Late Effects After Radiotherapy for Childhood Low-grade Glioma.

OBJECTIVES: This single-institution report describes long-term disease control and late effects in pediatric patients with low-grade glioma (LGG) following radiotherapy (RT). MATERIALS AND METHODS: Twenty-nine pediatric patients with LGG were treated with photon-based RT from 1970 to 2004 (mean age at time of RT, 9.8 y; range, 0.6 to 19 y). One patient underwent gross total resection, 25 underwent subtotal resection or biopsy, and 3 were treated based on radiographic characteristics alone. Three patients underwent chemotherapy before RT. The median RT dose was 54 Gy (range, 40 to 55 Gy). RESULTS: The median follow-up was 17.8 years (range, 1.6 to 36.8 y) for all patients and 19.9 years (range, 1.6 to 36.8 y) for all living patients. The 5-, 10-, and 20-year local control and progression-free survival rates were equivalent at 82%, 74%, and 63%, respectively. The 5-, 10-, and 20-year cause-specific survival and overall survival rates were equivalent at 89%, 85%, and 58%, respectively. On univariate analysis, age below 4 years during treatment was associated with significantly inferior local control (P=0.0067), cause-specific survival (P=0.0021), and overall survival (P=0.0021). Of the 23 survivors analyzed for late toxicity, 15 (65%) developed grade 3+ toxicity. The most common Common Terminology Criteria for Adverse Events grade 3 toxicity (30% of survivors) was serious cognitive disability. Four patients (14%) died secondary to treatment complications, all occurring over a decade after completing RT. CONCLUSIONS: Over half of children diagnosed with LGG survive >20 years after RT; this report reveals the chronicity of toxicity beyond the typically reported follow-up. Our findings inform the therapeutic ratio of RT in this disease and may help guide late-effect screening recommendations.

Brainstem angiocentric glioma: report of 2 cases.

Angiocentric glioma is a rare tumor that was recognized by the WHO Classification of Tumours of the Central Nervous System as a distinct clinicopathological entity in 2007. Since this initial description, the vast majority of cases of angiocentric glioma reported in the literature have involved tumors of the cerebral hemispheres. To date, only 1 case of angiocentric glioma arising from the posterior midbrain has been reported. The authors present the cases of 2 pediatric patients who were found to have brainstem angiocentric gliomas. The clinical course, radiological and pathological features, treatment, and follow-up are described. The first case is one of a 5-year-old girl who presented with double vision, headache, and nausea and was found to have a midbrain lesion with pathological features consistent with angiocentric glioma. She was treated with resection and endoscopic third ventriculostomy (ETV), followed by close observation and serial neuroimaging. The second case is one of a 6-year-old boy who presented with progressive mouth drooping and problems with balance. He was found to have a pontine lesion with pathological features consistent with angiocentric glioma. This patient was treated with ETV, followed by close observation and serial neuroimaging. This report includes 6 and 1.5 years of follow-up of the patients, respectively. While there are limited data regarding the prognosis or long-term management of patients with brainstem angiocentric gliomas, the cases described in this report suggest an indolent course for this tumor, similar to the course of angiocentric gliomas located in the cerebral hemispheres.

Functional Subclone Profiling for Prediction of Treatment-Induced Intratumor Population Shifts and Discovery of Rational Drug Combinations in Human Glioblastoma.

PURPOSE: Investigation of clonal heterogeneity may be key to understanding mechanisms of therapeutic failure in human cancer. However, little is known on the consequences of therapeutic intervention on the clonal composition of solid tumors. EXPERIMENTAL DESIGN: Here, we used 33 single cell-derived subclones generated from five clinical glioblastoma specimens for exploring intra- and interindividual spectra of drug resistance profiles in vitro In a personalized setting, we explored whether differences in pharmacologic sensitivity among subclones could be employed to predict drug-dependent changes to the clonal composition of tumors. RESULTS: Subclones from individual tumors exhibited a remarkable heterogeneity of drug resistance to a library of potential antiglioblastoma compounds. A more comprehensive intratumoral analysis revealed that stable genetic and phenotypic characteristics of coexisting subclones could be correlated with distinct drug sensitivity profiles. The data obtained from differential drug response analysis could be employed to predict clonal population shifts within the naïve parental tumor in vitro and in orthotopic xenografts. Furthermore, the value of pharmacologic profiles could be shown for establishing rational strategies for individualized secondary lines of treatment. CONCLUSIONS: Our data provide a previously unrecognized strategy for revealing functional consequences of intratumor heterogeneity by enabling predictive modeling of treatment-related subclone dynamics in human glioblastoma. Clin Cancer Res; 23(2); 562-74. ©2016 AACR.

