Extraforaminal Microdiscectomy for Upper Lumbar Disc Herniations: A Minimally Invasive Alternative Surgical Approach.

BACKGROUND: Various methods and techniques have been developed for extraforaminal decompression, particularly for far lateral lumbar disc herniation. Distinct anatomical differences are noticeable in the upper levels of the lumbar spine, which may complicate the related surgical approach. This study aimed to determine the safety and efficiency of the far lateral extraforaminal approach for the upper lumbar disc. METHODS: L1-2 and L2-3 migrated lumbar disc herniations were defined as upper lumbar disc herniations. 31 consecutive patients with upper lumbar disk herniation who underwent extraforaminal lumbar microdiscectomy between January 2018 and March 2022 were retrospectively investigated. The patients were assessed using the interval history, follow-up lower back and leg pain visual analog scale scores (0-100 mm), the Oswestry Disability Index (%), and modified MacNab criteria. RESULTS: 31 consecutive patients with upper lumbar disk herniation (20 men and 11 women) with a mean age of 52.8 ± 10.8 years (range 31-70 years) underwent extraforaminal lumbar microdiscectomy. The preoperative and postoperative visual analog scale scores and Oswestry Disability Index were significantly different (P < 0.001). According to the modified MacNab criteria, 23 patients showed excellent improvement, 5 showed good improvement, and 3 showed fair improvement; thus, the rate of satisfactory improvement was 90.3% at the 2-year follow-up. No patients required reoperation at the operative level during follow-up. CONCLUSIONS: Extraforaminal lumbar microdiscectomy is a safe and effective minimally invasive surgical technique for treating upper lumbar disc herniation.

An unusual case of pediatric cervical myelopathy due to congenital spinal canal stenosis.

Cervical myelopathy is a condition that is rarely reported in pediatric patients who have movement or neuromuscular disorders. We, herein, present a rare case of cervical myelopathy observed in a 14-year-old patient, who was previously a healthy boy treated with cervical laminoplasty, which was caused by cervical spinal canal stenosis based on multiple level disc herniation. The patient presented to the clinic with spastic and ataxic gait with previous diagnostic challenges. Magnetic resonance imaging showed cervical degenerative changes mainly marked at the C3-C4 and C4-C5 levels, along with canal narrowing and a central high signal cord abnormality on T2-weighted images. A C3-C4 open-door laminoplasty surgery technique was performed. The neurological symptoms and signs improved dramatically following surgery. Subsequently, cervical computed tomography and magnetic resonance imaging showed good decompression of the cervical spinal cord during the 5 years of follow-up with the preservation of the range of movement. We concluded that though it is pretty rare, cervical myelopathy should be considered in diagnosing adolescent patients with gait and balance disorders.

Salvage posterior atlantoaxial fixation techniques: A retrospective study.

OBJECT: Since the atlantoaxial region have critical neurovascular anatomy and limited bone surface for fusion, the application and choice of salvage fixation techniques are highly important. To discuss alternative posterior atlantoaxial fixation surgery techniques. METHODS: We retrospectively surgical records of 22 patients that posterior atlantoaxial fixation techniques were applied. RESULTS: The patients included 11 males and 11 females (mean age: 65.7 years). The fracture type that caused instability is type 2 odontoid fractures (22). In six of these patients alternative stabilization techniques were applied due to anatomical variations, huge venous bleeding and iatrogenic trauma of the screw entry points during surgery. CONCLUSIONS: Owing to anatomical variations, intraoperative challenges, and/or instrumentation failures, performing alternative surgical fixation technique is an important factor that affects the success of stabilization of the atlantoaxial region. Knowledge of salvage techniques especially during the learning curve is vitally important. Surgeons should adapt to intraoperative surgical challenges as required.

Posterior realignment of basilar invagination with facet joint distraction technique.

