This study aimed to determine the justification for routine postoperative MRI (POMR) following su... more This study aimed to determine the justification for routine postoperative MRI (POMR) following surgical release of tethered cord (TC) given that an MR, in this situation, mostly serves as a baseline and rarely has immediate clinical implications. Furthermore, later in the course of the disease, the presence of retethering is mostly assessed by clinical parameters, rather than imaging. A single-center retrospective review of patients who underwent tethered cord release surgery between the years 1997 and 2009 at the Department of Pediatric Neurosurgery, Tel Aviv Medical Center, Israel was performed. Collected data including basis for diagnosis, pathology, associated clinical and radiologic findings, surgical procedure and outcome, postoperative follow-up and morbidities, and postoperative MRI findings were recorded and analyzed. One hundred forty patients operated upon between 1997 and 2009 for tethered cord syndrome were reviewed. Routine postoperative MR was performed in all cases 6-18 months after surgery. All cases were fully untethered. MR revealed relevant information in eight cases, two with residual dermoid, and six with significant terminal syrinx. None of these findings led to repeat surgery or special treatment. Retethering operations were performed in two cases in which retethering was diagnosed based on clinical evaluation. Based on analysis of our series of 140 consecutive patients who all underwent POMR 6-18 months after TC release, we suggest that POMR as routine clinical practice is not justified for uncomplicated cases of TC release. In cases of high risk for retethering, or significant preoperative syrinx or dermoid, POMR is recommended to establish a baseline for future clinical follow-up.
Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 pat... more Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 patients (NF1). They are found along the optic pathway and may involve the optic nerves, chiasm, retro-chiasmatic structures, and the optic radiations. NF1 associate OPG (NF1-OPG) have variable presentation, disease course and response to treatment. The optimal management is patient-specific and should be tailored by a multidisciplinary team. Age, sex, histology, and molecular markers may be important factors in the individualized decision-making process. Chemotherapy is the first-line treatment in cases of progressive tumors, and visual preservation is the main goal of treatment. Purpose In this paper we will review the disease, practical management, and recent advances of NF1-OPG.
Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 pat... more Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 patients (NF1). They are found along the optic pathway and may involve the optic nerves, chiasm, retro-chiasmatic structures, and the optic radiations. NF1 associate OPG (NF1-OPG) have variable presentation, disease course and response to treatment. The optimal management is patient-specific and should be tailored by a multidisciplinary team. Age, sex, histology, and molecular markers may be important factors in the individualized decision-making process. Chemotherapy is the first-line treatment in cases of progressive tumors, and visual preservation is the main goal of treatment. Purpose In this paper we will review the disease, practical management, and recent advances of NF1-OPG.
OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway glioma... more OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway gliomas (OPGs). Due to the rarity of this condition and the difficulty in differentiating IONGs from other types of OPGs in most clinical series, little is known about these tumors. Currently, due to lack of evidence, they are managed the same as any other OPG. METHODS The authors conducted a multicenter retrospective cohort study aimed at determining the natural history of IONGs. Included were patients with clear-cut glioma of the optic nerve without posterior (chiasmatic/hypothalamic) involvement. At least 1 year of follow-up, 2 MRI studies, and 2 neuro-ophthalmological examinations were required for inclusion. RESULTS Thirty-six patients with 39 tumors were included in this study. Age at diagnosis ranged between 6 months and 16 years (average 6 years). The mean follow-up time was 5.6 years. Twenty-five patients had neurofibromatosis Type 1. During the follow-up period, 59% of the tumors pro...
OBJECTIVE Hemorrhage (also known as apoplexy) in optic pathway gliomas (OPGs) is rare. Because of... more OBJECTIVE Hemorrhage (also known as apoplexy) in optic pathway gliomas (OPGs) is rare. Because of the variable presentations and low incidence of OPG hemorrhages, little is known about their clinical course and the best treatment options. The aim of this work was to review risk factors, clinical course, and treatment strategies of optic glioma hemorrhages in the largest possible number of cases. METHODS A total of 34 patients were analyzed. Nine new cases were collected, and 25 were identified in the literature. Data regarding demographics, radiological and histological features, treatment, and outcome were retrospectively reviewed. RESULTS The majority of patients were younger than 20 years. Only 3 patients were known to have neurofibromatosis. The histopathological diagnosis was pilocytic astrocytoma in the majority of cases. Five patients had intraorbital hemorrhages, whereas 29 patients had intracranial hemorrhage; the majority of intracranial bleeds were treated surgically. Six...
Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most mali... more Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant redu...
Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeuti... more Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeutic dilemma to the treating physicians. While chemotherapy is widely used for these tumors, our ability to predict radiological response is still lacking. In this study, we use volumetric imaging to examine in detail the long-term effect of chemotherapy on the tumor as well as its various sub-components. The tumors of 15 patients with OPG, treated with chemotherapy, were longitudinally measured using our novel, previously described volumetric method. Patients were treated with up to five lines of chemotherapy. Sufficient follow-up imaging data, and patient's numbers, allowed for analysis of two treatment lines. Volumetric measurements of the tumors were segmented into solid-non-enhancing, solid-enhancing, and cystic components. Outcome analysis was done per specific treatment line and for the overall follow-up period. An average reduction of 9.7% (±23%) in the gross-total-solid volume ...
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, Jan 4, 2014
Infantile hemangiomas are the most common benign tumors in children. However, cranial involvement... more Infantile hemangiomas are the most common benign tumors in children. However, cranial involvement of such lesions is rare. Current treatment options for hemangiomas in various locations that would be endangering or disfiguring include follow-up, surgical removal, or administration of corticosteroids, interferon-α, thalidomide, vincristine, propranolol, and laser therapy. We describe an infant who presented with an extensive cranial hemangioma (proven by a biopsy). The child was treated with propranolol. Clinical and radiological follow-up for over a year showed significant reduction in tumor size without adverse clinical symptoms. Propranolol is a valid treatment for large cranial hemangiomas, avoiding the risks involved in surgeries.
Optic pathway gliomas (OPG) are the most common primary tumors of the visual pathways, and consti... more Optic pathway gliomas (OPG) are the most common primary tumors of the visual pathways, and constitute 1% of all brain tumors and 5% of all brain tumors in children. Among Neurofibromatosis type 1 patients (a hereditary genetic disorder which is characterized by higher incidence of tumors from a neurocutaneous origin) it is the most frequent tumor and it constitutes between 15 to 20 percent of all nervous system tumors. These tumors are stable most of the time and remain indolent for many years after diagnosis, especially in patients suffering from Neurofibromatosis type 1. However, amongst some of the patients suffering from OPG, these tumors develop progressive characteristics and can cause visual disturbances, endocrine dysfunction, blindness and even death. Patients with aggressive tumors will need treatment, which can be either surgery, chemotherapy or radiation therapy. Today, the treating physicians face substantial difficulty in estimating the course the tumor will take, choo...
Advances and Technical Standards in Neurosurgery, 2014
Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-o... more Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-oncology. Recent technological advances in imaging, surgery, and chemotherapy may lead to better understanding of the pathophysiology and better clinical results. This chapter reviews these advances and the current treatment paradigms.
International Journal of Computer Assisted Radiology and Surgery, 2013
Volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as t... more Volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as they require the delineation of the PN boundaries, which is mostly impractical in the daily clinical setup. Accurate volumetric measurements are seldom performed for these tumors mainly due to their great dispersion, size and multiple locations. This paper presents a semiautomatic method for segmentation of PN from STIR MRI scans. Plexiform neurofibroma interactive segmentation tool (PNist) is a new tool to segment PNs in STIR MRI scans. The method is based on histogram tumor models computed from a training set. Experimental results from 28 datasets show an average absolute volume difference of 6.8 % with an average user time of approximately 7 min versus more than 13 min with manual delineation. In complex cases, the PNist user time is less than half in compared to state-of-the-art tools. PNist is a new method for the semiautomatic segmentation of PN lesions. Its simplicity and reliability make it unique among other state-of-the-art methods. It has the potential to become a clinical tool that allows the reliable evaluation of PN burden and progression.
