Background and Purpose
To investigate the relationship between physician and site experience and the risk of 30-day hemorrhagic and ischemic strokes in the stenting arm of the SAMMPRIS trial.
Study records and an investigator survey were examined for physician and site-related factors, including: number of Wingspan and aneurysm stents submitted for credentialing, number of study procedures performed in SAMMPRIS, years in practice after training, primary specialty, and site enrollment. Bivariate and multivariate analyses were performed to determine if these factors were associated with the 30-day rate of cerebrovascular events after angioplasty and stenting.
Two hundred and thirteen patients underwent angioplasty alone (n=5) or angioplasty and stenting (n = 208) with study devices by 63 interventionists at 48 sites. For credentialing, the median number of Wingspan and similar aneurysm stent cases submitted by study interventionists were 10 and 6, respectively. Interventionists with higher numbers (≥ 10) of wingspan cases submitted for credentialing tended to have higher rates of 30-day events (19.0% versus 9.9%) than those with < 10 cases. High enrolling sites in the trial tended to have lower rates of hemorrhagic stroke (9.8% at sites enrolling < 12 patients versus 2.7% at sites enrolling ≥ 12 patients).
Interventionists credentialed with less Wingspan experience were not responsible for the high rate of peri-procedural stroke in SAMMPRIS. Hemorrhagic stroke may be related to low enrollment in the trial but not previous Wingspan experience.
Intracranial stenosis; angioplasty and stenting; clinical trial
Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥grade 3) neutropenia.
Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0.
54 cycles (29%) were associated with grade 3 (n = 43) or grade 4 (n = 11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33–12.73, p = 0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis.
Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted.
The existing literature on preoperative spine tumor embolization is limited in size of patient cohorts and diversity of tumor histologies. This report presents our experience with preoperative embolization of hypervascular thoracic, lumbar, and sacral spinal column tumors in the largest series to date.
We conducted a retrospective review of 228 angiograms and 188 pre-operative embolizations for tumors involving thoracic, lumbar and sacral spinal column. Tumor vascularity was evaluated with conventional spinal angiography and was graded from 0 (same as normal adjacent vertebral body) to 3 (severe tumor blush with arteriovenous shunting). Embolic materials included poly vinyl alcohol (PVA) particles and detachable platinum coils and rarely, liquid embolics. The degree of embolization was graded as complete, near-complete, or partial. Anesthesia records were reviewed to document blood loss during surgery.
Renal cell carcinoma (44.2%), thyroid carcinoma (9.2%), and leiomyosarcoma (6.6%) were the most common tumors out of a total of 40 tumor histologies. Hemangiopericytoma had the highest mean vascularity (2.6) of all tumor types with at least five representative cases followed by renal cell carcinoma (2.0) and thyroid carcinoma (2.0). PVA particles were used in 100% of cases. Detachable platinum coils were used in 51.6% of cases. Complete, near-complete, and partial embolizations were achieved in 86.1%, 12.7%, and 1.2% of all cases, respectively. There were no new post-procedure neurologic deficits or other complications with long-term morbidity. The mean intra-operative blood loss for the hypervascular tumors treated with pre-operative embolization was 1745 cc.
Preoperative embolization of hypervascular thoracic, lumbar, and sacral spine tumors can be performed with high success rates and a high degree of safety at high volume centers.
spine, tumor, preoperative embolization, surgery
To report electroretinogram responses of retinoblastoma children under anesthesia before and after treatment with chemotherapeutic drugs (melphalan, topotecan, carboplatin) delivery by ophthalmic artery chemosurgery (OAC).
A cohort study of 81 patients with retinoblastoma treated with OAC. All patients treated with OAC at our center through May 2012 for whom the requisite ERG data were available are included in the analysis. This study recorded the ERG 30 Hz flicker amplitude response changes from baseline, at 3 and 12 months following OAC treatment completion. Both univariate and multivariate linear regression models were evaluated, with generalized estimating equations to correct for correlations within patients. Independent numerical variables included maximum doses and cumulative doses of melphalan, topotecan and carboplatin.
By univariate analysis, both melphalan and topotecan appear to be associated with changes in ERG amplitude at both 3 and 12 months; but for the most part, these changes are minimal and likely clinically insignificant. By multivariate analysis, maximum and cumulative melphalan have a modest, temporary effect on the ERG amplitude change, which is apparent at 3 months but no longer evident at 12 months after completing treatment. By multivariate analysis, topotecan and carboplatin do not appear to adversely effect the change in ERG response.
Melphalan has the strongest, and carboplatin the weakest association with reduction in ERG response amplitudes; but for the most part, these changes are minimal and likely clinically insignificant. These conclusions apply only over the dose ranges used here, and should be applied with caution.
There is growing interest in intravitreal injections of chemotherapy for retinoblastoma. However, concerns for potential tumor seeding through the needle track has prompted the use of risk-reducing precautionary methods. Presented here is a novel technique, which can be easily replicated, requires minimal sophisticated equipment and with laboratory data supporting its concept. Sterile distilled water submersion for 3 minutes renders retinoblastoma cells nonviable and can be employed as a precautionary method following intravitreal injection in the technique described here.