Long-term growth and alignment after occipitocervical and atlantoaxial fusion with rigid internal fixation in young children.

OBJECT The long-term consequences of atlantoaxial (AA) and occipitocervical (OC) fusion and instrumentation in young children are unknown. Anecdotal reports have raised concerns regarding altered growth and alignment of the cervical spine after surgical intervention. The purpose of this study was to determine the long-term effects of these surgeries on the growth and alignment of the maturing spine. METHODS A multiinstitutional retrospective chart review was conducted for patients less than or equal to 6 years of age who underwent OC or AA fusion with rigid instrumentation at 9 participating centers. All patients had at least 3 years of clinical and radiographic follow-up data and radiographically confirmed fusion. Preoperative, immediate postoperative, and most recent follow-up radiographs and/or CT scans were evaluated to assess changes in spinal growth and alignment. RESULTS Forty children (9 who underwent AA fusion and 31 who underwent OC fusion) were included in the study (mean follow-up duration 56 months). The mean vertical growth over the fused levels in the AA fusion patients represented 30% of the growth of the cervical spine (range 10%-50%). Three different vertical growth patterns of the fusion construct developed among the 31 OC fusion patients during the follow-up period: 1) 16 patients had substantial growth (13%-46% of the total growth of the cervical spine); 2) 9 patients had no meaningful growth; and 3) 6 patients, most of whom presented with a distracted atlantooccipital dislocation, had a decrease in the height of the fused levels (range 7-23 mm). Regarding spinal alignment, 85% (34/40) of the patients had good alignment at follow-up, with straight or mildly lordotic cervical curvatures. In 1 AA fusion patient (11%) and 5 OC fusion patients (16%), we observed new hyperlordosis (range 43°-62°). There were no cases of new kyphosis or swan-neck deformity, evidence of subaxial instability, or unintended subaxial fusion. No preoperative predictors of these growth patterns or alignment were evident. CONCLUSIONS These results demonstrate that most young children undergoing AA and OC fusion with rigid internal fixation continue to have good cervical alignment and continued growth within the fused levels during a prolonged follow-up period. However, some variability in vertical growth and alignment exists, highlighting the need to continue close long-term follow-up.

Embryonal tumor with multilayered rosettes of the fourth ventricle: case report.

Embryonal tumor with multilayered rosettes (ETMR) is a recently described pathological entity. These primitive central nervous system tumors harbor amplification of the 19q13.42 locus and resultant overexpression of the LIN28A protein. Although the WHO currently recognizes 3 distinct histopathological entities-embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma-recent studies indicate that these tumors have a common molecular profile and clinical course and that they are now classified as a single entity. Here the authors present a case of ETMR located in the fourth ventricle in a 12-month-old boy. The histopathology featured areas of neuropil-like stroma and highly cellular foci with characteristic multilayered rosettes. The authors discuss the clinical, radiological, and histopathological findings in this case and compare them with data in previously published cases in the literature. A review of studies assessing the molecular mechanisms underlying these tumors is also presented.

Local control in non-metastatic medulloblastoma.