PURPOSE: We describe our experience with management of basilar invagination (BI) with the atlantoaxial dislocation (C1/C2) joint reduction technique, including posterior atlantoaxial internal fixation. MATERIALS AND METHODS: From 2008 to 2018, eleven patients with atlantoaxial dislocation (AAD) and BI underwent surgical reduction using C1/C2 the joint reduction technique with a fibular graft/peek cage placement followed by C1 lateral mass/C2 pedicle screw fixation. In two cases that we originally planned to perform C1/C2 joint reduction, occiput-C2 pedicle screw fixation was performed instead due to intraoperative challenges. Post-operative course and surgical complications will be discussed. RESULTS: A total of 13 patients, with an average age of 30.46 ± 13.23 years (range 12-57), were operated. In one patient, iatrogenic vertebral artery injury occurred without any neurological complication. JOA score improved from 10.45 ± 1.128 to 15.0 ± 1.949 (p < 0.0001, paired t-test). All radiological indices were improved (p at least < 0.001). No construct failure was seen in any of the patients with C1-2 facet joint distraction technique during follow-up, and no additional anterior decompression surgery was required. CONCLUSIONS: C1/C2 joint reduction technique with fibular graft/cervical PEEK cage of BI patients together with AAD seems to be an effective and safe surgical method of treatment.

What is the restorative effect of VEGF inhibitor bevacuzimab against subarachnoid hemorrhage in an experimental model?

BACKGROUND: This study investigated the effect of vascular endothelial growth factor (VEGF) inhibitor bevacuzimab (BVZ) on the rabbit basilar artery using an experimental subarachnoid hemorrhage (SAH) model. METHODS: Eighteen adult male New-Zealand white rabbits were randomly divided into three groups: a control group (n = 6), SAH group (n = 6), and SAH+BVZ group (n = 6). Experimental SAH was created by injecting autologous arterial blood into the cisterna magna. In the treatment group, the subjects were administered a daily dose of 10 mg/kg, intravenous BVZ for 2 days after the SAH. Basilar artery diameters were measured with magnetic resonance angiography (MRA) 72 h after the SAH in all groups. After 72 h, whole brains, including the upper cervical region, were obtained from all the animals after perfusion and fixation of the animal. The wall thickness, luminal area, and the apoptosis at the basilar arteries were evaluated in all groups. RESULTS: BVZ significantly prevented SAH-induced vasospasm confirmed in vivo with MRA imaging with additional suppression of apoptosis on basilar artery wall. DISCUSSION: VEGF inhibition with BVZ has shown to have a vasospasm and apoptosis attenuating effect on basilar artery in a SAH model.

Neuroprotective Effects of Pregabalin Against Spinal Cord Ischemia-Reperfusion Injury in Rats.

AIM: To evaluate the effect of pregabalin pre-treatment on spinal cord ischemia-reperfusion (I/R) injury and compare with methylprednisolone (MP). MATERIAL AND METHODS: Thirty-two rats were randomly divided into four groups as follow: Group 1 (sham)(n=8), group 2 (ischemia only)(n=8), group 3 (30 mg/kg pregabalin)(n=8), and group 4 (30 mg/kg methylprednisolone)(n=8). Laparotomy was performed without aortic clamp in the sham group. All animals were sacrificed 24 hours after surgery. The spinal cord tissue samples were harvested and caspase-3 activity, tumor necrosis factor-alpha (TNF-α) and Interleukin-1 Beta (IL-1ß) levels, catalase (CAT) activity, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) levels malondialdehyde (MDA) levels and nitric oxide (NO) levels were analyzed to investigate the effects of different excitatory and inflammatory pathways in mechanism of I/R injury. Ultrastructural and histopathological examinations were carried out. Neurological recovery was measured by Basso, Beattie, Bresnahan (BBB) test and Inclined Plane Test. RESULTS: Decresead caspase-3 activity and decreased inflammatory markers like TNF-α, IL-1ß, and decresaed excitotatory pathways like CAT, GPx, MDA, NO and SOD were observed in both pregabalin pre-treatment and MP treatment groups. Pregabalin pre-treatment produced better ultrastructural results compared to MP treatment, as with histopathological examination. Pregabalin group showed better recovery compared to MP treament group according to BBB scoring system. CONCLUSION: Pregabalin pre-treatmet and MP treatment both has neuroprotective effect on I/R injury by decreasing caspase dependant apoptosis, and inflammatory and oxidative stress markers. In addition, pregabalin pre-treatment had better clinical effects compared to MP treatment.

Gene-Silencing Screen for Mammalian Axon Regeneration Identifies Inpp5f (Sac2) as an Endogenous Suppressor of Repair after Spinal Cord Injury.

