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1.  Efficacy and toxicity of second-course ophthalmic artery chemosurgery for retinoblastoma 
Ophthalmology  2015;122(5):1016-1022.
Objective
Assess the utility of second-course ophthalmic artery chemosurgery (OAC) for patients with intra-ocular retinoblastoma that recurred following prior ophthalmic artery chemosurgery. This study evaluates the efficacy and toxicity of second-course OAC.
Design
Single-arm, retrospective study of 29 eyes in 30 patients treated with second-course OAC at Memorial Sloan-Kettering Cancer Center between May 2006 and July 2013, with a median 25.9 months follow-up.
Participants
Retinoblastoma patients who underwent a course of OAC, with a minimum of 2 months of progression-free follow-up at monthly examinations, but who subsequently received additional OAC for recurrent tumor.
Methods
Efficacy- Kaplan-Meier survival estimates were generated and the Mantel-Cox test was used to compare curves. Toxicity- Electroretinogram (ERG) amplitudes were measured in response to 30-Hz photopic flicker stimulation before and after OAC treatment; systemic adverse events were graded according to CTCAE 4.0.
Main Outcome Measure
Efficacy- Ocular progression free survival, ocular event (enucleation, external beam radiation or intravitreal melphalan) free survival and ocular survival. Toxicity- Peak-to-peak comparisons between ERG studies before and after OAC treatment; CTCAE 4.0 graded systemic adverse events.
Results
50% of all recurrences were within 4.4 months and 90% were within 16 months of completion of first course OAC. The 2-year Kaplan-Meier ocular survival, event free survival and progression free survival estimates following second-course OAC were 82.8% (95% confidence interval [CI], 60.1–93.2%), 57.3% (95%CI, 36.1–73.7%) and 26.5% (95% confidence interval [CI], 11.0–45.0%), respectively. All eyes without vitreous seeding are progression free, while eyes with vitreous seeding were significantly associated with worse ocular survival following second- course OAC (p=0.03). Following second-course OAC, 90% of eyes had stable or improved electroretinogram responses. Of all evaluable cases, there was no increased risk of systemic toxicity during second course compared to initial course OAC.
Conclusions
Retinoblastoma eyes requiring second-course OAC following initial OAC treatment have good salvage rates and the treatment has an acceptable ocular and systemic toxicity profile. However, these eyes often require additional (third or fourth-course) OAC or other treatment modalities due to progression of disease after second-line OAC, particularly if vitreous seeds are present at the time of initial OAC failure.
Precis
Eyes with recurrent tumor following initial ophthalmic artery chemosurgery can be salvaged with second-course ophthalmic artery chemosurgery, although ocular survival is worse for eyes with vitreous seeds.
doi:10.1016/j.ophtha.2014.11.029
PMCID: PMC4994525  PMID: 25616769
2.  Simultaneous Bilateral Ophthalmic Artery Chemosurgery for Bilateral Retinoblastoma (Tandem Therapy) 
PLoS ONE  2016;11(6):e0156806.
Objective
Report on the 7-year experience with bilateral ophthalmic artery chemosurgery (OAC-Tandem therapy) for bilateral retinoblastoma.
Design
Retrospective, single institution study.
Subjects
120 eyes of 60 children with bilateral retinoblastoma treated since March 2008.
Methods
Retrospective review of all children treated at Memorial Sloan Kettering with bilateral ophthalmic artery chemosurgery (Melphalan, Carboplatin, Topotecan, Methotrexate) delivered in the same initial session to both naïve and previously treated eyes.
Main Outcome Measures
Ocular survival, metastatic disease, patient survival from metastases, second cancers, systemic adverse effects, need for transfusion of blood products, electroretinogram before and after treatment.
Results
116 eyes were salvaged (4 eyes were enucleated: 3 because of progressive disease, 1 family choice). Kaplan Meier ocular survival was 99.2% at one year, 96.9% at 2 and 3 years and 94.9% for years 4 through 7. There were no cases of metastatic disease or metastatic deaths with a mean follow-up of 3.01 years. Two children developed second cancers (both pineoblastoma) and one of them died. Transfusion of blood products was required in 3 cases (4 transfusions), 1.9%. Two children developed fever/neutropenia requiring hospitalization (0.95%). ERGs were improved in 21.6% and unchanged after treatment in 52.5% of cases (increase or decrease of less than 25μV).