BACKGROUND: A single-institution review of long-term outcomes and factors affecting local control (LC) following radiotherapy for non-metastatic medulloblastoma. MATERIAL AND METHODS: From 1963 to 2008, 50 children (median age, 7.3 years; range 1.2-18.5) with stage M0 medulloblastoma were treated with radiotherapy; half underwent a gross total resection (no visible residual tumor) or near-total resection (< 1.5 cm(3) of gross disease remaining after resection). Median craniospinal dose was 28.8 Gy (range 21.8-38.4 Gy). Median total dose to the posterior fossa was 54.3 Gy (range 42.4-64.8 Gy). Eighteen patients (36%) received chemotherapy as part of multimodality management, including 11 who received concurrent chemotherapy. RESULTS: Median follow-up was 15.7 years (range 0.3-44.4 years) for all patients and 26.6 years (range 7.3-44.4 years) for living patients. The 10-year overall survival, cancer-specific survival, and progression-free survival rates were 65%, 65%, and 69%. The 10-year LC rate was 84% and did not significantly change across eras. Four percent of patients experienced local progression five years after treatment. On univariate analysis, chemotherapy and overall duration of radiotherapy ≤ 45 days were associated with improved LC. Patients receiving chemotherapy had a 10-year 100% LC rate versus 76% in patients not receiving chemotherapy (p = 0.0454). When overall radiotherapy treatment lasted ≤ 45 days, patients experienced a superior 95% 10-year LC rate (vs. 73% in patients treated > 45 days; p = 0.0419). Three patients (6%) died from treatment complications, including radionecrosis/cerebellar degeneration, severe cerebral edema leading to herniation, and secondary malignancy. CONCLUSIONS: While we cannot draw definitive conclusions given the retrospective nature of our study, our long-term data suggest that reductions in craniospinal dose and boost target volume to reduce toxicity have not compromised disease control in the modern era. Our data also support analyses that implicate duration of radiotherapy, rather than interval between surgery and radiotherapy, as a factor in LC. Chemotherapy in multimodality management of medulloblastoma may have an underappreciated role in improving LC rates.

Ogilvie's syndrome after pediatric spinal deformity surgery: successful treatment with neostigmine.

Ogilvie's syndrome is a rare and potentially fatal disease that can easily be mistaken for postoperative ileus. Also known as acute colonic pseudo-obstruction, early recognition and diagnosis of the syndrome allows for treatment prior to bowel perforation and requisite abdominal surgery. The authors report a case of Ogilvie's syndrome following spinal deformity correction and tethered cord release in an adolescent who presented with acute abdominal distension, nausea, and vomiting on postoperative Day 0. The patient was initially diagnosed with adynamic ileus and treated conservatively with bowel rest, reduction in narcotic dosage, and a regimen of stool softeners, laxatives, and enemas. Despite this treatment, her clinical course failed to improve, and she demonstrated significant colonic distension radiographically. Intravenous neostigmine was administered as a bolus with a rapid and dramatic response. This case is the first reported instance of neostigmine use for Ogilvie's syndrome treatment following a pediatric neurosurgical operation.

Late toxicity following craniospinal radiation for early-stage medulloblastoma.

BACKGROUND: The purpose of this study is to review late toxicity following craniospinal radiation for early-stage medulloblastoma. MATERIAL AND METHODS: Between 1963 and 2008, 53 children with stage M0 (n = 50) or M1 (n = 3) medulloblastoma were treated at our institution. The median age at diagnosis was 7.1 years (range 1.2-18.5). The median craniospinal irradiation (CSI) dose was 28.8 Gy (range 21.8-38.4). The median total dose, including boost, was 54 Gy (range 42.4-64.8 Gy). Since 1963, the CSI dose has been incrementally lowered and the high-risk boost volume reduced. Twenty-one patients (40%) received chemotherapy in their initial management, including 12 who received concurrent chemotherapy. Late sequelae were evaluated by analyzing medical records and conducting phone interviews with surviving patients and/or care-takers. Complications were graded using the NCI Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: The median follow-up for all patients was 15.4 years (range 0.4-44.4) and for living patients it was 24 years (range 5.6-44.4). The overall survival, cause-specific survival, and progression-free survival rates at 10 years were 67%, 67%, and 71%, respectively. Sixteen patients (41% of patients who survived five years or more) developed grade 3 + toxicity; 15 of these 16 patients received a CSI dose > 23.4 Gy. The most common grade 3 + toxicities for long-term survivors are hearing impairment requiring intervention (20.5%) and cognitive impairment (18%) prohibiting independent living. Four patients developed secondary (non-skin) malignancies, including three meningiomas, one rhabdomyosarcoma, and one glioblastoma multiforme. Three patients (5.6%) died from treatment complications, including radionecrosis, severe cerebral edema, and fatal secondary malignancy. CONCLUSION: Ongoing institutional and cooperative group efforts to minimize radiation exposure are justified given the high rate of serious toxicity observed in our long-term survivors. Follow-up through long-term multidisciplinary clinics is important and warranted for all patients exposed to radiotherapy in childhood.