Axonal growth and neuronal rewiring facilitate functional recovery after spinal cord injury. Known interventions that promote neural repair remain limited in their functional efficacy. To understand genetic determinants of mammalian CNS axon regeneration, we completed an unbiased RNAi gene-silencing screen across most phosphatases in the genome. We identified one known and 17 previously unknown phosphatase suppressors of injury-induced CNS axon growth. Silencing Inpp5f (Sac2) leads to robust enhancement of axon regeneration and growth cone reformation. Results from cultured Inpp5f(-/-) neurons confirm lentiviral shRNA results from the screen. Consistent with the nonoverlapping substrate specificity between Inpp5f and PTEN, rapamycin does not block enhanced regeneration in Inpp5f(-/-) neurons, implicating mechanisms independent of the PI3K/AKT/mTOR pathway. Inpp5f(-/-) mice develop normally, but show enhanced anatomical and functional recovery after mid-thoracic dorsal hemisection injury. More serotonergic axons sprout and/or regenerate caudal to the lesion level, and greater numbers of corticospinal tract axons sprout rostral to the lesion. Functionally, Inpp5f-null mice exhibit enhanced recovery of motor functions in both open-field and rotarod tests. This study demonstrates the potential of an unbiased high-throughput functional screen to identify endogenous suppressors of CNS axon growth after injury, and reveals Inpp5f (Sac2) as a novel suppressor of CNS axon repair after spinal cord injury. Significance statement: The extent of axon regeneration is a critical determinant of neurological recovery from injury, and is extremely limited in the adult mammalian CNS. We describe an unbiased gene-silencing screen that uncovered novel molecules suppressing axonal regeneration. Inpp5f (Sac2) gene deletion promoted recovery from spinal cord injury with no side effects. The mechanism of action is distinct from another lipid phosphatase implicated in regeneration, PTEN. This opens new pathways for investigation in spinal cord injury research. Furthermore the screening methodology can be applied on a genome wide scale to discovery the entire set of mammalian genes contributing to axonal regeneration.

Genetic ablation and short-duration inhibition of lipoxygenase results in increased macroautophagy.

12/15-lipoxygenase (12/15-LOX) is involved in organelle homeostasis by degrading mitochondria in maturing red blood cells and by eliminating excess peroxisomes in liver. Furthermore, 12/15-LOX contributes to diseases by exacerbating oxidative stress-related injury, notably in stroke. Nonetheless, it is unclear what the consequences are of abolishing 12/15-LOX activity. Mice in which the alox15 gene has been ablated do not show an obvious phenotype, and LOX enzyme inhibition is not overtly detrimental. We show here that liver histology is also unremarkable. However, electron microscopy demonstrated that 12/15-LOX knockout surprisingly leads to increased macroautophagy in the liver. Not only macroautophagy but also mitophagy and pexophagy were increased in hepatocytes, which otherwise showed unaltered fine structure and organelle morphology. These findings were substantiated by immunofluorescence showing significantly increased number of LC3 puncta and by Western blotting demonstrating a significant increase for LC3-II protein in both liver and brain homogenates of 12/15-LOX knockout mice. Inhibition of 12/15-LOX activity by treatment with four structurally different inhibitors had similar effects in cultured HepG2 hepatoma cells and SH-SY5Y neuroblastoma cells with significantly increased autophagy discernable already after 2 hours. Hence, our study reveals a link between ablation or inhibition of 12/15-LOX and stimulation of macroautophagy. The enhanced macroautophagy may be related to the known tissue-protective effects of LOX ablation or inhibition under various diseased conditions caused by oxidative stress and ischemia. This could provide an important cleaning mechanism of cells and tissues to prevent accumulation of damaged mitochondria and other cellular components.

Myelopathy and Quadriparesis due to Spinal Cord Compression of C1 Laminar Osteochondroma.

