, visual acuity was preserved as compared to before SRS. Motor strength and bladder function were also normal.

Despite the different treatments, the spinal lesions continued to progress, and a new tumor developed on the left inferior cerebellum (Fig. 3). This lesion received fractioned SRS over five sessions, receiving a dose of 30 Gy. This lesion was recently treated and has no follow-up currently.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

Ependymomas are the most common tumors of the cervical spine (40%–60%), constitute 30% to 40% of all intramedullary tumors, and are the most common intramedullary tumor.1,9 MRI usually depicts a contrast-enhancing lesion with syrinx formation.10 In our case, the patient presented with a cervical intradural extramedullary (IDEM), lesion that prompted an initial diagnosis of meningioma. IDEM ependymomas are most common at the filum terminale as myxopapillary ependymomas, but cervical lesions such as the one in our patient have been reported previously.11 In addition, pathological examination confirmed that the lesion was a spinal ependymoma (Fig. 2).

Spinal ependymomas usually have an excellent prognosis when total resection is achieved, and recurrence is unlikely.12 Survival ranges are high at 5 years (85%–100%).12 In our case, we believe that the aberrant and malignant pattern of dissemination could be due to an initial subtotal resection of the cervical lesion and the aggressive pathophysiology of a grade III ependymoma. A full molecular profile was lacking to classify the tumor with an N-MYC mutation, which confers a more aggressive pattern to these tumors with wide dissemination in the CNS and atypical radiological images.13

Ependymomas can migrate to distant locations either within the CNS or to extraneural tissue (e.g., lungs, lymph nodes).3,14 Authors have proposed several explanations for this phenomenon, including an aberrant communication between extradural and intradural spaces, surgical manipulation of tissue, and movement through the cerebrospinal fluid (CSF) to other areas of CNS or systemic circulation. In the case of spinal ependymomas, these can disseminate through CSF to intracranial locations covered by meningeal layers.5,6 Initial surgical manipulation of the tumor and CSF migration explain the disseminated disease in our patient, including disease spread to the optic nerve and cerebellum. A previous case by Awaya et al.6 depicted a myxopapillary ependymoma with wide dissemination throughout the CNS. The authors discussed the possibility of this subtype of ependymoma having these patterns of dissemination.

SRS is an alternative for recurrent cases after initial resection.8,15 It provides good tumor control and improved survival at follow-up.8,15 Progression-free survival after undergoing GKRS for recurring anaplastic ependymomas has been reported to be 81.6% at 1 year with low toxicity rates.8,15–17 Optic nerve lesions are sensitive to all treatment modalities and carry high-risk complications after treatment.18 In the case of optic nerve meningiomas, microsurgical techniques produce vision loss at a high rate in patients.18 SRS achieves a high rate of control and often the stability of visual fields and visual acuity (90%).18

Our case presents an uncommon pattern of distant dissemination for a spinal ependymoma. In such cases, resection can afford tissue diagnosis and relief of mass effect. However, given the multifocal nature of disseminated anaplastic ependymoma, other treatments beyond resection are frequently needed. In the intracranial space, SRS in a single or hypofractionated approach can be utilized for small-volume anaplastic ependymomas. For larger-volume tumors or tumors situated near more radiation-sensitive critical structures (e.g., cervical spine), fractionated radiation therapy with photons or protons can be employed, as in the current case. GKRS was used to treat a distant recurring intracranial ependymoma as the primary management because of the high risk of visual impairment. The lesion was controlled at the follow-up, and visual outcomes were preserved. Thus, GKRS can be an excellent therapeutic choice for recurrent ependymomas. In this case, the lesion was abutting the optic nerve, which made resection less preferred.

Lessons

This is the case of an ependymoma with atypical imaging, disseminated disease, and distant recurrence on the optic nerve. The molecular profile of the tumor and the nature of the ependymomas could explain the uncommon pattern of tumor spreading in this patient. Our findings contribute to the literature on SRS for optic nerve lesions and recurring ependymoma. SRS can be an effective treatment for this type of tumor in this location. Tumors in immediate proximity to the optic nerve can be treated using SRS to preserve visual function with results similar to those of more common tumors (meningioma).

In this report, we present the case of a 45-year-old male with a spinal ependymoma with disseminated disease and recurrence involving the left optic nerve. The molecular profile of the tumor and the nature of the ependymomas could explain the uncommon pattern of tumor spreading in this patient. Surgical management of optic nerve lesions poses significant risks to visual function. GKRS achieved control of the optic tumor, and the visual function was preserved after radiosurgery.

Author Contributions

Conception and design: Sheehan, Orrego González, Ramos. Acquisition of data: Orrego González, Lopes. Analysis and interpretation of data: all authors. Drafting the article: all authors. Critically revising the article: all authors. Reviewed submitted version of manuscript: Sheehan, Orrego González, Lopes. Approved the final version of the manuscript on behalf of all authors: Sheehan. Statistical analysis: Orrego González. Study supervision: Sheehan.