Anticancer effects of niclosamide in human glioblastoma.

PURPOSE: Glioblastoma is a highly malignant, invariably fatal brain tumor for which effective pharmacotherapy remains an unmet medical need. EXPERIMENTAL DESIGN: Screening of a compound library of 160 synthetic and natural toxic substances identified the antihelmintic niclosamide as a previously unrecognized candidate for clinical development. Considering the cellular and interindividual heterogeneity of glioblastoma, a portfolio of short-term expanded primary human glioblastoma cells (pGBM; n = 21), common glioma lines (n = 5), and noncancer human control cells (n = 3) was applied as a discovery platform and for preclinical validation. Pharmacodynamic analysis, study of cell-cycle progression, apoptosis, cell migration, proliferation, and on the frequency of multipotent/self-renewing pGBM cells were conducted in vitro, and orthotopic xenotransplantation was used to confirm anticancer effects in vivo. RESULTS: Niclosamide led to cytostatic, cytotoxic, and antimigratory effects, strongly reduced the frequencies of multipotent/self-renewing cells in vitro, and after exposure significantly diminished the pGBMs' malignant potential in vivo. Mechanism of action analysis revealed that niclosamide simultaneously inhibited intracellular WNT/CTNNB1-, NOTCH-, mTOR-, and NF-κB signaling cascades. Furthermore, combinatorial drug testing established that a heterozygous deletion of the NFKBIA locus in glioblastoma samples could serve as a genomic biomarker for predicting a synergistic activity of niclosamide with temozolomide, the current standard in glioblastoma therapy. CONCLUSIONS: Together, our data advocate the use of pGBMs for exploration of compound libraries to reveal unexpected leads, for example, niclosamide that might be suited for further development toward personalized clinical application.

Temporary percutaneous pedicle screw fixation for treatment of thoracolumbar injuries in young adults.

OBJECTIVE: Bone-only injuries of the spine, including Chance fractures, are commonly managed nonoperatively. However, selected patients may benefit from surgical stabilization. In this report, the authors describe a method of temporary internal fixation with percutaneous pedicle screws for patients with intractable pain and thoracolumbar fractures. METHODS: We reviewed the medical records and imaging studies of three patients 17 to 21 years old with thoracolumbar fractures that were treated with temporary internal fixation. The patients had bone-only injuries without a major deformity. Additionally, they had severe pain that was uncontrolled with parenteral pain medications and prevented mobilization with traditional external bracing. For fixation, pedicle screws were placed percutaneously in the level above and below the fracture. No arthrodesis was performed. After 6 months, fracture healing was evaluated radiographically. Once confirmed, the instrumentation was removed. Outcomes examined include length of stay, pain control, time to ambulation, and fracture healing. RESULTS: Three patients were included in the review, ages 17 to 21 (mean 18.7) years. Two patients had classic Chance fractures, and the third had bilateral pars fractures with a compression fracture at the same level. All patients had severe pain despite bracing. Postoperatively, all patients had significant pain reduction that facilitated rapid mobilization. At 6 months after surgery, fracture healing was verified with radiographic imaging and the instrumentation was removed. There were no complications. CONCLUSIONS: Temporary internal bracing of bone-only thoracolumbar fractures in young adults is a safe and effective treatment strategy in selected patients. This procedure provides rapid pain control and early mobilization without sacrificing any spinal motion segments.

Occipitocervicothoracic stabilization in pediatric patients.