The aim of this paper is to show that osteochondromas of the cervical vertebrae can cause myelopathy and neck pain.The reported etiology, diagnosis, treatment and differential diagnosis were reviewed. Osteochondromas may present as a solitary lesion with no genetic component or as multiple lesions as a part of a genetic disorder known as hereditary multiple exostosis. Osteochondromas of the spine are rarely encountered in clinical practice. These lesions are reported more commonly with neural compression in cases associated with hereditary multiple exostosis. The authors describe a unusual clinical manifestation of a solitary osteochondroma located in the right posterior arch of the atlas. Complete removal of the tumor was performed resulting in the relief of neck pain and spastic quadriparesis. Although unusual, osteochondromas of the cervical spine must be considered in patients with persistent neck pain and progressive symptoms of myelopathy. Computed tomography and magnetic resonance imaging in conjunction with plain radiograms is the neuroradiological modality of choice. The diagnosis and surgical excision of these tumors are important because they can cause spinal stenosis resulting in neural tissue compression and myelopathy.

Freehand C1 lateral mass screw fixation technique: our experience.

BACKGROUND: Although C1 lateral mass fixation technique is frequently performed in upper cervical instabilities, it requires the guidance of fluoroscopic imaging. The fluoroscopy guidance is time-consuming and has the risks of accumulative radiation. Biplane fluoroscopy is also difficult in upper cervical pathologic conditions because of the use of cranial fixations. This study aimed to demonstrate that unicortical C1 lateral mass screws could be placed safely and rapidly without fluoroscopy guidance. METHODS: Between 2002 and 2008, 32 C1 lateral mass screws were inserted in 17 consecutive patients with various pathologic conditions involving either atlantoaxial or occipitocervical instability. RESULTS: C1 screw lengths ranged from 18 to 32 mm. The atlantoaxial fixation was performed in 13 patients, and C1 lateral mass screws were added to the occipitocervical construct in 3 patients, to the posterior cervical construct in 2 patients, and to the cervicothoracic construct in 1 patient. In 2 patients, because C1 lateral mass screws could not be inserted unilaterally, C1 pedicle screw analogs were inserted. There were no screw malpositions or neurovascular complications related to screw insertion. Operation time and intraoperative bleeding of the isolated atlantoaxial fixations were retrospectively evaluated. The mean follow-up was 32.3 months (range, 7-59 months). No screw loosening or construct failure was observed within this period. Postoperatively, 4 patients complained of hypoesthesia, whereas one patient had superficial wound infection. CONCLUSION: C1 lateral mass screws may be used safely and rapidly in upper cervical instabilities without intraoperative fluoroscopy guidance and the use of the spinal navigation systems. Preoperative planning and determining the ideal screw insertion point, the ideal trajections, and the lengths of the screws are the most important points.

Functional and clinical evaluation for the surgical treatment of degenerative stenosis of the lumbar spinal canal.

OBJECT: This study was designed to evaluate the efficacy of decompressive surgery for degenerative lumbar spinal stenosis (LSS) on a functional and clinical basis. METHODS: A prospective analysis and follow-up of 125 consecutive patients with degenerative LSS between 2000 and 2006 were performed. All patients underwent surgery for lumbar stenosis. Functional evaluations of the patients were performed using a treadmill, the visual analog scale, and the Oswestry Disability Questionnaire (ODQ). These parameters were recorded before surgery and the 3rd month and 1st and 2nd years after treatment. The first symptom time (FST), maximal walking duration (MWD), and thecal sac cross-sectional area (CSA) before and after surgery were also recorded. Statistical relations between variables were calculated. RESULTS: As patient ages increased, the CSA of the thecal sac decreased. Decompressive surgery reached the target according to the difference between the preoperative and postoperative thecal sac CSA. A correlation between the CSA of the thecal sac and FST, and between the CSA of the thecal sac and MWD could not be established. There was a significant correlation between the FST and MWD, and a negative correlation could be established between the MWD and the ODQ score. Surgery led to significant decreases in the ODQ score. Maximal improvement was observed in the 3rd month after decompressive surgery. CONCLUSIONS: The treatment for LSS should be decided using functional criteria; radiological criteria may not correlate with the severity of the disease. Improvements following lumbar decompression surgery continued within 1 year of treatment according to the ODQ and did not change significantly thereafter.

Circumferential total resection of cervical tumors: report of two consecutive cases and technical note.