References

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    Weller M, van den Bent M, Hopkins K, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014;15(9):e395e403.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):12311251.

  • 3

    Alzahrani A, Alassiri A, Kashgari A, Alrehaili J, Alshaalan H, Zakzouk R Extraneural metastasis of an ependymoma: a rare occurrence. Neuroradiol J. 2014;27(2):175178.

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  • 4

    Achey RL, Vo S, Cioffi G, et al. Ependymoma, NOS and anaplastic ependymoma incidence and survival in the United States varies widely by patient and clinical characteristics, 2000–2016. Neurooncol Pract. 2020;7(5):549558.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Pencovich N, Bot G, Lidar Z, et al. Spinal ependymoma with regional metastasis at presentation. Acta Neurochir (Wien). 2014;156(6):12151222.

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    Awaya T, Nishimura Y, Eguchi K, et al. Preoperative intracranial dissemination of spinal myxopapillary ependymoma attributed to tumor hemorrhage. World Neurosurg. 2021;145:1318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Huang M, Patel J, Patel BC Optic Nerve Glioma. In: StatPearls. StatPearls Publishing; 2023. Accessed October 5, 2023. http://www.ncbi.nlm.nih.gov/books/NBK557878/

    • PubMed
    • Export Citation
  • 8

    Kano H, Niranjan A, Kondziolka D, Flickinger JC, Lunsford LD Outcome predictors for intracranial ependymoma radiosurgery. Neurosurgery. 2009;64(2):279288.

  • 9

    Alhalabi OT, Heene S, Landré V, et al. Association of early surgery and absence of ataxia with full recovery after spinal intramedullary ependymoma resection. J Neurosurg Spine. Published online November 3, 2023. doi: 10.3171/2023.8.SPINE23606.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Koeller KK, Rosenblum RS, Morrison AL Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation. Radiogaphics. 2000;20(6):17211749.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Morselli C, Ruggeri AG, Pichierri A, et al. Intradural extramedullary primary ependymoma of the craniocervical junction combined with C1 partial agenesis: case report and review of the literature. World Neurosurg. 2015;84(6):2076e1-6.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Chanbor H, Kelly PD, Topf MC, et al. Resection of a ventral intramedullary spinal cord ependymoma through an anterior cervical approach: illustrative case. J Neurosurg Case Lessons. 2023;6(1):CASE23243.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Ghasemi DR, Sill M, Okonechnikov K, et al. MYCN amplification drives an aggressive form of spinal ependymoma. Acta Neuropathol. 2019;138(6):10751089.

  • 14

    Umbach G, El Ahmadieh TY, Plitt AR, et al. Extraneural metastatic anaplastic ependymoma: a systematic review and a report of metastases to bilateral parotid glands. Neurooncol Pract. 2020;7(2):218227.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Shi S, Jin MC, Koenig J, et al. Stereotactic radiosurgery for pediatric and adult intracranial and spinal ependymomas. Stereotact Funct Neurosurg. 2019;97(3):189194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Kano H, Su YH, Wu HM, et al. Stereotactic radiosurgery for intracranial ependymomas: an international multicenter study. Neurosurgery. 2019;84(1):227234.

  • 17

    Stauder MC, Ni Laack N, Ahmed KA, Link MJ, Schomberg PJ, Pollock BE Stereotactic radiosurgery for patients with recurrent intracranial ependymomas. J Neurooncol. 2012;108(3):507512.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Vaishnav YJ, Singh R, Didwania P, et al. Radiotherapy and radiosurgery in the management of optic nerve sheath meningiomas: an international systematic review and meta-analysis of twenty Studies. World Neurosurg. 2022;164:e929e944.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Collapse
  • Expand
  • FIG. 1

    Presurgical MRI. A: Sagittal T1-weighted sequence. B: Sagittal postcontrast T1-weighted sequence. C: Sagittal T2-weighted sequence. D: Axial postcontrast T1-weighted sequence. The intradural-extramedullary mass measured 09 × 1.7 × 4.3 mm, extending from the C4–5 disc space to the upper C7 vertebral body level.

  • FIG. 2

    Histopathological findings of the tumor. Moderately cellular glial neoplasm (A) composed of fibrillary cells with perivascular arrangements consistent with pseudorosettes (B). In focal hypercellular areas of the tumor, numerous mitotic figures were present (C, arrows). The tumor cells were strongly and diffusely GFAP-immunoreactive (D) and showed intracytoplasmic dot-like EMA immunoreactivity (E). The Ki-67 labeling index (MIB-1) was very high (F, about 40%) in the hypercellular areas of the ependymoma. Hematoxylin and eosin (A–C), original magnifications ×100 (A and D), ×200 (B, F), and ×400 (C and E).