OBJECT: Although rarely encountered, pediatric patients with severe cervical spine deformities and instability may occasionally require occipitocervicothoracic instrumentation and fusion. This case series reports the experience of 4 pediatric centers in managing this condition. Occipitocervical fixation is the treatment of choice for craniocervical instability that is symptomatic or threatens neurological function. In children, the most common distal fixation level with modern techniques is C-2. Treated patients maintain a significant amount of neck motion due to the flexibility of the subaxial cervical spine. Distal fixation to the thoracic spine has been reported in adult case series. This procedure is to be avoided due to the morbidity of complete loss of head and neck motion. Unfortunately, in rare cases, the pathological condition or highly aberrant anatomy may require occipitocervical constructs to include the thoracic spine. METHODS: The authors identified 13 patients who underwent occipitocervicothoracic fixation. Demographic, radiological, and clinical data were gathered through retrospective review of patient records from 4 institutions. RESULTS: Patients ranged from 1 to 14 years of age. There were 7 girls and 6 boys. Diagnoses included Klippel-Feil, Larsen, Morquio, and VATER syndromes as well as postlaminectomy kyphosis and severe skeletal dysplasia. Four patients were neurologically intact and 9 had myelopathy. Five children were treated with preoperative traction prior to instrumentation; 5 underwent both anterior and posterior spinal reconstruction. Two patients underwent instrumentation beyond the thoracic spine. Allograft was used anteriorly, and autologous rib grafts were used in the majority for posterior arthrodesis. Follow-up ranged from 0 to 43 months. Computed tomography confirmed fusion in 9 patients; the remaining patients were lost to follow-up or had not undergone repeat imaging at the time of writing. Patients with myelopathy either improved or stabilized. One child had mild postoperative unilateral upper-extremity weakness, and a second child died due to a tracheostomy infection. All patients had severe movement restriction as expected. CONCLUSIONS: Occipitocervicothoracic stabilization may be employed to stabilize and reconstruct complex pediatric spinal deformities. Neurological function can be maintained or improved. The long-term morbidity of loss of cervical motion remains to be elucidated.

Intracranial ependymomas treated with radiotherapy: long-term results from a single institution.

The purpose of the study is to report long-term outcomes following surgery and radiotherapy for intracranial ependymoma. We retrospectively reviewed the medical records of patients treated with radiotherapy for localized intracranial ependymomas from 1964 to 2006. Patients with subependymomas and ependymoblastomas, and those undergoing re-irradiation, were excluded. Our study population is 44 patients: 37 infratentorial lesions, 7 supratentorial. All patients had postoperative radiotherapy; most received sub-total resection and one-third received gross total resection. Most patients received local radiotherapy alone (median tumor dose 55 Gy); one-quarter received craniospinal irradiation (median dose 35 Gy). The 5- and 10-year local-control rates for all patients were 60 and 46%, respectively; 23% of local recurrences occurred after 5 years. Ninety-five percent of the patients recurred at the primary site; 5% had spinal seeding with no evidence of disease at the primary site. No patient who received craniospinal irradiation recurred in the spine. The 5- and 10-year disease-free survival and overall-survival rates for all patients were 60 and 42% and 57 and 43%, respectively. On multivariate analysis, age ≥18 years, gross total resection and infratentorial site were associated with improved local control. No patient with continuous local control had grade 4 or 5 toxicities; 27% of patients had grade 2 or 3 toxicities. One patient developed a radiation-induced meningioma >20 years after radiotherapy. Maximal safe resection followed by adjuvant radiotherapy provided local control in one-half of patients at 10 years. Age, extent of surgery, and location were identified as major independent prognostic factors in patients with intracranial ependymomas.

Recombinant human bone morphogenetic protein-2 as an adjunct for spine fusion in a pediatric population.

BACKGROUND/AIMS: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is responsible for multiple different signaling processes including positive effects on bone formation and fusion. In 2002, rhBMP-2 was approved for use in anterior lumbar spinal fusion by the Food and Drug Administration. Since that time, rhBMP-2 use for spinal fusion has become widespread. The use of rh-BMP2 for pediatric spinal fusion, however, has not been widely reported. We report the experience of the use of rhBMP-2 for pediatric spinal fusion at the University of Florida. METHODS: Data on patients under the age of 18 years who underwent spinal fusion with rhBMP-2 as an adjunct were retrospectively collected. Of these, 17 met the inclusion criteria and were reviewed. Two patients did not have adequate postoperative imaging. Fifteen patients were included in the final review. RESULTS: All 15 patients showed osseous fusion. Complications included one CSF leak and one wound infection, one misplaced screw requiring revision, and one case of adjacent segment kyphosis requiring extension of the original construct. CONCLUSION: rhBMP-2 is a successful adjunct for fusion in pediatric patients. Many of these patients had congenital defects that historically decrease fusion rates. rhBMP-2 appears safe and has an associated high rate of osseous fusion.