Cancer; chemotherapy; distilled water; fine needle aspiration; intravitreal injection; melphalan; retinoblastoma; water.
Carboplatin administered systemically or periocularly can result in dramatic and prompt regression of retinoblastoma. However, both routes are rarely curative alone and have undesirable side effects. We aimed to assess the efficacy and toxicity of carboplatin +/− topotecan delivered by ophthalmic artery chemosurgery whereby chemotherapy is infused into the eye via the ophthalmic artery.
This retrospective, IRB-approved study investigated retinoblastoma patients whom received carboplatin +/− topotecan ophthalmic artery chemosurgery. Patient survival, ocular survival, hematologic toxicity, ocular toxicity, second cancer development and electroretinogram response were all evaluated.
57 carboplatin +/− topotecan infusions (of 111 total) were performed in 31 eyes of 24 patients. The remaining infusions were melphalan-containing. All patients were alive and no patient developed a second malignancy at a median follow up of 25 months. The Kaplan-Meier estimate of ocular survival at two years was 89.9% (95% confidence interval [CI], 82.1–97.9%) for all eyes. Grade 3 or 4 neutropenia developed in two patients and one patient developed metastatic disease. By univariate analysis, neither increasing maximum carboplatin/topotecan dose nor cumulative carboplatin/topotecan dose was associated with statistically significant reduction in the electroretinogram responses.
Carboplatin +/− topotecan infusions are effective for ophthalmic artery chemosurgery in retinoblastoma: they demonstrate low hematologic and ocular toxicity and no statistically significant influence on electroretinogram responses, and used in conjunction with melphalan-containing OAC, demonstrate excellent patient survival and satisfactory ocular survival.
Intra-arterial (IA) chemotherapy has more risks of procedural complications in neonates and young infants. For these reasons, we have developed a strategy of bridge intravenous single agent chemotherapy to postpone IA chemotherapy in these children
Neonates and young infants with retinoblastoma who required chemotherapy were treated with systemic carboplatin chemotherapy (18.7 mg/kg IV every 3–4 weeks) until they reached the age of 3 months and a weight of 6 Kg. If necessary, IA chemotherapy was subsequently performed at 4 weeks intervals. Efficacy was judged by tumor regression on ophthalmological examination. Retinal toxicity was judged by electroretinography.
Eleven children (19 eyes) were treated. All patients are alive and no patient has developed metastatic disease or second malignancies (mean follow-up 27 months, range 9–46 months). Intravenous carboplatin (median 2 cycles, range 1–5) combined with cryotherapy and laser was given to all children. This was effective for five eyes, which did not require IA chemotherapy. IA chemotherapy was administered to 14 eyes (median 3.5 cycles per eye, range 1 to 6). No radiation therapy was required. The Kaplan Meier estimate of ocular radiation-free survival was 94.7% at one year (95% confidence interval 68.1–99.2%). One eye was enucleated due to tumor progression. ERG showed no deterioration of retinal function.
Bridge IV-IA chemotherapy was feasible and safe, and is a promising strategy to treat retinoblastoma in neonates and young infants.
The current role of CT perfusion (CTP) imaging in the diagnosis and treatment of vasospasm in the setting of aneurysmal subarachnoid hemorrhage is discussed in this article, with specific attention directed towards defining the terminology of vasospasm and delayed cerebral ischemia. A commonly used CTP technique in clinical practice is described. A review of the literature regarding the usefulness of CTP for the diagnosis of vasospasm and its role in guiding treatment are discussed. Recent research advances in the utilization of CTP and associated ongoing challenges are also presented.
CT perfusion; delayed cerebral ischemia; digital subtraction angiography; subarachnoid hemorrhage; vasospasm
Ophthalmic artery chemosurgery (OAC) for retinoblastoma was introduced by us 5 years ago for advanced intraocular retinoblastoma. Because the success was higher than with existing alternatives and systemic side effects limited we have now treated less advanced intraocular retinoblastoma (Reese-Ellsworth (RE) I-III and International Classification Retinoblastoma (ICRB) B and C).
Retrospective review of 5 year experience in eyes with Reese Ellsworth (Table 1) I (7 eyes), II (6 eyes) or III (6 eyes) and/or International Classification (Table 2) B (19 eyes) and C (11 eyes) treated with OAC (melphalan with or without topotecan) introduced directly into the ophthalmic artery. Patient survival was 100%. Ocular event-free survival was 100% for Reese-Ellsworth Groups I, II and III (and 96% for ICRB B and C) at a median of 16 months follow-up. One ICRB Group C (Reese-Ellsworth Vb) eye could not be treated on the second attempt for technical reasons and was therefore enucleated. No patient required a port and only one patient required transfusion of blood products. The electroretinogram (ERG) was unchanged or improved in 14/19 eyes.
Ophthalmic artery chemosurgery for retinoblastoma that was Reese-Ellsworth I, II and III (or International Classification B or C) was associated with high success (100% of treatable eyes were retained) and limited toxicity with results that equal or exceed conventional therapy with less toxicity.