To date, few studies have addressed the subaxial vertebrectomy technique and related anatomical landmarks in this method. Total spondylectomy is performed via piecemeal resection or en bloc removal in a one-stage procedure associated with stabilizing the spine and preserving neurological status. In this presentation, a circumferential total cervical tumor resection for subaxial cervical spine lesions was described. Two cases of subaxial cervical malignancy, one with primary C3 chondrosarcoma and the other with C4 lung adenosarcoma metastasis, were both treated by the anterior-posterior approach. The lesions could be removed macroscopically totally in both cases. The patients did well after surgery with preserved neurological status and they survived a considerable period without tumor recurrence. Subaxial total tumor resection can be performed safely while preserving vertebral arteries with adequate anatomical knowledge and careful surgical planning, and circumferential vertebrectomy (even intralesional) can provide a long recurrence-free survival period for patients suffering from subaxial spine tumors.

Effects of raloxifene on cerebral vasospasm after experimental Subarachnoid Hemorrhage in rabbits.

BACKGROUND: The aim of this study was to investigate the ability of a SERM, RLX, to prevent vasospasm in a rabbit model of SAH. METHODS: Thirty-four New Zealand white rabbits were allocated into 3 groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) sham operated (no SAH [n = 12]), (2) SAH only (n = 12), and (3) SAH plus RLX (n = 10). Basilar artery lumen areas and arterial wall thickness were measured to assess vasospams in all groups. RESULTS: There was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (P < .05). The difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements in the RLX-treated group was statistically significant (P < .05). The difference between the SAH group and the SAH + RLX group was also statistically significant (P < .05). CONCLUSIONS: These findings demonstrate that RLX has marked vasodilatatory effect in an experimental model of SAH in rabbits. This observation may have clinical implications suggesting that this SERM drug could be used as possible anti-vasospastic agent in patients without major adverse effects.

Delayed pseudomyelomeningocele: a rare complication after foramen magnum decompression for Chiari malformation.

BACKGROUND: A variety of complications after FMD with or without duraplasty for Chiari malformation have been described. Although cerebellar ptosis through the dural opening and pseudomeningocele are well-known rare complications of this procedure, spinal cord herniation manifesting as pseudomyelomeningocele formation has not previously been cited in the literature. In this report, we present a case of delayed pseudomyleomeningocele after FMD. CASE DESCRIPTION: A 22-year-old man presented with progressive spinal cord compression symptoms 7 years after undergoing FMD for Chiari malformation. Craniocervical MRI of the patient revealed pseudomyelomeningocele at C1 level together with cord distortion. The patient underwent untethering surgery for spinal cord adhesions; neural tissue was freed microsurgically from the adjacent structures and duraplasty was performed with synthetic graft. In the early postoperative period, his symptoms resolved moderately. CONCLUSION: Neural tissue shift including the spinal cord through the dural opening may occur after a large posterior fossa decompression without duraplasty for Chiari malformation. Postoperative inadequate CSF circulation due to arachnoid scarring around the decompression area may facilitate this type condition. Early diagnosis of such a complication is of vital importance to prevent serious neurologic deficits, and release surgery with proper duraplasty and also restoration of CSF circulation is the choice of treatment.

Sublabial transseptal approach to pituitary adenomas with special emphasis on rhinological complications.

OBJECTIVE: The aim of this presentation is to show that the sublabial transseptal transsphenoidal approach to pituitary adenomas is the least invasive anatomic route with the lowest postoperative complication rates. PATIENTS AND METHOD: This study was based on a retrospective analysis of 276 patients with a diagnosis of pituitary adenoma who were surgically treated via the sublabial transsphenoidal route. RESULTS: The overall complication rate of the presented series was 14.8%. The recurrence rate was 14.1%; there were no deaths or intranasal complications in this series. Postoperative rhinological complications, such as septal perforation, synechiae, and mucosal tear which impaired nasal function, occur rarely with this approach compared to other approaches. CONCLUSION: Besides the technical advantages of this approach, performance of the initial phase of the operation by an otorhinolaryngologic surgeon is the basis of the low intranasal complication rate in our series.

Posterior osseous bridging of C1.

