Carlo Gulì

Role of Inflammation and Oxidative Stress Mediators in Gliomas

Gliomas are the most common primary brain tumors of the central nervous system. Despite relevant progress in conventional treatments, the prognosis of such tumors remains almost invariably dismal. The genesis of gliomas is a complex, multistep process that includes cellular neoplastic transformation, resistance to apoptosis, loss of control of the cell cycle, angiogenesis, and the acquisition of invasive properties. Among a number of different biomolecular events, the existence of molecular connections between inflammation and oxidative stress pathways and the development of this cancer has been demonstrated. In particular, the tumor microenvironment, which is largely orchestrated by inflammatory molecules, is an indispensable participant in the neoplastic process, promoting proliferation, survival and migration of such tumors. Proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma, as well as chemokines and prostaglandins, are synthesized by resident brain cells and lymphocytes invading the affected brain tissue. Key mediators of cancer progression include nuclear factor-kappaB, reactive oxygen and nitrogen species, and specific microRNAs. The collective activity of these mediators is largely responsible for a pro-tumorigenic response through changes in cell proliferation, cell death, cellular senescence, DNA mutation rates, DNA methylation and angiogenesis. We provide a general overview of the connection between specific inflammation and oxidative stress pathway molecules and gliomas. The elucidation of specific effects and interactions of these factors may provide the opportunity for the identification of new target molecules leading to improved diagnosis and treatment.

With a Little Help from My Friends: The Role of Intraoperative Fluorescent Dyes in the Surgical Management of High-Grade Gliomas

High-grade gliomas (HGGs) are the most frequent primary malignant brain tumors in adults, which lead to death within two years of diagnosis. Maximal safe resection of malignant gliomas as the first step of multimodal therapy is an accepted goal in malignant glioma surgery. Gross total resection has an important role in improving overall survival (OS) and progression-free survival (PFS), but identification of tumor borders is particularly difficult in HGGS. For this reason, imaging adjuncts, such as 5-aminolevulinic acid (5-ALA) or fluorescein sodium (FS) have been proposed as superior strategies for better defining the limits of surgical resection for HGG. 5-aminolevulinic acid (5-ALA) is implicated as precursor in the synthetic pathway of heme group. Protoporphyrin IX (PpIX) is an intermediate compound of heme metabolism, which produces fluorescence when excited by appropriate light wavelength. Malignant glioma cells have the capacity to selectively synthesize or accumulate 5-ALA-derived porphyrins after exogenous administration of 5-ALA. Fluorescein sodium (FS), on the other hand, is a fluorescent substance that is not specific to tumor cells but actually it is a marker for compromised blood-brain barrier (BBB) areas. Its effectiveness is confirmed by multicenter phase-II trial (FLUOGLIO) but lack of randomized phase III trial data. We conducted an analytic review of the literature with the objective of identifying the usefulness of 5-ALA and FS in HGG surgery in adult patients.

Reconstruction of Vertebral Body After Radiofrequency Ablation and Augmentation in Dorsolumbar Metastatic Vertebral Fracture: Analysis of Clinical and Radiological Outcome in a Clinical Series of 18 Patients

BACKGROUND Painful spinal metastases usually occur in malignant neoplastic disease. Treatment for bone metastases has been largely conservative, and it includes the use of high doses of analgesics, radiotherapy, chemotherapy, hormone therapy, and bisphosphonates; however, results are sometimes transient and ineffective. In the presence of neurological involvement a surgical strategy should be considered. Recently, percutaneous procedures such as radiofrequency ablation, vertebroplasty, and kyphoplasty have been introduced as palliative techniques to treat painful vertebral metastases [3, 11, 25]. METHODS In our study we combined the use of radiofrequency ablation with vertebroplasty in the treatment of dorsolumbar metastatic vertebral fractures in order to examine the relationship between restoration of the vertebral structure and decrease in pain. From January 2014 to March 2015 we retrospectively analyzed 18 patients with malignant vertebral lesions who underwent radiofrequency ablation with vertebroplasty followed by cementoplasty, with posterior transpedicle fixation on levels near the lesions. The parameters examined were: demographics, pain relief, and the distribution of polymethylmethacrylate (PMMA) determined by the mean Saliou filling score; all complications were recorded. FINDINGS The mean age of the patients was 55.72 years (range 34-69); average operative time was 60.4 min (range, 51-72). The average pain index score (visual analog score; VAS) decreased significantly from 8.05 at baseline to 3.0 (p < 0.05) after 6 months. The Saliou filling score revealed a distribution of PMMA in the vertebral body that was satisfactory (12-18) in eight patients, mediocre (6-12) in seven patients, and inadequate (0-6) in the remaining three patients. In two vertebrae, minimal asymptomatic cement leakage occurred in the lateral recess without neurological damage. No pulmonary embolism and no visceral or neural damage was recorded. CONCLUSION Radiofrequency ablation combined with vertebroplasty seems to achieve rapid and lasting improvement in clinical symptoms in patients with malignant vertebral lesions. There was wide diffusion of PMMA in the vertebral body, with a mean cement volume of 4.5 ml.