Massive intraocular hemorrhage developed in a child with advanced unilateral retinoblastoma after intrarterial treatment with Melphalan and Topotecan. The child tested positive for sickle cell trait. Sickle cell trait may predispose such children to slower vascular transit time, hypoxia, sickling and vascular occlusion caused by catheter induced decreased flow. Enucleation confirmed the ultrasound and selective angiogram findings in addition to a completely calcified tumor. Clinicians should be on the lookout for the association of sickle-cell disease/trait and intraocular hemorrhages after intraarterial chemotherapy to fully understand its clinical significance.
Retinoblastoma; sickle cell; intra-arterial chemotherapy; enucleation.
Retroperitoneal hemorrhage is a life-threatening condition. This is the first reported case of rupture of one of multiple thoraco-lumbar artery aneurysms associated with a metameric paraspinal vascular lesion.
A 77-year-old female patient presented to the emergency room with a new onset of left-sided low back pain shooting down the leg associated with weakness, numbness, and inability to walk. On physical examination, there was a notable left paraspinal swelling with a harsh bruit audible in the same area, left flank ecchymosis and a positive straight leg raising test. A computed tomography (CT) scan showed a large retroperitoneal hematoma. Digital subtraction angiography showed a large left paraspinal high-flow arteriovenous lesion, with large arterial aneurysms of the left T11, T12, and L1 segmental arteries. The patient was successfully treated with endovascular aneurysm embolization using coils and Onyx-34. Six months following the procedure, the patient had fully recovered, and a follow-up angiogram showed no residual or recurrent aneurysms.
Thoraco-lumbar artery aneurysms have never previously been described in association with a metameric paraspinal vascular malformation. We report a case of retroperitoneal hemorrhage due to rupture of one of several high-flow artery aneurysms of a paraspinal arteriovenous malformation (AVM). The diagnosis was made on CTA, MRI, and angiography, and the lesion was successfully treated by transarterial embolization.
Arteriovenous malformation; endovascular embolization; metameric lesion; Onyx-34
Aneurysms of the anterior inferior cerebellar artery (AICA), especially those located in the distal portion of the AICA, are rare. There are few reported cases treated with surgery or endovascular embolization.
We report two cases of fusiform distal AICA aneurysms presenting with subarachnoid hemorrhage. Parent artery occlusion with coils and n-butyl cyanoacrilate (n-BCA) resulted in complete aneurysm occlusion and prevented rebleeding. Both patients presented postprocedure neurological deficits, but have made a good recovery at 4 and 10 months, respectively.
Occlusion of the parent artery for the treatment of ruptured fusiform distal AICA aneurysms is effective but has significant neurological risks.
Anterior inferior cerebellar artery aneurysm; coil; endovascular therapy; meatal; parent artery occlusion; postmeatal
Intra-arterial chemotherapy (chemosurgery) for the treatment of retinoblastoma has been performed more than 1600 times (more than 1400 times in Japan and 200 times in New York) over the past 20 years.Despite this treatment’s success some eyes cannot be saved and require enucleation. Here we report the histopathologic findings of the remaining intraocular tumor of eyes that were enucleated following treatment that included chemosurgery in New York City.
Materials and Methodology:
Independent histopathologic review of the enucleated eyes was correlated with the clinical findings that prompted enucleation.
Between May 1, 2006 and April 30, 2009, 56 eyes received chemosurgery at our institution, and 10 of these were enucleated subsequently. All were Reese Ellsworth Group 5 at enucleation. Of the 21 eyes that were treated with chemosurgery as the primary treatment, 1 (5%) was enucleated subsequently; its histopathology revealed residual non-necrotic, non-calcified tumor. Of the 34 eyes treated with chemosurgery after other treatments, 9 (24%) were enucleated, and 5 of these eyes contained non-calcified, non-necrotic tumor. None was enucleated for complications of chemosurgery. All patients were alive and free of metastatic disease as of September 2009.
A significant number of eyes with advanced intraocular retinoblastoma avoided enucleation as a result of chemosurgery. The rate of eyes that were enucleated was higher when chemosurgery was the secondary rather than the primary treatment. Of the eight eyes enucleated for progressive disease six had non-necrotic, non-calcified tumor cells.
Retinoblastoma; histopathology; chemosurgery.
Spontaneous cervical artery dissection (sCAD) is an important etiology of stroke and subarachnoid hemorrhage (SAH) in young patients. Anticoagulation and platelet antiaggregant medications are the treatment of choice, while the indications of endovascular treatment are still to be defined.
We report two cases of medically refractory sCAD with intracranial extension treated successfully with multiple intra and extracranial stents. The patients were evaluated at 4 years and 1-year follow-up.
Progressive, spontaneous cervical artery dissection with intracranial extension despite adequate medical therapy is rare and associated with worse prognosis. Given the rapid evolution of interventional technology and techniques, if we are better able to predict the cohort of patients that fail medical management, earlier endovascular therapy may be considered.
Cervical artery dissection; stent; transient ischemic attack