John R. Floyd

Cyclic sciatica from extrapelvic endometriosis affecting the sciatic nerve. Case report

Sciatic (catamenial) radiculopathy, waxing and waning with the menstrual cycle, is an uncommon condition typically caused by pelvic endometriosis affecting the lumbosacral plexus or proximal sciatic nerve. The authors describe a woman with catamenial sciatica caused by endometriosis affecting the sciatic nerve trunk in the upper thigh. Symptomatic with leg pain for 5 years, this patient developed gluteal atrophy and sensory loss and decreased strength in the L-5 dermatomyotome, a distribution confirmed by electromyography. Magnetic resonance imaging suggested thickening of the sciatic nerve at and distal to the sciatic notch. At operation the nerve showed extrinsic and intrinsic abnormality, proven to be endometriosis. Her symptoms improved, and she began gonadotropin-releasing hormone agonist therapy for further suppression. This very unusual case shows that endometriosis can affect the sciatic nerve over a range of territory inside and outside the pelvis, and that surgery must be appropriately directed to avoid negative exploration. Surgical decompression achieves good relief of symptoms, and medical therapy also allows sustained suppression of this disease.

Primary Central Nervous System Histiocytic Sarcoma Arising After Precursor B-Cell Acute Lymphoblastic Leukemia.

Abstract Histiocytic sarcomas (HSs) are rare malignant neoplasms derived from histiocytes that may be associated with other hematolymphoid neoplasms. Histiocytic sarcomas rarely occur in the CNS and have not previously been reported in conjunction with prior B-cell lymphoblastic leukemia. We report the case of a 23-year-old man who presented with primary CNS HS 7 years after achieving remission for precursor B-cell acute lymphoblastic leukemia (B-ALL). Molecular studies revealed clonal immunoglobulin heavy-chain (IGH) gene rearrangement within the HS, suggesting linkage to his previous B-ALL. Previously reported post-ALL HSs show a strong predilection for young males (male-to-female ratio, 20:1), whereas cases of primary CNS HS without previous ALL affected older adults with balanced sex predilection. The patients survival at 60 months exceeds expectations when compared with that of other reported cases of de novo primary CNS HS (n = 18) and post-ALL HS at all sites (n = 19). In addition, we discuss the potential relationship between B-ALL and HS posed by other authors.

A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases

Background: In this treatment planning study, we compare the plan quality and delivery parameters for the treatment of multiple brain metastases using 2 monoisocentric techniques: the Multiple Metastases Element from Brainlab and the RapidArc volumetric-modulated arc therapy from Varian Medical Systems. Methods: Eight patients who were treated in our institution for multiple metastases (3-7 lesions) were replanned with Multiple Metastases Element using noncoplanar dynamic conformal arcs. The same patients were replanned with the RapidArc technique in Eclipse using 4 noncoplanar arcs. Both techniques were designed using a single isocenter. Plan quality metrics (conformity index, homogeneity index, gradient index, and R50%), monitor unit, and the planning time were recorded. Comparison of the Multiple Metastases Element and RapidArc plans was performed using Shapiro-Wilk test, paired Student t test, and Wilcoxon signed rank test. Results: A paired Wilcoxon signed rank test between Multiple Metastases Element and RapidArc showed comparable plan quality metrics and dose to brain. Mean ± standard deviation values of conformity index were 1.8 ± 0.7 and 1.7 ± 0.6, homogeneity index were 1.3 ± 0.1 and 1.3 ± 0.1, gradient index were 5.0 ± 1.8 and 5.1 ± 1.9, and R50% were 4.9 ± 1.8 and 5.0 ± 1.9 for Multiple Metastases Element and RapidArc plans, respectively. Mean brain dose was 2.3 and 2.7 Gy for Multiple Metastases Element and RapidArc plans, respectively. The mean value of monitor units in Multiple Metastases Element plan was 7286 ± 1065, which is significantly lower than the RapidArc monitor units of 9966 ± 1533 (P < .05). Conclusion: For the planning of multiple brain lesions to be treated with stereotactic radiosurgery, Multiple Metastases Element planning software produced equivalent conformity, homogeneity, dose falloff, and brain V12 Gy but required significantly lower monitor units, when compared to RapidArc plans.