Spinal and paraspinal Ewing tumors.

PURPOSE: To perform a review of the 40-year University of Florida experience treating spinal and paraspinal Ewing tumors. PATIENTS AND METHODS: A total of 27 patients were treated between 1965 and 2007. For local management, 21 patients were treated with radiotherapy (RT) alone and 6 with surgery plus RT. All patients with metastatic disease were treated with RT alone. The risk profiles of each group were otherwise similar. The median age was 17 years, and the most frequent subsite was the sacral spine (n = 9). The median potential follow-up was 16 years. RESULTS: The 5-year actuarial overall survival, cause-specific survival, and local control rate was 62%, 62%, and 90%, respectively. For the nonmetastatic subset (n = 22), the 5-year overall survival, cause-specific survival, and local control rate was 71%, 71%, and 89%, respectively. The local control rate was 84% for patients treated with RT alone vs. 100% for those treated with surgery plus RT. Patients who were >14 years old and those who were treated with intensive therapy demonstrated superior local control. Of 9 patients in our series with Frankel C or greater neurologic deficits at presentation, 7 experienced a full recovery with treatment. Of the 27 patients, 37% experienced Common Toxicity Criteria Grade 3 or greater toxicity, including 2 deaths from sepsis. CONCLUSION: Aggressive management of spinal and paraspinal Ewing tumors with RT with or without surgery results in high toxicity but excellent local control and neurologic outcomes. Efforts should be focused on identifying disease amenable to combined modality local therapy and improving RT techniques.

Aggressive surgical management of patients with Chiari II malformation and brainstem dysfunction.

BACKGROUND/AIMS: Chiari II malformation represents a group of developmental abnormalities involving the caudal displacement of the cervicomedullary junction, pons, fourth ventricle, and medulla. This constellation of malformations is strongly associated with myelomeningocele (MM) and is a known cause of neurologic deterioration in older MM patients. We describe the evaluation and management of 4 adult MM patients who presented with brainstem compression and a retroflexed odontoid who were subject to aggressive surgical management including occipitocervical (OC) fusion with good clinical results. METHODS: Four MM patients who underwent OC fusion for new-onset brainstem dysfunction and myelopathy were identified in the practice of the principal investigator (D.W.P.) from 2003 to 2008. RESULTS: The initial evaluation of these patients included consideration of other diagnoses, such as hydrocephalus due to shunt malfunction and tethered cord. These patients were treated with aggressive surgical management. In some cases, multiple surgeries were performed. All 4 patients were treated with cervical decompression and OC fixation and initially had good outcomes. No patients required transoral decompression. Three of the 4 had stable improvement at their last follow-up appointment (mean follow-up of 9 months). CONCLUSION: Late deterioration in older MM patients may be secondary to brainstem or cervical spinal cord compression from ventral odontoid compression and Chiari II malformation, hydrocephalus, hydromyelia, or tethered cord. These patients may benefit from more than one surgery. Posterior decompression and OC fusion can avoid a morbid transoral odontoid resection, greatly improve patients' symptoms and prevent further neurologic decline.

Lower incidence of reoperation with longer shunt survival with adult ventriculoperitoneal shunts placed for hemorrhage-related hydrocephalus.