  • FIG. 3

    Follow-up MRI. A: Sagittal postcontrast T1-weighted sequence at 6 years showing a new hyperintense lesion on the T10–11 level, extending through the upper level of T11. B: Axial T2-weighted sequence. C: Sagittal T2-weighted sequence from the last MRI follow-up. D: Axial postcontrast T1-weighted sequence showing a left cerebellar hyperintense heterogeneously enhancing lesion. E: Axial T1-weighted sequence showing an isointense cerebellar lesion.

  • FIG. 4

    Axial T1-weighted MRI sequence (A), postcontrast T1-weighted MRI sequence (B), postcontrast T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI sequence (C) showing a hyperintense lesion of 22 × 6 mm on the left posterior intraorbital and intracanalicular portions of the optic nerve. Three-year follow-up T2-weighted FLAIR MRI (D) that shows control of the tumor.

  • 1

    Weller M, van den Bent M, Hopkins K, et al. EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol. 2014;15(9):e395e403.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):12311251.

  • 3

    Alzahrani A, Alassiri A, Kashgari A, Alrehaili J, Alshaalan H, Zakzouk R Extraneural metastasis of an ependymoma: a rare occurrence. Neuroradiol J. 2014;27(2):175178.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Achey RL, Vo S, Cioffi G, et al. Ependymoma, NOS and anaplastic ependymoma incidence and survival in the United States varies widely by patient and clinical characteristics, 2000–2016. Neurooncol Pract. 2020;7(5):549558.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Pencovich N, Bot G, Lidar Z, et al. Spinal ependymoma with regional metastasis at presentation. Acta Neurochir (Wien). 2014;156(6):12151222.

  • 6

    Awaya T, Nishimura Y, Eguchi K, et al. Preoperative intracranial dissemination of spinal myxopapillary ependymoma attributed to tumor hemorrhage. World Neurosurg. 2021;145:1318.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Huang M, Patel J, Patel BC Optic Nerve Glioma. In: StatPearls. StatPearls Publishing; 2023. Accessed October 5, 2023. http://www.ncbi.nlm.nih.gov/books/NBK557878/

    • PubMed
    • Export Citation
  • 8

    Kano H, Niranjan A, Kondziolka D, Flickinger JC, Lunsford LD Outcome predictors for intracranial ependymoma radiosurgery. Neurosurgery. 2009;64(2):279288.

  • 9

    Alhalabi OT, Heene S, Landré V, et al. Association of early surgery and absence of ataxia with full recovery after spinal intramedullary ependymoma resection. J Neurosurg Spine. Published online November 3, 2023. doi: 10.3171/2023.8.SPINE23606.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Koeller KK, Rosenblum RS, Morrison AL Neoplasms of the spinal cord and filum terminale: radiologic-pathologic correlation. Radiogaphics. 2000;20(6):17211749.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Morselli C, Ruggeri AG, Pichierri A, et al. Intradural extramedullary primary ependymoma of the craniocervical junction combined with C1 partial agenesis: case report and review of the literature. World Neurosurg. 2015;84(6):2076e1-6.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Chanbor H, Kelly PD, Topf MC, et al. Resection of a ventral intramedullary spinal cord ependymoma through an anterior cervical approach: illustrative case. J Neurosurg Case Lessons. 2023;6(1):CASE23243.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Ghasemi DR, Sill M, Okonechnikov K, et al. MYCN amplification drives an aggressive form of spinal ependymoma. Acta Neuropathol. 2019;138(6):10751089.

  • 14

    Umbach G, El Ahmadieh TY, Plitt AR, et al. Extraneural metastatic anaplastic ependymoma: a systematic review and a report of metastases to bilateral parotid glands. Neurooncol Pract. 2020;7(2):218227.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Shi S, Jin MC, Koenig J, et al. Stereotactic radiosurgery for pediatric and adult intracranial and spinal ependymomas. Stereotact Funct Neurosurg. 2019;97(3):189194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Kano H, Su YH, Wu HM, et al. Stereotactic radiosurgery for intracranial ependymomas: an international multicenter study. Neurosurgery. 2019;84(1):227234.

  • 17

    Stauder MC, Ni Laack N, Ahmed KA, Link MJ, Schomberg PJ, Pollock BE Stereotactic radiosurgery for patients with recurrent intracranial ependymomas. J Neurooncol. 2012;108(3):507512.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Vaishnav YJ, Singh R, Didwania P, et al. Radiotherapy and radiosurgery in the management of optic nerve sheath meningiomas: an international systematic review and meta-analysis of twenty Studies. World Neurosurg. 2022;164:e929e944.

    • PubMed
    • Search Google Scholar
    • Export Citation

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