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Jonathan P. S. Knisely, Rohan Ramakrishna and Theodore H. Schwartz

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Danielle Golub, Jonathan Hyde, Siddhant Dogra, Joseph Nicholson, Katherine A. Kirkwood, Paulomi Gohel, Stephen Loftus and Theodore H. Schwartz

OBJECTIVE

High-grade gliomas (HGGs) continue to carry poor prognoses, and patient outcomes depend heavily on the extent of resection (EOR). The utility of conventional image-guided surgery is limited by intraoperative brain shift. More recent techniques to maximize EOR, including intraoperative imaging and the use of fluorescent dyes, combat these limitations. However, the relative efficacy of these two techniques has never been systematically compared. Thus, the authors performed an exhaustive systematic review in conjunction with quantitative network meta-analyses to evaluate the comparative effectiveness of 5-aminolevulinic acid (5-ALA) and intraoperative MRI (IMRI) in optimizing EOR in HGG. They secondarily analyzed associated progression-free and overall survival and performed subgroup analyses by level of evidence.

METHODS

PubMed, Embase, Cochrane Central, and Web of Science were searched for studies evaluating conventional neuronavigation, IMRI, and 5-ALA in HGG resection. The primary study endpoint was the proportion of patients attaining gross-total resection (GTR), defined as 100% elimination of contrast-enhancing lesion on postoperative MRI. Secondary endpoints included overall and progression-free survival and subgroup analyses for level of evidence. Comparative efficacy analysis of IMRI and 5-ALA was performed using Bayesian network meta-analysis models.

RESULTS

This analysis included 11 studies. In a classic meta-analysis, both IMRI (OR 4.99, 95% CI 2.65–9.39, p < 0.001) and 5-ALA (OR 2.866, 95% CI 2.127–3.863, p < 0.001) were superior to conventional navigation in achieving GTR. Bayesian network analysis was employed to indirectly compare IMRI to 5-ALA, and no significant difference in GTR was found between the two (OR 1.9 favoring IMRI, 95% CI 0.905–3.989, p = 0.090). A handful of studies additionally suggested that the use of either IMRI (2 and 4 studies, respectively) or 5-ALA (2 and 2 studies, respectively) improves progression-free and overall survival.

CONCLUSIONS

IMRI and 5-ALA are individually superior to conventional neuronavigation for achieving GTR of HGG. Between IMRI and 5-ALA, neither method is clearly more effective. Future studies evaluating the comparative cost and surgical time associated with IMRI and 5-ALA will better inform any cost-benefit analysis.

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Malte Ottenhausen, Kavelin Rumalla, Andrew F. Alalade, Prakash Nair, Emanuele La Corte, Iyan Younus, Jonathan A. Forbes, Atef Ben Nsir, Matei A. Banu, Apostolos John Tsiouris and Theodore H. Schwartz

OBJECTIVE

Anterior skull base meningiomas are benign lesions that cause neurological symptoms through mass effect on adjacent neurovascular structures. While traditional transcranial approaches have proven to be effective at removing these tumors, minimally invasive approaches that involve using an endoscope offer the possibility of reducing brain and nerve retraction, minimizing incision size, and speeding patient recovery; however, appropriate case selection and results in large series are lacking.

METHODS

The authors developed an algorithm for selecting a supraorbital keyhole minicraniotomy (SKM) for olfactory groove meningiomas or an expanded endoscopic endonasal approach (EEA) for tuberculum sella (TS) or planum sphenoidale (PS) meningiomas based on the presence or absence of olfaction and the anatomical extent of the tumor. Where neither approach is appropriate, a standard transcranial approach is utilized. The authors describe rates of gross-total resection (GTR), olfactory outcomes, and visual outcomes, as well as complications, for 7 subgroups of patients. Exceptions to the algorithm are also discussed.

RESULTS

The series of 57 patients harbored 57 anterior skull base meningiomas; the mean tumor volume was 14.7 ± 15.4 cm3 (range 2.2–66.1 cm3), and the mean follow-up duration was 42.2 ± 37.1 months (range 2–144 months). Of 19 patients with olfactory groove meningiomas, 10 had preserved olfaction and underwent SKM, and preservation of olfaction in was seen in 60%. Of 9 patients who presented without olfaction, 8 had cribriform plate invasion and underwent combined SKM and EEA (n = 3), bifrontal craniotomy (n = 3), or EEA (n = 2), and one patient without both olfaction and cribriform plate invasion underwent SKM. GTR was achieved in 94.7%. Of 38 TS/PS meningiomas, 36 of the lesions were treated according to the algorithm. Of these 36 meningiomas, 30 were treated by EEA and 6 by craniotomy. GTR was achieved in 97.2%, with no visual deterioration and one CSF leak that resolved by placement of a lumbar drain. Two patients with tumors that, based on the algorithm, were not amenable to an EEA underwent EEA nonetheless: one had GTR and the other had a residual tumor that was followed and removed via craniotomy 9 years later.