Conclusions
Bilateral ophthalmic artery chemosurgery is a safe and effective technique for managing bilateral retinoblastoma-even when eyes are advanced bilaterally, and if both eyes have progressed after systemic chemotherapy. Ocular survival was excellent (94.9% at 8 years), there were no cases of of metastatic disease and no deaths from metastatic disease, but children remain at risk for second cancers. In 21.6% of cases ERG function improved. Despite using chemotherapy in both eyes in the same session, systemic toxicity was low.
doi:10.1371/journal.pone.0156806
PMCID: PMC4892546  PMID: 27258771
3.  Salvage/Adjuvant Brachytherapy After Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma 
Summary
The efficacy and toxicity of brachytherapy following ophthalmic artery chemo-surgery for retinoblastoma was investigated in 15 eyes of 15 patients. This combination was effective, even in eyes with vitreous seeding, and the toxicity appeared to be no worse than reported with other radiation/chemotherapy treatments for retinoblastoma. Brachytherapy represents a potentially valuable salvage treatment for patients with recurrent retinoblastoma following ophthalmic artery chemosurgery treatment.
Purpose
To evaluate the efficacy and toxicity of brachytherapy after ophthalmic artery chemo-surgery (OAC) for retinoblastoma.
Methods and Materials
This was a single-arm, retrospective study of 15 eyes in 15 patients treated with OAC followed by brachytherapy at (blinded institution) between May 1, 2006, and December 31, 2012, with a median 19 months' follow-up from plaque insertion. Outcome measurements included patient and ocular survival, visual function, and retinal toxicity measured by electroretinogram (ERG).
Results
Brachytherapy was used as adjuvant treatment in 2 eyes and as salvage therapy in 13 eyes of which 12 had localized vitreous seeding. No patients developed metastasis or died of retinoblastoma. The Kaplan-Meier estimate of ocular survival was 79.4% (95% confidence interval 48.7%-92.8%) at 18 months. Three eyes were enucleated, and an additional 6 eyes developed out-of-target volume recurrences, which were controlled with additional treatments. Patients with an ocular complication had a mean interval between last OAC and plaque of 2.5 months (SD 2.3 months), which was statistically less (P= .045) than patients without ocular complication who had a mean interval between last OAC and plaque of 6.5 months (SD 4.4 months). ERG responses from pre- versus postplaque were unchanged or improved in more than half the eyes.
Conclusions
Brachytherapy following OAC is effective, even in the presence of vitreous seeding; the majority of eyes maintained stable or improved retinal function following treatment, as assessed by ERG.
doi:10.1016/j.ijrobp.2013.06.2045
PMCID: PMC4843130  PMID: 23953635
4.  Impact of Operator and Site Experience on Outcomes after Angioplasty and Stenting in the SAMMPRIS Trial 
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.
Methods
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.
Results
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).
Conclusion
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.
doi:10.1136/neurintsurg-2012-010504
PMCID: PMC3652908  PMID: 22977278
Intracranial stenosis; angioplasty and stenting; clinical trial
5.  Intra-Arterial Chemotherapy (Ophthalmic Artery Chemosurgery) for Group D Retinoblastoma 
PLoS ONE  2016;11(1):e0146582.
Purpose
To report globe salvage rates, patient survival and adverse events of ophthalmic artery chemosurgery (OAC) for International Classification of Retinoblastoma (ICRB) group D retinoblastoma (naive and after prior failures).
Methods
Single institution retrospective review of all Group D eyes treated with OAC from 5/2006-12/2012. Patients were treated according to our previously-published techniques. Primary outcome was globe retention without need for external beam radiotherapy (EBRT). Demographics, prior treatments, OAC agents used, and adverse events were also recorded.
Results
112 group D eyes (103 patients) that underwent OAC were included (average follow-up was 34 months, range: 2–110 months). 47 eyes were treatment-naïve, 58 eyes received prior treatments elsewhere, and 7 young infants (7 eyes) underwent our published “bridge therapy” (single agent intravenous carboplatin) until old enough to undergo OAC. Median number of OAC sessions/eye was 3 (range 1–9). 110/112 eyes received intra-arterial melphalan, but only 31 eyes received melphalan alone. 43 eyes received carboplatin, and 78 eyes received topotecan (never as a single agent). 80/112 eyes received >1 drug over their treatment course, and 39 eyes received all three agents. 24 eyes (16 pretreated, 7 treatment-naïve, 1 bridge) failed treatment and required enucleation during the study period. Enucleation and EBRT were avoided in 88/112 eyes (78.6%; including 40/47 [85.1%] treatment-naïve eyes, 42/58 [72.4%] previously-treated eyes, and 6/7 eyes [85.7%] among bridge patients). By Kaplan-Meier survival analysis, globe salvage rate was 74% at 110 months among all patients, and 85% at 110 months in the treatment-naïve subgroup. Transient grade 3/4 neutropenia was more common in patients receiving OAC bilaterally. No child died of metastatic disease.