End-of-Life Care in High-Grade Glioma Patients. The Palliative and Supportive Perspective

High-grade gliomas (HGGs) are the most frequently diagnosed primary brain tumors. Even though it has been demonstrated that combined surgical therapy, chemotherapy, and radiotherapy improve survival, HGGs still harbor a very poor prognosis and limited overall survival. Differently from other types of primary neoplasm, HGG manifests also as a neurological disease. According to this, palliative care of HGG patients represents a peculiar challenge for healthcare providers and caregivers since it has to be directed to both general and neurological cancer symptoms. In this way, the end-of-life (EOL) phase of HGG patients appears to be like a journey through medical issues, progressive neurological deterioration, and psychological, social, and affective concerns. EOL is intended as the time prior to death when symptoms increase and antitumoral therapy is no longer effective. In this phase, palliative care is intended as an integrated support aimed to reduce the symptoms burden and improve the Quality Of Life (QOL). Palliative care is represented by medical, physical, psychological, spiritual, and social interventions which are primarily aimed to sustain patients’ functions during the disease time, while maintaining an acceptable quality of life and ensuring a dignified death. Since HGGs represent also a family concern, due to the profound emotional and relational issues that the progression of the disease poses, palliative care may also relieve the distress of the caregivers and increase the satisfaction of patients’ relatives. We present the results of a literature review addressed to enlighten and classify the best medical, psychological, rehabilitative, and social interventions that are addressed both to patients and to their caregivers, which are currently adopted as palliative care during the EOL phase of HGG patients in order to orientate the best medical practice in HGG management.

Surgical nuances on the treatment of giant dumbbell cervical spine schwannomas: description of a challenging case and review of the literature

We report a case of a giant intra and extradural cervical schwannoma in a patient affected by a severe myelo-radiculopathy. Clinical features, diagnosis and the issues concerning the surgical management of this benign tumor are discussed. We also review similar cases previously reported in the literature. A 50-year old caucasian woman was complaining of a 1 year of neck pain and worsening motor impairment in all four limbs causing the inability to walk. Neuroradiological assessment revealed a suspected schwannoma involving the nerve roots from C3 to C5, compressing and deviating the spinal cord. The vertebral artery was also encased within the lesion, but still patent. A posterior cervical laminectomy with a microsurgical extradural resection of the lesion was performed. Moreover, an accurate dissection of the lesion from the vertebral artery and the resection of the intraspinal component was achieved. Vertebral fixation with screws on the lateral masses of C3, C5 and C6 and a hook on C1 was performed. The procedure was secured using electroneurophysiological monitoring. A progressive improvement of the motor functions was achieved. A cervical post-contrast MRI revealed optimal medullary decompression and a gross-total resection of the lesion. Schwannomas are benign, slowly growing lesions which may cause serious neurological deficit. Early diagnosis is necessary and it maybe aided by imaging studies such as MRI or CT. The accepted treatment for these tumors is surgical resection and, when indicated, vertebral fixation.

Percutaneous Pedicle-Lengthening Osteotomy in Minimal Invasive Spinal Surgery to Treat Degenerative Lumbar Spinal Stenosis: A Single-Center Preliminary Experience

Abstract Background Lumbar spinal stenosis (LSS) is a narrowing of the spinal canal due to spinal degeneration, and its main clinical symptom is neurogenic claudication. Surgical treatment is pursued for patients who do not improve with conservative care. Patients with symptomatic LSS who also have significant medical comorbidities, although clearly in need of intervention, are unattractive candidates for traditional open lumbar decompressive procedures. Thus it is important to explore minimally invasive surgical techniques to treat select patients with LSS. Methods This retrospective case series evaluated the clinical and radiographic outcomes of a new minimally invasive procedure to treat LSS: pedicle‐lengthening osteotomy using the ALTUM system ((Innovative Surgical Designs, Inc., Bloomington, Indiana, United States). Peri‐ and postoperative demographic and radiographic data were collected from a clinical series of seven patients with moderate LSS who were > 60 years of age. Clinical outcome was evaluated using visual analog scale (VAS) scores and the spinal canal area on computed tomography scans. Results Twelve months after the procedure, scoring revealed a median improvement of 3.7 on the VAS for the back and 6.3 on the VAS for the leg, compared with the preoperative baseline (p < 0.05). The postoperative central area of the lumbar canal was significantly increased, by 0.39 cm2; the right and left neural foramina were enlarged by 0.29 cm2 and 0.47 cm2, respectively (p < 0.05). Conclusions In this preliminary study, the ALTUM system showed a good clinical and radiologic outcome 1 year after surgery. In an older or high‐risk population, a short minimally invasive procedure may be beneficial for treating LSS.