CONCLUSIONS

Utilizing a simple algorithm aimed at preserving olfaction and vision and based on maximizing use of minimally invasive approaches and selective use of transcranial approaches, the authors found that excellent outcomes can be achieved for anterior skull base meningiomas.

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Nachshon Knoller, Gustavo Auerbach, Valentin Fulga, Gabriel Zelig, Josef Attias, Ronit Bakimer, Jonathan B. Marder, Eti Yoles, Michael Belkin, Michal Schwartz and Moshe Hadani

Object. A Phase I, open-label nonrandomized study was conducted to assess the safety and tolerability of incubated autologous macrophages administered to patients with acute complete spinal cord injury (SCI).

Methods. This therapy was first tested in rat models of spinal cord transection and contusion, in which it was shown to promote motor recovery. The procedure developed for clinical use consists of isolating monocytes from patient blood and incubating them ex vivo with autologous dermis. The resulting incubated autologous macrophages were injected into the patient's spinal cord immediately caudal to the lesion within 14 days of injury. Patients underwent preoperative and follow-up neurological assessment (American Spinal Injury Association [ASIA] standards), electrophysiological monitoring (motor evoked and/or somatosensory evoked potentials), magnetic resonance imaging, and safety monitoring. Before macrophage administration, complete neurological functional loss (ASIA Grade A) was confirmed in all patients. Of the eight patients in the study, three recovered clinically significant neurological motor and sensory function (ASIA Grade C status). During the study period, some adverse events were encountered, the most serious of which involved two cases of pulmonary embolism and one case of osteomyelitis that were treated and resolved without further complication. These and other adverse events appear to be similar to those encountered in other spinal cord—injured patients and are not considered a consequence of the experimental therapy.

Conclusions. It is concluded that incubated autologous macrophage cell therapy is well tolerated in patients with acute SCI. Further clinical evaluation is warranted.

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Jonathan A. Forbes, Edgar G. Ordóñez-Rubiano, Hilarie C. Tomasiewicz, Matei A. Banu, Iyan Younus, Georgiana A. Dobri, C. Douglas Phillips, Ashutosh Kacker, Babacar Cisse, Vijay K. Anand and Theodore H. Schwartz

OBJECTIVE

Intrinsic third ventricular craniopharyngiomas (IVCs) have been reported by some authors to “pose the greatest surgical challenge” of all craniopharyngiomas (CPAs). A variety of open microsurgical approaches have historically been used for resection of these tumors. Despite increased utilization of the endoscopic endonasal approach (EEA) for resection of CPAs in recent years, many authors continue to recommend against use of the EEA for resection of IVCs. In this paper, the authors present the largest series to date utilizing the EEA to remove IVCs.

METHODS

The authors reviewed a prospectively acquired database of the EEA for resection of IVCs over 14 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital. Preoperative MR images were examined independently by two neurosurgeons and a neuroradiologist to identify IVCs. Pre- and postoperative endocrinological, ophthalmological, radiographic, and other morbidities were determined from retrospective chart review and volumetric radiographic analysis.

RESULTS

Between January 2006 and August 2017, 10 patients (4 men, 6 women) ranging in age from 26 to 67 years old, underwent resection of an IVC utilizing the EEA. Preoperative endocrinopathy was present in 70% and visual deterioration in 60%. Gross-total resection (GTR) was achieved in 9 (90%) of 10 patients, with achievement of near-total (98%) resection in the remaining patient. Pathology was papillary in 30%. Closure incorporated a “gasket-seal” technique with nasoseptal flap coverage and either lumbar drainage (9 patients) or a ventricular drain (1 patient). Postoperatively, complete anterior and posterior pituitary insufficiency was present in 90% and 70% of patients, respectively. In 4 patients with normal vision prior to surgery, 3 had stable vision following tumor resection. One patient noted a new, incongruous, left inferior homonymous quadrantanopsia postoperatively. In the 6 patients who presented with compromised vision, 2 reported stable vision following surgery. Each of the remaining 4 patients noted significant improvement in vision after tumor resection, with complete restoration of normal vision in 1 patient. Aside from the single case (10%) of visual deterioration referenced above, there were no instances of postoperative neurological decline. Postoperative CSF leakage occurred in 1 morbidly obese patient who required reoperation for revision of closure. After a mean follow-up of 46.8 months (range 4–131 months), tumor recurrence was observed in 2 patients (20%), one of whom was treated with radiation and the other with chemotherapy. Both of these patients had previously undergone GTR of the IVC.