Conclusions
OAC is effective for curing group D retinoblastoma, achieving rates of globe salvage many times higher than systemic chemotherapy (10–47%), even in eyes that previously failed other treatments. OAC can be performed multiple times, using multiple agents, on one or both eyes of patients.
doi:10.1371/journal.pone.0146582
PMCID: PMC4710506  PMID: 26756643
6.  Advanced Unilateral Retinoblastoma: The Impact of Ophthalmic Artery Chemosurgery on Enucleation Rate and Patient Survival at MSKCC 
PLoS ONE  2015;10(12):e0145436.
Purpose
To report on the influence of ophthalmic artery chemosurgery (OAC) on enucleation rates, ocular and patient survival from metastasis and impact on practice patterns at Memorial Sloan Kettering for children with advanced intraocular unilateral retinoblastoma.
Patients and Methods
Single-center retrospective review of all unilateral retinoblastoma patients with advanced intraocular retinoblastoma treated at MSKCC between our introduction of OAC (May 2006) and December 2014. End points were ocular survival, patient survival from metastases and enucleation rates.
Results
156 eyes of 156 retinoblastoma patients were included. Primary enucleation rates have progressively decreased from a rate of >95% before OAC to 66.7% in the first year of OAC use to the present rate of 7.4%. The percent of patients receiving OAC has progressively increased from 33.3% in 2006 to 92.6% in 2014. Overall, ocular survival was significantly better in eyes treated with OAC in the years 2010–2014 compared to 2006–2009 (p = 0.023, 92.7% vs 68.0% ocular survival at 48 months). There have been no metastatic deaths in the OAC group but two patients treated with primary enucleation have died of metastatic disease.
Conclusion
OAC was introduced in 2006 and its impact on patient management is profound. Enucleation rates have decreased from over 95% to less than 10%. Our ocular survival rate has also significantly and progressively improved since May 2006. Despite treating more advanced eyes rather then enucleating them patient survival has not been compromised (there have been no metastatic deaths in the OAC group). In our institution, enucleation is no longer the most common treatment for advanced unilateral retinoblastoma.
doi:10.1371/journal.pone.0145436
PMCID: PMC4692433  PMID: 26709699
7.  Intra-Arterial Delivery of AAV Vectors to the Mouse Brain After Mannitol Mediated Blood Brain Barrier Disruption 
The delivery of therapeutics to neural tissue is greatly hindered by the blood brain barrier (BBB). Direct local delivery via diffusive release from degradable implants or direct intra-cerebral injection can bypass the BBB and obtain high concentrations of the therapeutic in the targeted tissue, however the total volume of tissue that can be treated using these techniques is limited. One treatment modality that can potentially access large volumes of neural tissue in a single treatment is intra-arterial (IA) injection after osmotic blood brain barrier disruption. In this technique, the therapeutic of interest is injected directly into the arteries that feed the target tissue after the blood brain barrier has been disrupted by exposure to a hyperosmolar mannitol solution, permitting the transluminal transport of the therapy. In this work we used contrast enhanced magnetic resonance imaging (MRI) studies of IA injections in mice to establish parameters that allow for extensive and reproducible BBB disruption. We found that the volume but not the flow rate of the mannitol injection has a significant effect on the degree of disruption. To determine whether the degree of disruption we observed with this method was sufficient for delivery of nanoscale therapeutics, we performed IA injections of an adeno-associated viral vector containing the CLN2 gene (AAVrh.10CLN2), which is mutated in the lysosomal storage disorder Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL). We demonstrated that IA injection of AAVrh.10CLN2 after BBB disruption can achieve widespread transgene production in the mouse brain after a single administration. Further, we showed that there exists a minimum threshold of BBB disruption necessary to permit the AAV.rh10 vector to pass into the brain parenchyma from the vascular system. These results suggest that IA administration may be used to obtain widespread delivery of nanoscale therapeutics throughout the murine brain after a single administration.
doi:10.1016/j.jconrel.2014.09.018
PMCID: PMC4268109  PMID: 25270115
Intra-arterial; neural drug delivery; MRI; blood brain barrier; adeno-associated virus
8.  Risk Factors for Severe Neutropenia following Intra-Arterial Chemotherapy for Intra-Ocular Retinoblastoma 
PLoS ONE  2014;9(10):e108692.