A thoracic vertebral localization of a metastasized cutaneous Merkel cell carcinoma: Case report and review of literature

Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor, which may be related to sun exposure. It can metastasize to lungs, liver and bone, leading to severe morbidity and mortality. Vertebral metastases from MCC are rare. The authors report the tenth case in the literature, a 59-year-old patient with MCC, which was primarily localized in the scalp, and later provoked distant metastasis to the thoracic spinal column. Case Description: A 59-year-old woman was admitted at our Unit of Neurosurgery with a 4-month history of progressive and severe dorsal back pain, without neurological signs. The patient had been surgically treated for a recidivated MCC in the occipital region in 2007, 2011, and 2013. (In 2013, the surgical treatment also included lateral cervical lymph node dissection). Chemotherapy and radiotherapy had come after the treatments. Magnetic resonance imaging (MRI) of the dorsal spine showed metastatic vertebral involvement with cord impingement of the T7-T8 levels. A total body CT scan revealed lungs and liver metastases, besides vertebral district. After a multidisciplinary consult a palliative surgery was decided and a posterior dorsal approach was employed: Radiofrequency (RF) thermoablation was followed by the injection of cement of T7 and T8 and transpedicle fixation T5-T9. The postoperative course was uneventful and followed by a further adjuvant therapy Conclusion: Spinal metastases from MCC are described in literature only exceptionally. The clinical course is presented, along with a review of literature.

Never say never again: A bone graft infection due to a hornet sting, thirty-nine years after cranioplasty

Background: Cranioplasty (CP) is a widespread surgical procedure aimed to restore skull integrity and physiological cerebral hemodynamics, to improve neurological functions and to protect the underlying brain after a life-saving decompressive craniectomy (DC). Nevertheless, CP is still burdened by surgical complications, among which early or late graft infections are the most common outcome-threatening ones. Case Description: We report the case of 48-year-old man admitted to our neurosurgical unit because of a painful right frontal swelling and 1-week purulent discharge from a cutaneous fistula. He had been undergone frontal CP because of severe traumatic brain injury (TBI) when he was 9-year-old. Since then, his medical history has been being unremarkable without any surgical or infective complication of the graft for 39 years, until he was accidentally stung by a hornet in the frontal region. After the CT scan and laboratory findings had evidenced a probable infection of the graft, the patient was treated by vancomycin and cefepime before he underwent surgical revision of its former CP, with the removal of the graft and the debridement of the surgical field. Subsequent bacteriological tests revealed Staphylococcus aureus as causal agent of that infection. Conclusion: This case illustrates an anecdotal example of very late CP infection, due to an unpredictable accident. Due to lack of consensus on risk factors and on conservative or surgical strategy in case of graft infection, we aimed to share our surgical experience.

EMG-Guided Percutaneous Placement of Cement-Augmented Pedicle Screws for Osteoporotic Thoracolumbar Burst Fractures

BACKGROUND Percutaneous techniques have increasingly gained popularity in recent years. The application of technological innovation, including neuromonitoring techniques, has the potential to increase the safety and efficacy of these procedures. METHODS Thirty patients suffering from osteoporotic dorsolumbar burst fracture were prospectively enrolled in this study. The patients underwent percutaneous fenestrated pedicle screw fixation augmented with polymethylmethacrylate (PMMA) injection. A novel surgeon-dedicated neuromonitoring device was used in order to increase the safety and the accuracy of the screw insertion. A second group of 30 patients who did not undergo neuromonitoring during percutaneous pedicle screw placement, matched for demographic characteristics, constituted the control group. FINDINGS A total of 296 screws were inserted. All treated patients had a good outcome, documented by an improvement in visual analogue scale (VAS) scores. Excellent trajectories were achieved in all patients. Cobbs angle and anterior vertebral height were satisfactorily restored in all study group patients. Three misplaced screws in three patients and a case of PMMA leakage without neurological deficits were observed in the control group, whereas no complication was recorded in the study group (p = 0.03). CONCLUSIONS Neuromonitoring in cement-augmented percutaneous pedicle screw placement appears to improve surgeon confidence during surgery, reducing the risk of screw misplacement or cement leakage.

Spinal Cord Stimulation: An Alternative Concept of Rehabilitation?

BACKGROUND Chronic low back and leg pain is a disabling condition, affecting, in most cases, older patients with congenital or acquired spinal stenosis or patients with failed back surgery syndrome. Spinal cord stimulation has been introduced as an effective therapeutic option for those patients who have previously been operated without significant clinical benefits, or for all those patients who are ineligible for traditional surgery. METHODS We report our experience with ten patients treated with spinal cord stimulation plus medication and physical therapy between November 2014 and September 2015. Inclusion criteria were: previous surgical treatments for lumbar stenosis and metameric instability and persistent or ingravescent disabling low back and leg pain, with a mean duration of symptoms of at least 18 months. A visual analog scale (VAS) was employed for back and leg pain, and the Oswestry Disability Index (ODI) score was determined, and findings were analyzed after 6 months. FINDINGS No intra- or postoperative complication was recorded. The mean VAS score for back pain decreased from 7.5 to 2.9, while leg VAS decreased from 8.2 to 3.0. Analysis of ODI values showed evident improvement in daily life activities, ranging from a median value of 75.7% to 32.7 % after the stimulation. CONCLUSION Spinal cord stimulation has a recognized impact on the pain and on the quality of life of patients with failed back surgery syndrome.