CONCLUSIONS

The 10 patients described in this report represent the largest number of patients with IVC treated using EEA for resection to date. EEA for resection of IVC is a safe and efficacious operative strategy that should be considered a surgical option in the treatment of this challenging subset of tumors.

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Edgar G. Ordóñez-Rubiano, Jonathan A. Forbes, Peter F. Morgenstern, Leopold Arko, Georgiana A. Dobri, Jeffrey P. Greenfield, Mark M. Souweidane, Apostolos John Tsiouris, Vijay K. Anand, Ashutosh Kacker and Theodore H. Schwartz

OBJECTIVE

Gross-total resection (GTR) of craniopharyngiomas (CPs) is potentially curative and is often the goal of surgery, but endocrinopathy generally results if the stalk is sacrificed. In some cases, GTR can be attempted while still preserving the stalk; however, stalk manipulation or devascularization may cause endocrinopathy and this strategy risks leaving behind small tumor remnants that can recur.

METHODS

A retrospective review of a prospective cohort of patients who underwent initial resection of CP using the endoscopic endonasal approach over a period of 12 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital, was performed. Postresection integrity of the stalk was retrospectively assessed using operative notes, videos, and postoperative MRI. Tumors were classified based on location into type I (sellar), type II (sellar-suprasellar), and type III (purely suprasellar). Pre- and postoperative endocrine function, tumor location, body mass index, rate of GTR, radiation therapy, and complications were reviewed.

RESULTS

A total of 54 patients who had undergone endoscopic endonasal procedures for first-time resection of CP were identified. The stalk was preserved in 33 (61%) and sacrificed in 21 (39%) patients. GTR was achieved in 24 patients (73%) with stalk preservation and 21 patients (100%) with stalk sacrifice (p = 0.007). Stalk-preservation surgery achieved GTR and maintained completely normal pituitary function in only 4 (12%) of 33 patients. Permanent postoperative diabetes insipidus was present in 16 patients (49%) with stalk preservation and in 20 patients (95%) following stalk sacrifice (p = 0.002). In the stalk-preservation group, rates of progression and radiation were higher with intentional subtotal resection or near-total resection compared to GTR (67% vs 0%, p < 0.001, and 100% vs 12.5%, p < 0.001, respectively). However, for the subgroup of patients in whom GTR was achieved, stalk preservation did not lead to significantly higher rates of recurrence (12.5%) compared with those in whom it was sacrificed (5%, p = 0.61), and stalk preservation prevented anterior pituitary insufficiency in 33% and diabetes insipidus in 50%.

CONCLUSIONS

While the decision to preserve the stalk reduces the rate of postoperative endocrinopathy by roughly 50%, nevertheless significant dysfunction of the anterior and posterior pituitary often ensues. The decision to preserve the stalk does not guarantee preserved endocrine function and comes with a higher risk of progression and need for adjuvant therapy. Nevertheless, to reduce postoperative endocrinopathy attempts should be made to preserve the stalk if GTR can be achieved.

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Jonathan A. Forbes, Matei Banu, Kurt Lehner, Malte Ottenhausen, Emanuele La Corte, Andrew F. Alalade, Edgar G. Ordóñez-Rubiano, Jeffrey P. Greenfield, Vijay K. Anand and Theodore H. Schwartz

OBJECTIVE

Epidermoid cysts (ECs) commonly extend to involve the ventral cisterns of the cranial base. When present, symptoms arise due to progressive mass effect on the brainstem and adjacent cranial nerves. Historically, a variety of open microsurgical approaches have been used for resection of ECs in this intricate region. In recent years, the endoscopic endonasal approach (EEA) has been proposed as an alternative corridor that avoids crossing the plane of the cranial nerves. To date, there is a paucity of data in the literature regarding the safety and efficacy of the EEA in the treatment of ECs of the ventral cranial base.

METHODS

The authors reviewed a prospectively acquired database of EEAs for resection of ECs over 8 years at Weill Cornell, NewYork-Presbyterian Hospital. All procedures were performed by the senior authors. Standardized clinical and radiological parameters were assessed before and after surgery. Statistical tests were used to determine the impact of previous surgery and tumor volume on extent of resection and recurrence as well as the method of closure on rate of CSF leak.