Osteolytic calvarial lesions as initial presentation of latent neurosyphilis

We report a patient with human immunodeficiency virus infection whose initial presentation of neurosyphilis was painful calvarial lesions. A literature search reveals seven previous cases of calvarial involvement in early acquired syphilis but none in patients diagnosed with neurosyphilis. This patient emphasizes the need to consider atypical infections when encountering skull lesions, especially in the setting of human immunodeficiency virus co-infection.

Clinical characteristics and treatment outcomes of patients with colorectal cancer who develop brain metastasis: a single institution experience

BACKGROUND The development of brain metastasis (BM) in patients with colorectal cancer (CRC) is a rare and late event. We sought to investigate the clinical characteristics, disease course and safety using biologic agents in our patients with CRC who develop brain metastases. METHODS A retrospective review of patients with CRC with brain metastases treated at our institution from 01/2005-01/2015 was performed. Survival analysis was performed using the Kaplan-Meier method. RESULTS Forty patients were included in the analysis. Median age was 55.5 years, 67.5% were males, and 28% had a KRAS mutation. Twenty-four percent were treatment-naive at the time of BM diagnosis. Patients had a median of two brain lesions. Sixty-five percent of the patients were treated with radiotherapy alone, 22.5% had both surgical resection and brain radiotherapy. Median overall survival was 3.2 months after development of BM. Overall survival was longer in patients who received combined modality local therapy compared to patients treated with surgical resection or radiotherapy alone. Patients who received systemic treatment incorporating biologics following development of BM had a median overall survival of 18.6 months. Overall, the administration of biologic agents was safe and well tolerated. CONCLUSIONS In summary, BM is an uncommon and late event in the natural history of metastatic CRC. The ability to deliver combined-modality local brain therapy as well as availability of more systemic therapy options appear to lead to improved outcomes.

Implant compositions for the unidirectional delivery of drugs to the brain

Abstract The overall objective of this study was to design and characterize the properties of a bioadhesive trilayer sustained-release implant device for the unidirectional local delivery of anticancer compounds to the brain following the removal of glioblastoma multiforme tumors. Using acetaminophen as a model drug compound, we compressed trilayer wafers that contained (i) a bioadhesive layer, (ii) a drug layer that contained a lipid and a pore-forming hydrophilic polymer, and (iii) a third layer comprising a lipid substance. To maintain a unidirectional pathway of drug release from these trilayer wafers, the edges and the surface lipophilic layer were coated with molten wax followed by cooling of the wafer. These wafers were subsequently heat cured to promote interlayer adhesion in the device. Polyethylene oxide was utilized both as the bioadhesive layer and the pore-forming hydrophilic polymer. Glyceryl behenate was employed as the lipid. The drug release properties of the trilayer wafer were a function of (i) the molecular weight and concentration of polyethylene oxide in the drug-containing lipid layer, (ii) the presence of the bioadhesive layer on the wafer, and (iii) the lipid coating applied to the top and sides of the delivery system. The unidirectional release of the drug occurred from the device through the bioadhesive layer, and zero-order release kinetics resulted over a 10-day period after a 3-day lag time. During this period, <10% of the drug had been released from the wafer. All of the drug was released by 21 days.

Surgical evacuation of acute subdural hematoma in octogenarians: a ten-year experience from a single trauma centerFunding

Abstract Background: Elderly patients presenting with an acute subdural hematoma (aSDH) have historically had unfavorable outcomes. Methods: We retrospectively reviewed patient records from 2005 through 2015 that were ≥80 years of age and underwent surgical evacuation of aSDH. Results: Thirty-four patients met inclusion criteria, with a mean age of 84 years (range 80–91). Glascow Outcome Scale (GOS) of 4–5 was deemed a good outcome and a GOS 1–3 was deemed to be a poor outcome. Six patients had good outcome at last follow up and 27 patients had poor outcome. Patients with a higher presenting Glascow Coma Scale (GCS) trended towards better outcome [(good: mean 13.1, median 14.5, IQR 12.5–15) vs. (poor: mean 9.6, median 10, IQR 6–14) p = 0.06]. Patients with a higher in-hospital post-operative GCS score had significantly better overall outcome than patients who left the hospital with a lower GCS score [(good: mean 14.5, median 14.5, IQR 14–15) vs. (poor: mean 8.4, median 9, IQR 4–11) p = 0.001]. Patients with a good outcome had a median aSDH thickness of 17mm (IQR 12.75–19.75) while patients with a poor outcome had a median thickness of 20mm (IQR 16–24.5); p = 0.17. In addition, patients with a good outcome had a median midline shift of 10mm (IQR 6–12.5), while patients with a poor outcome had a median midline shift of 14mm (IQR 10–20); p = 0.07. Conclusions: The prognosis for elderly patients with large aSDH remains poor, but a subset of patients can benefit from surgical intervention.