The sulcus of the vertebral artery is located behind the lateral mass of the atlas and in some cases is converted into a foramen by anomalous ossification known as the posterior ponticulus (osseous bridge). This study involved anatomical observations of 158 isolated anatomical specimens of dry C1 vertebrae. The incidence and types of posterior osseous bridging were identified for the 158 dry samples of atlas vertebrae. In nine (5.6%) dry C1 vertebrae, partial osseous bridging was detected (bilaterally in eight vertebrae and unilaterally on the left in one). Complete osseous bridging (arcuate foramen) was observed in six (3.8%) dry C1 vertebrae (bilaterally in one vertebra, unilaterally on the left in three, and on the right in two). Awareness of the types of posterior osseous bridging of C1 in craniocervical junction surgery is essential, and may be helpful in surgical interventions in this region.

Metabolic changes during successful medical therapy for brain hydatid cyst: case report.

BACKGROUND: Medical therapy for hydatid disease of the brain has been reported with encouraging results especially in small or medium-sized cysts. To date, no other case correlating the metabolite levels of the cyst with albendazole treatment has been reported. CASE DESCRIPTION: A 52-year-old woman presented with left hemiparesis and seizure. Cranial magnetic resonance revealed a right frontal cystic mass lesion. A diagnosis of hydatid cyst was made, and she was put on medical therapy with albendazole. An MRS before the medical therapy was begun revealed the typical findings of a hydatid cyst with resonance of alanine, acetate, and succinate that were specific for hydatid disease, and additional nonspecific lactate peaks with an additional small peak of choline. Comparison between the multiple MRS examinations was made by comparing the metabolite ratios specific for hydatid disease to choline, which seemed stable from the beginning. Two sequential MRS imaging revealed a prominent decrease of the succinate and acetate resonance, accompanied by a smaller decline of the alanine resonance progressively, correlated with the conventional MRI findings of the cyst, which had a smaller size with blurred margins in the meantime. After 5 months of medical treatment, the cyst had completely disappeared. The patient has been monitored for 5 years and remains well without recurrence. CONCLUSIONS: This case provides additional proof that the brain hydatid cyst is a medically treatable disease in appropriate cases. Furthermore, the changes in the metabolic profile of the cyst, especially those regarding succinate and acetate may represent the efficacy of the medical treatment.

Medullomyoblastoma: teratoid nature of a quite rare neoplasm.

BACKGROUND: Medullomyoblastoma is a quite-rarely reported biphasic histologic variant of medulloblastoma since the first published description of a tumor consisting of medulloblastic and myogenic elements. Controversy over its origin still goes on. Here, an additional case of medullomyoblastoma variant is reported, and discussed are the clinicopathologic features and pathophysiologic mechanisms of and treatment options for this neoplasm. CASE REPORT: A 7-year-old girl was admitted to our clinic with headache, vomiting, and gait disturbances. An MRI scan on admission showed a solid tumor with a 2.5-cm axial diameter located in cerebellar vermis. The tumor was removed totally. Histologic examination revealed loose mesenchymal structures of the tumor and small muscle strands and isolated cells having large eosinophilic cytoplasm with striations. The muscular strands also demonstrated striations under light microscope. Glial fibrillary acidic protein, synaptophysin, and myogenin positivity are observed. CONCLUSION: There are some strong evidences that the medullomyoblastoma may be a teratoma. Survival time with the tumor is very short, outcome is poor, and the tumor can spread along cerebrospinal fluid pathways. Total resection, chemotherapy, and craniospinal irradiation are mainstays of the treatment of medullomyoblastomas.

Delayed neurotoxic complication of intracavitary bleomycin therapy for craniopharyngioma in a child who had previously undergone radiosurgery. Case report.

Local administration of bleomycin for the treatment of craniopharyngioma is occasionally associated with serious regional complications. The authors report a case of a delayed neurotoxic complication associated with bleomycin treatment in a patient who had previously undergone radiosurgery. A 14-year-old boy presented with a cyst recurrence of mixed-type craniopharyngioma. An Ommaya device was placed in the thin-walled cyst, and after confirmation that the device was watertight, the patient received a total dose of 75 mg bleomycin intratumorally during a 5-week period. Six weeks after the final drug administration, the patient experienced complex partial epileptic seizures; a few days later sudden right temporal hemianopia developed. Within 5 days the patient became totally blind in his right eye, and the condition did not respond to corticosteroid therapy. Although drug-related toxic complications occur commonly during the course of intracavitary bleomycin treatment, they may also be encountered during the follow-up period. The reason for this delayed complication could have been previous radiotherapy or hypersensitivity of the tumor capsule to the drug.