RESULTS

Between January 2009 and February 2017, 7 patients (4 males and 3 females; age range 16–70 years) underwent a total of 8 surgeries for EC resection utilizing the EEA. Transplanum and transclival extensions were performed in 3 and 5 patients, respectively. Methods of closure incorporated a gasket seal in 6 of 8 procedures and a nasoseptal flap in 7 of 8 procedures. Gross-total resection (GTR) was achieved in 43% of patients, and near-total resection (> 95%) was obtained in another 43%. Complications included diabetes insipidus (n = 2), postoperative CSF leak (n = 2), transient third cranial nerve palsy (n = 1), and epistaxis (n = 1). With a mean follow-up of 43.5 months, recurrence has been observed in 2 of 7 patients. In 1 case, reoperation for recurrence was required 71 months following the initial surgery. Use of the gasket-seal technique with nasoseptal flap coverage significantly correlated with the absence of postoperative CSF leakage (p = 0.018). GTR was achieved in 25% of the patients who had prior surgeries and in 50% of patients without previous resections. The mean volume of cysts in which GTR was achieved (4.3 ± 1.8 cm3) was smaller than that in which subtotal or near-total resection was achieved (12.2 ± 11 cm3, p = 0.134).

CONCLUSIONS

The EEA for resection of ECs of the ventral cranial base is a safe and effective operative strategy that avoids crossing the plane of the cranial nerves. In the authors’ experience, gasket-seal closure with nasoseptal flap coverage has been associated with a decreased risk of postoperative CSF leakage.

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Victor M. Lu, Kyle P. O’Connor, Benjamin T. Himes, Desmond A. Brown, Cody L. Nesvick, Ruby G. Siada, Toba N. Niazi, Jonathan Schwartz and David J. Daniels

OBJECTIVE

Glioblastoma (GBM) during infancy is rare, and the clinical outcomes of congenital GBM are not well understood. Correspondingly, the aim of this study was to present a long-term survivor case from the authors’ institution, and establish an integrated cohort of cases across the published literature to better understand the clinical course of this disease in this setting.

METHODS

The authors report the outcomes of an institutional case of congenital GBM diagnosed within the first 3 months of life, and performed a comprehensive literature search for published cases from 2000 onward for an integrated survival analysis. All cases were integrated into 1 cohort, and Kaplan-Meier estimations, Fisher’s exact test, and logistic regression were used to interrogate the data.

RESULTS

The integrated cohort of 40 congenital GBM cases consisted of 23 (58%) females and 17 (42%) males born at a median gestational age of 38 weeks (range 22–40 weeks). Estimates of overall survival (OS) at 1 month was 67%, at 1 year it was 59%, and at 10 years it was 45%, with statistically superior outcomes for subgroups in which patients survived to be treated by resection and chemotherapy. In the overall cohort, multivariable analysis confirmed resection (p < 0.01) and chemotherapy (p < 0.01) as independent predictors of superior OS. Gestational age > 38 weeks (p < 0.01), Apgar scores ≥ 7 at 5 minutes (p < 0.01), absence of prenatal hydrocephalus (p < 0.01), and vaginal delivery (p < 0.01) were associated with greater odds of surgical diagnosis versus autopsy diagnosis.

CONCLUSIONS

Congenital GBM can deviate from the expected poor prognosis of adult GBM in terms of OS. Both resection and chemotherapy confer statistically superior prognostic advantages in those patients who survive within the immediate postnatal period, and should be first-line considerations in the initial management of this rare disease.

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Nelson Moussazadeh, Charles Kulwin, Vijay K. Anand, Jonathan Y. Ting, Caryn Gamss, J. Bryan Iorgulescu, Apostolos John Tsiouris, Aaron A. Cohen-Gadol and Theodore H. Schwartz

OBJECT

The authors of this study sought to report the technique and early clinical outcomes of a purely endonasal endoscopic approach for resection of petroclival chondrosarcomas.

METHODS

Between 2010 and 2014, 8 patients (4 men and 4 women) underwent endonasal endoscopic operations to resect petroclival chondrosarcomas at 2 institutions. The patients' mean age was 44.8 years (range 30–64 years). One of the patients had previously undergone radiation therapy and another a staged craniotomy. Using volumetric software, an independent neuroradiologist assessed the extent of the resections on MRI scans taken immediately after surgery and at the 3-month follow-up. Immediate complications and control of symptoms were also recorded. In addition, the authors reviewed the current literature on surgical treatment of chondrosarcoma.

RESULTS

The mean preoperative tumor diameter and volume were 3.4 cm and 9.8 cm3, respectively. Six patients presented with cranial neuropathies. Endonasal endoscopic surgery achieved > 95% resection in 5 of the 8 patients and < 95% resection in the remaining 3 patients. One of the 6 neuropathies resolved, and the remaining 5 partially improved. One instance of postoperative CSF leakage required a reoperation for repair; no other complications associated with these operations were observed. All of the patients underwent adjuvant radiotherapy.

CONCLUSIONS

According to the authors' experience, the endoscopic endonasal route is a safe and effective approach for the resection of appropriately selected petroclival chondrosarcomas.