OBJECTIVE: The incidence of reoperation for ventriculoperitoneal shunts (VPS) in adults, although lower than in pediatric patients, is not insignificant. We hypothesize that adult VPS placed for hemorrhage-related hydrocephalus have a lower incidence of reoperation than those placed for other types of hydrocephalus. METHODS: We retrospectively reviewed all adult (>/= 20 yr) VPS initially placed from February 2001 to August 2006 at the University of Florida. We determined the incidence and time interval to reoperation. Follow-up was conducted by telephone interview and review of medical records. RESULTS: A total of 286 adult VPS were initially placed: 96 (34%) hemorrhage and 190 (66%) nonhemorrhage. A total of 15 (16%) hemorrhage patients underwent 22 shunt reoperations, compared with 50 (27%) nonhemorrhage patients who underwent 82 shunt reoperations (P = 0.0316). A Poisson regression analysis of the number of reoperations, factoring hemorrhage, age, and sex, demonstrated a significantly lower incidence of reoperation in hemorrhage patients (P = 0.0900). A Cox proportional hazards model analysis of time to first reoperation, factoring hemorrhage, age, and sex, demonstrated a significantly longer shunt survival in hemorrhage patients (P = 0.0404). CONCLUSION: Adult VPS placed for hemorrhage-related hydrocephalus have a significantly lower incidence of reoperation and significantly longer shunt survival. This result may be related to an incidence of transient shunt dependency in patients with hemorrhage-related hydrocephalus. However, the precise mechanism remains unclear.

History of craniosynostosis surgery and the evolution of minimally invasive endoscopic techniques: the University of Florida experience.

Craniosynostosis is the premature and abnormal fusion of 1 of the 6 suture lines that form the living skull and can occur as part of a syndrome or as an isolated defect (nonsyndromic). The first reported surgical procedure for correction of craniosynostosis was performed in 1890 by Lannelongue who advocated releasing, but not resecting, the fused suture. Craniofacial surgery has developed its own identity in the last 3 decades, with the Frenchman Tessier seen as the founding father. There have been many new developments such as distraction osteogenesis, biodegradable miniplate fixation, and the development of minimally invasive endoscopic techniques. Through the pioneering work of Jimenez and Barone, minimally invasive approaches to the surgical correction of craniosynostosis are now gaining wider acceptance. Here the authors review the history of craniosynostosis, the current literature and technique for endoscopic repair of craniosynostosis, as well as their own experience at the University of Florida, with minimally invasive endoscope-assisted techniques.

Salvaging the "lost peritoneum" after ventriculoatrial shunt failures.

OBJECTIVE: Placement of a ventriculoperitoneal (VP) shunt is the long-standing treatment of choice for hydrocephalus. However, in many patients with repeated distal failures, ventriculoatrial (VA) shunts are placed. Should the VA shunt fail, finding appropriate distal sites is often difficult. MATERIALS AND METHODS: We identified six patients, over a 3-year period, in whom conversion of VA to VP shunt was successfully performed with the aid of diagnostic laparoscopy or laparotomy. There were no ensuing shunt failures during the follow-up period (mean 1.5 years). CONCLUSION: Because of the benefits of VP over VA shunting, every effort should be made to preserve the peritoneum as the target for the distal catheter. Laparotomy/laparoscopy is useful in locating suitable peritoneal targets when converting to VP shunt after VA shunt failure, or as a final effort before VA shunt conversion.

Congenital craniopharyngioma and hypercalcemia induced by parathyroid hormone-related protein.

OBJECTIVE: To report a case of congenital craniopharyngioma and parathyroid hormone-related protein (PTHrP)-associated humoral hypercalcemia. METHODS: Details of this unusual case are reviewed, from detection of fetal hydrocephalus and a brain tumor, through cesarean delivery at 36 weeks of gestation, to subsequent laboratory studies, management, and confirmation of the diagnosis. RESULTS: Although PTHrP has been well documented as a cause of humoral hypercalcemia of malignancy (HHM) in adult patients with cancer, HHM is uncommon in children. In addition, HHM has rarely been ascribed to nonmalignant tumors. To the best of our knowledge, we report the first case of a neonate with congenital craniopharyngioma and refractory hypercalcemia (peak ionized calcium level of 1.92 mmol/L; normal, 1.05 to 1.3) attributed to an elevated PTHrP value of 8.6 pmol/L (normal, less than 4.7). Intact parathyroid hormone was appropriately undetectable (less than 10 pg/mL; normal, 15 to 65). Despite calcitonin treatment, the hypercalcemia persisted. Although pamidronate infusion stabilized the serum calcium level, the baby did not survive. CONCLUSION: The diagnosis of craniopharyngioma was confirmed at autopsy, and immunohistochemical studies substantiated that the craniopharyngioma produced PTHrP.