Endoscopic, Image-Guided, Transnasal Instillation of 32P for Recurrent Infrachiasmatic Cystic Craniopharyngioma

INTRODUCTION The neurovascular and anatomic relationships surrounding craniopharyngiomas, and their tending to recur despite any method of primary treatment, has characterized this tumor as an exigent and frustrating clinical entity. Various strategies have been developed to deal with recurrences which include radical re-resection, stereotactic or localized radiotherapy, cyst fenestration, marsupialization or stent placement, and intracavitary therapies such as bleomycin or radionucleotides. CASE REPORT We present a case where the patient had previously experienced a transsphenoidal resection followed by a pterional, microsurgical resection of her craniopharyngioma at an outside hospital. The second recurrence was cystic, and confined to the sella. We elected to proceed with a minimally invasive, transnasal endoscopic approach for the instillation of phosphorus 32 radionucleotide into the cyst. There were no complications, and the patient was discharged home on postoperative day one. At six months, there was no progression of the cyst. CONCLUSION While intracystic adionucleotide therapies have been utilized for primary and secondary treatment of craniopharyngioma, to our knowledge, this is the first report of the delivery of this therapy by an endoscopic transsphenoidal route.

Bone flap salvage in acute surgical site infection after craniotomy for tumor resection

Craniotomy surgical site infections are an inherent risk and dreaded complication for the elective brain tumor patient. Sequelae can include delays in resumption in adjuvant treatments for multiple surgeries if staged cranioplasty is pursued. Here, the authors review their experience in operative debridement of surgical site infections with single-stage reimplantation of the salvaged craniotomy bone flap. A prospectively maintained database of a single surgeon’s neuro-oncology patients from 2009 to 2017 (JRF) was queried to identify 11 patients with surgical site infection after craniotomy for tumor resection. All patients underwent a protocol of aggressive operative debridement including drilling the bone edges and intraoperative flap sterilization with single-stage reimplantation, followed by tailored-antibiotic therapy. Ten of the 11 patients with frankly contaminated bone flaps from surgical site infection were able to be salvaged in a single-stage procedure. Five of these patients underwent adjuvant chemotherapy and/or radiation without secondary complication. There was one treatment failure in a delayed fashion which required additional surgery for craniectomy; however, this occurred after adjuvant treatment was administered. Surgical debridement and bone flap salvage is safe and cost-effective in managing acute surgical site infections after craniotomy for tumors. Additionally, this practice is likely beneficial in expediting the resumption of cancer therapy.

Hypoxia-activated evofosfamide for treatment of recurrent bevacizumab-refractory glioblastoma: a phase I surgical study

Background Anti-angiogenic therapy is known to induce a greater degree of hypoxia, including in glioblastoma (GBM). Evofosfamide (Evo) is a hypoxia-activated prodrug which is reduced, leading to the release of the alkylating agent bromo-isophosphoramide mustard. We assessed the safety, tolerability, preliminary efficacy, and biomarkers of Evo plus bevacizumab (Bev) in Bev-refractory GBM. Methods Twenty-eight patients with Bev-refractory GBM were enrolled in a dose escalation study receiving from 240 mg/m2 (cohort 1) to 670 mg/m2 (cohort 4) of Evo every 2 weeks in combination with Bev. Patients deemed surgical candidates underwent a single dose of Evo or placebo with pimonidazole immediately prior to surgery for biomarker evaluation, followed by dose escalation upon recovery. Assessments included adverse events, response, and survival. Results Evo plus Bev was well tolerated up to and including the maximum dose of 670 mg/m2, which was determined to be the recommended phase II dose. Overall response rate was 17.4%, with disease control (complete response, partial response, and stable disease) observed in 14 (60.9%) of the 23 patients. The ratio of enhancement to non-enhancement was significant on log-rank analysis with time to progression (P = 0.023), with patients having a ratio of less than 0.37 showing a median progression-free survival of 98 days versus 56 days for those with more enhancement. Conclusions Evo plus Bev was well tolerated in patients with Bev-refractory GBM, with preliminary evidence of activity that merits further investigation.