Purpose
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1371/journal.pone.0108692
PMCID: PMC4193762  PMID: 25303673
9.  Preoperative Embolization of Hypervascular Thoracic, Lumbar, and Sacral Spinal Column Tumors: Technique and Outcomes from a Single Center 
Interventional Neuroradiology  2013;19(3):377-385.
Summary
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.
PMCID: PMC3806015  PMID: 24070089
spine, tumor, preoperative embolization, surgery
10.  Electroretinogram Monitoring of Dose-Dependent Toxicity after Ophthalmic Artery Chemosurgery in Retinoblastoma Eyes: Six Year Review 
PLoS ONE  2014;9(1):e84247.
Purpose
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).
Methods
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.
Results
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.
Conclusion
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.
doi:10.1371/journal.pone.0084247
PMCID: PMC3896342  PMID: 24465398
11.  Death by Water: Precautionary Water Submersion for Intravitreal Injection of Retinoblastoma Eyes 
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.
doi:10.2174/1874364101408010007
PMCID: PMC4062941  PMID: 24949111
Cancer; chemotherapy; distilled water; fine needle aspiration; intravitreal injection; melphalan; retinoblastoma; water.
12.  Carboplatin +/− Topotecan Ophthalmic Artery Chemosurgery for Intraocular Retinoblastoma 
PLoS ONE  2013;8(8):e72441.
Purpose
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.
Methods
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.
Results
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.
Conclusion
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.
doi:10.1371/journal.pone.0072441
PMCID: PMC3749169  PMID: 23991112
13.  Combined, Sequential Intravenous and Intra-Arterial Chemotherapy (Bridge Chemotherapy) for Young Infants with Retinoblastoma 
PLoS ONE  2012;7(9):e44322.
Background
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
Procedure
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.
Results
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.
Conclusion
Bridge IV-IA chemotherapy was feasible and safe, and is a promising strategy to treat retinoblastoma in neonates and young infants.
doi:10.1371/journal.pone.0044322
PMCID: PMC3445577  PMID: 23028521
14.  Role of CT perfusion imaging in the diagnosis and treatment of vasospasm 
Imaging in medicine  2011;3(3):287-297.
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.
doi:10.2217/iim.11.19
PMCID: PMC3389822  PMID: 22773929
CT perfusion; delayed cerebral ischemia; digital subtraction angiography; subarachnoid hemorrhage; vasospasm
15.  Ophthalmic Artery Chemosurgery for Less Advanced Intraocular Retinoblastoma: Five Year Review 
PLoS ONE  2012;7(4):e34120.
Background
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).
Methodology/Principal Findings
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.
Conclusions/Significance
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.
doi:10.1371/journal.pone.0034120
PMCID: PMC3335846  PMID: 22545080
16.  Intraocular Hemorrhage After Intra-Arterial Chemotherapy for Retinoblastoma in Sickle Cell Trait 
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.
doi:10.2174/1874364101206010001
PMCID: PMC3267092  PMID: 22291865
Retinoblastoma; sickle cell; intra-arterial chemotherapy; enucleation.
17.  Thoraco-lumbar artery aneurysms associated with a metameric paraspinal lesion presenting with retroperitoneal hemorrhage: Endovascular management 
Background:
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.
Case Description:
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.
Conclusion:
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.
doi:10.4103/2152-7806.85978
PMCID: PMC3205498  PMID: 22059132
Arteriovenous malformation; endovascular embolization; metameric lesion; Onyx-34
18.  Endovascular management of distal anterior inferior cerebellar artery aneurysms: Report of two cases and review of the literature 
Background:
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.
Case Description:
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.
Conclusion:
Occlusion of the parent artery for the treatment of ruptured fusiform distal AICA aneurysms is effective but has significant neurological risks.
doi:10.4103/2152-7806.82577
PMCID: PMC3130468  PMID: 21748047
Anterior inferior cerebellar artery aneurysm; coil; endovascular therapy; meatal; parent artery occlusion; postmeatal
19.  Histopathologic Findings of Eyes Enucleated After Treatment with Chemosurgery for Retinoblastoma 
Introduction:
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.
Results:
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.
Conclusions:
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.
doi:10.2174/1874364101105010001
PMCID: PMC3052645  PMID: 21399766
Retinoblastoma; histopathology; chemosurgery.
20.  Interventional management for secondary intracranial extension of spontaneous cervical arterial dissection 
Background:
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.
Case Description:
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.
Conclusion:
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.
doi:10.4103/2152-7806.74092
PMCID: PMC3011101  PMID: 21206534
Cervical artery dissection; stent; transient ischemic attack

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