This study aimed to determine the justification for routine postoperative MRI (POMR) following su... more This study aimed to determine the justification for routine postoperative MRI (POMR) following surgical release of tethered cord (TC) given that an MR, in this situation, mostly serves as a baseline and rarely has immediate clinical implications. Furthermore, later in the course of the disease, the presence of retethering is mostly assessed by clinical parameters, rather than imaging. A single-center retrospective review of patients who underwent tethered cord release surgery between the years 1997 and 2009 at the Department of Pediatric Neurosurgery, Tel Aviv Medical Center, Israel was performed. Collected data including basis for diagnosis, pathology, associated clinical and radiologic findings, surgical procedure and outcome, postoperative follow-up and morbidities, and postoperative MRI findings were recorded and analyzed. One hundred forty patients operated upon between 1997 and 2009 for tethered cord syndrome were reviewed. Routine postoperative MR was performed in all cases 6-18 months after surgery. All cases were fully untethered. MR revealed relevant information in eight cases, two with residual dermoid, and six with significant terminal syrinx. None of these findings led to repeat surgery or special treatment. Retethering operations were performed in two cases in which retethering was diagnosed based on clinical evaluation. Based on analysis of our series of 140 consecutive patients who all underwent POMR 6-18 months after TC release, we suggest that POMR as routine clinical practice is not justified for uncomplicated cases of TC release. In cases of high risk for retethering, or significant preoperative syrinx or dermoid, POMR is recommended to establish a baseline for future clinical follow-up.
Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 pat... more Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 patients (NF1). They are found along the optic pathway and may involve the optic nerves, chiasm, retro-chiasmatic structures, and the optic radiations. NF1 associate OPG (NF1-OPG) have variable presentation, disease course and response to treatment. The optimal management is patient-specific and should be tailored by a multidisciplinary team. Age, sex, histology, and molecular markers may be important factors in the individualized decision-making process. Chemotherapy is the first-line treatment in cases of progressive tumors, and visual preservation is the main goal of treatment. Purpose In this paper we will review the disease, practical management, and recent advances of NF1-OPG.
Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 pat... more Background Optic Pathway Gliomas (OPG) are the most common brain tumor in Neurofibromatosis 1 patients (NF1). They are found along the optic pathway and may involve the optic nerves, chiasm, retro-chiasmatic structures, and the optic radiations. NF1 associate OPG (NF1-OPG) have variable presentation, disease course and response to treatment. The optimal management is patient-specific and should be tailored by a multidisciplinary team. Age, sex, histology, and molecular markers may be important factors in the individualized decision-making process. Chemotherapy is the first-line treatment in cases of progressive tumors, and visual preservation is the main goal of treatment. Purpose In this paper we will review the disease, practical management, and recent advances of NF1-OPG.
OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway glioma... more OBJECTIVE Isolated optic nerve gliomas (IONGs) constitute a rare subgroup of optic pathway gliomas (OPGs). Due to the rarity of this condition and the difficulty in differentiating IONGs from other types of OPGs in most clinical series, little is known about these tumors. Currently, due to lack of evidence, they are managed the same as any other OPG. METHODS The authors conducted a multicenter retrospective cohort study aimed at determining the natural history of IONGs. Included were patients with clear-cut glioma of the optic nerve without posterior (chiasmatic/hypothalamic) involvement. At least 1 year of follow-up, 2 MRI studies, and 2 neuro-ophthalmological examinations were required for inclusion. RESULTS Thirty-six patients with 39 tumors were included in this study. Age at diagnosis ranged between 6 months and 16 years (average 6 years). The mean follow-up time was 5.6 years. Twenty-five patients had neurofibromatosis Type 1. During the follow-up period, 59% of the tumors pro...
OBJECTIVE Hemorrhage (also known as apoplexy) in optic pathway gliomas (OPGs) is rare. Because of... more OBJECTIVE Hemorrhage (also known as apoplexy) in optic pathway gliomas (OPGs) is rare. Because of the variable presentations and low incidence of OPG hemorrhages, little is known about their clinical course and the best treatment options. The aim of this work was to review risk factors, clinical course, and treatment strategies of optic glioma hemorrhages in the largest possible number of cases. METHODS A total of 34 patients were analyzed. Nine new cases were collected, and 25 were identified in the literature. Data regarding demographics, radiological and histological features, treatment, and outcome were retrospectively reviewed. RESULTS The majority of patients were younger than 20 years. Only 3 patients were known to have neurofibromatosis. The histopathological diagnosis was pilocytic astrocytoma in the majority of cases. Five patients had intraorbital hemorrhages, whereas 29 patients had intracranial hemorrhage; the majority of intracranial bleeds were treated surgically. Six...
Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most mali... more Temozolomide (TMZ) is an alkylating agent that has become the mainstay treatment of the most malignant brain cancer, glioblastoma multiforme (GBM). Unfortunately only a limited number of patients positively respond to it. It has been shown that zinc metal reestablishes chemosensitivity but this effect has not been tested with TMZ. Using both in vitro and in vivo experimental approaches, we investigated whether addition of zinc to TMZ enhances its cytotoxicity against GBM. In vitro cell viability analysis showed that the cytotoxic activity of TMZ was substantially increased with addition of zinc and this response was accompanied by an elevation of p21, PUMA, BAX and Caspase-3 expression and a decrease in growth fraction as manifested by low ki67 and lower colony formation. Analysis of GBM as intracranial xenografts in athymic mice and administration of concurrent TMZ and zinc yielded results consistent with those of the in vitro analyses. The co-treatment resulted in significant redu...
Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeuti... more Optic pathway gliomas (OPG) represent 5% of pediatric brain tumors and compose a major therapeutic dilemma to the treating physicians. While chemotherapy is widely used for these tumors, our ability to predict radiological response is still lacking. In this study, we use volumetric imaging to examine in detail the long-term effect of chemotherapy on the tumor as well as its various sub-components. The tumors of 15 patients with OPG, treated with chemotherapy, were longitudinally measured using our novel, previously described volumetric method. Patients were treated with up to five lines of chemotherapy. Sufficient follow-up imaging data, and patient's numbers, allowed for analysis of two treatment lines. Volumetric measurements of the tumors were segmented into solid-non-enhancing, solid-enhancing, and cystic components. Outcome analysis was done per specific treatment line and for the overall follow-up period. An average reduction of 9.7% (±23%) in the gross-total-solid volume ...
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery, Jan 4, 2014
Infantile hemangiomas are the most common benign tumors in children. However, cranial involvement... more Infantile hemangiomas are the most common benign tumors in children. However, cranial involvement of such lesions is rare. Current treatment options for hemangiomas in various locations that would be endangering or disfiguring include follow-up, surgical removal, or administration of corticosteroids, interferon-α, thalidomide, vincristine, propranolol, and laser therapy. We describe an infant who presented with an extensive cranial hemangioma (proven by a biopsy). The child was treated with propranolol. Clinical and radiological follow-up for over a year showed significant reduction in tumor size without adverse clinical symptoms. Propranolol is a valid treatment for large cranial hemangiomas, avoiding the risks involved in surgeries.
Optic pathway gliomas (OPG) are the most common primary tumors of the visual pathways, and consti... more Optic pathway gliomas (OPG) are the most common primary tumors of the visual pathways, and constitute 1% of all brain tumors and 5% of all brain tumors in children. Among Neurofibromatosis type 1 patients (a hereditary genetic disorder which is characterized by higher incidence of tumors from a neurocutaneous origin) it is the most frequent tumor and it constitutes between 15 to 20 percent of all nervous system tumors. These tumors are stable most of the time and remain indolent for many years after diagnosis, especially in patients suffering from Neurofibromatosis type 1. However, amongst some of the patients suffering from OPG, these tumors develop progressive characteristics and can cause visual disturbances, endocrine dysfunction, blindness and even death. Patients with aggressive tumors will need treatment, which can be either surgery, chemotherapy or radiation therapy. Today, the treating physicians face substantial difficulty in estimating the course the tumor will take, choo...
Advances and Technical Standards in Neurosurgery, 2014
Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-o... more Optic pathway gliomas (OPGs) are among the most challenging neoplasms in modern pediatric neuro-oncology. Recent technological advances in imaging, surgery, and chemotherapy may lead to better understanding of the pathophysiology and better clinical results. This chapter reviews these advances and the current treatment paradigms.
International Journal of Computer Assisted Radiology and Surgery, 2013
Volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as t... more Volumetric measurements of plexiform neurofibromas (PNs) are time consuming and error prone, as they require the delineation of the PN boundaries, which is mostly impractical in the daily clinical setup. Accurate volumetric measurements are seldom performed for these tumors mainly due to their great dispersion, size and multiple locations. This paper presents a semiautomatic method for segmentation of PN from STIR MRI scans. Plexiform neurofibroma interactive segmentation tool (PNist) is a new tool to segment PNs in STIR MRI scans. The method is based on histogram tumor models computed from a training set. Experimental results from 28 datasets show an average absolute volume difference of 6.8 % with an average user time of approximately 7 min versus more than 13 min with manual delineation. In complex cases, the PNist user time is less than half in compared to state-of-the-art tools. PNist is a new method for the semiautomatic segmentation of PN lesions. Its simplicity and reliability make it unique among other state-of-the-art methods. It has the potential to become a clinical tool that allows the reliable evaluation of PN burden and progression.
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Papers by Shlomi Constantini