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Dachling Pang, Joseph A. Horton, John M. Herron, James E. Wilberger Jr. and John K. Vries

✓ With the advent of computerized tomography (CT), an increasing number of patients with only minimal neurological symptoms and no signs of brain herniation are found to harbor subacute or chronic extradural hematomas (EH's). The authors present the cases of 11 symptomatic but neurologically normal children with medium to large EH's managed by close observation. These EH's were discovered 4 hours to 6 days after injury; three were in the posterior fossa, seven over the frontoparietal convexity, and one in the temporal fossa. These clots were followed by serial CT scans. Nine children recovered without surgery from 4 to 18 days after injury, and all had evidence on CT of spontaneous clot resorption. Of these nine EH's, five clots displayed volume expansion from 5 to 16 days after injury before final resorption occurred. Expansion correlated with persistence or increase in symptoms, whereas resorption correlated with improvement. Two patients showed gradual uncal herniation on Days 6 and 8, respectively, presumably during the “expansile phase” of their clots. Both had emergency craniotomy and recovered without morbidity. It is hypothesized that the resorption dynamics of the subacute or chronic EH are similar to that of the chronic subdural hematoma, with predictable volume changes, and the outcome of each lesion depends on the interplay between the patient's intracranial pressure buffering capacity and the rate of volume change. If subtle signs of brain dysfunction are adopted to signal the failure of conservative treatment and the need for craniotomy, these patients may be safely, and many successfully, managed without surgery. Factors that influence outcome of medical treatment include the size, location, configuration, and the rapidity of accumulation of the clot, the presence of associated intradural lesions, the extracranial decompression of blood through skull diastases, and the age of the patient. These factors, the criteria for patient selection, and the indications for immediate operative intervention are discussed.

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Dachling Pang, Herman H. Tse, Marike Zwienenberg-Lee, Matthew Smith and John Zovickian

Object. Hydroxyapatite cement (HAC) is used with increasing frequency by craniofacial surgeons for building facial and skull base structures and by neurosurgeons for cranioplasty. Failures of HAC in cranioplasty have been attributed to breakage due to subjacent cerebrospinal fluid (CSF) pulsations through the dura mater. The authors describe a technique that involves inserting a resorbable MacroPore perforated plate to dampen CSF pulsations and then pouring HAC over the plate to fill a cranial defect and complete skull contouring.

Methods. Fifteen children ranging in age from 2 to 9.5 years were included in the study; the size of the skull defects in these patients ranged from 6.25 to 42.5 cm2, with a mean of 20.65 cm2. Patients in whom the combined MacroPore—HAC devices were implanted underwent follow-up examinations that included serial skull radiography and computerized tomography scans. No fractures of the implants were demonstrated. At 6 months postsurgery, small fingerlings of new bone growth appeared in the underside of the HAC plate, probably spanning from the dura through perforations in the MacroPore plate. At intervals ranging from 18 months to 20 years after implantation, the gaps between cranial bone edges and that the HAC began to blur, culminating in the complete bonding of host bone with the margin of the HAC plate. All implants remained radiopaque and maintained size, thickness, and shape.

Conclusions. The findings of this study are promising and indicate that the combined use of HAC and a bioresorbable undercarriage that is osteoconductive, such as the MacroPore perforated plate, may produce a versatile and lasting cranioplasty in children.

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Dachling Pang, Marike Zwienenberg-Lee, Matthew Smith and John Zovickian

✓Cranial nerve palsy is rarely seen after shunt placement in an isolated fourth ventricle. In the few reports of this complication, neuropathies are thought to be caused by catheter injury to the brainstem nuclei either during the initial cannulations or after shrinkage of the fourth ventricle. The authors treated a child who suffered from delayed, progressive palsies of the sixth, seventh, 10th, and 12th cranial nerves several weeks after undergoing ventriculoperitoneal shunt placement in the fourth ventricle. Magnetic resonance imaging revealed the catheter tip to be placed well away from the ventricular floor but the brainstem had severely shifted backward, suggesting that the pathogenesis of the neuropathies was traction on the affected cranial nerves. The authors postulated that the siphoning effect of the shunt caused rapid collapse of the fourth ventricle and while the cerebellar hemispheres were tented back by adhesions to the dura, the brainstem became the only mobile component in response to the suction forces. Neurological recovery occurred after surgical opening of the closed fourth ventricle and lysis of the basal cistern adhesions, which restored moderate ventricular volume and released the brainstem to its normal position.

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Sui-To Wong, Kimberly Ernest, Grace Fan, John Zovickian and Dachling Pang

Only 6 cases of isolated unilateral rupture of the alar ligament have been previously reported. The authors report a new case and review the literature, morbid anatomy, and pathogenesis of this rare injury. The patient in their case, a 9-year-old girl, fell head first from a height of 5 feet off the ground. She presented with neck pain, a leftward head tilt, and severe limitation of right rotation, extension, and right lateral flexion of the neck. Plain radiographs and CT revealed no fracture but a shift of the dens toward the right lateral mass of C-1. Magnetic resonance imaging of the cervical spine showed signal hyperintensity within the left dens-atlas space on both T1- and T2-weighted sequences and interruption of the expected dark signal representing the left alar ligament, suggestive of its rupture. After 12 weeks of immobilization in a Guilford brace, MRI showed lessened dens deviation, and the patient attained full and painless neck motion.

Including the patient in this case, the 7 patients with this injury were between 5 and 21 years old, sustained the injury in traffic accidents or falls, presented with marked neck pain, and were treated with external immobilization. All patients had good clinical outcome. The mechanism of injury is hyperflexion with rotation. Isolated unilateral alar ligament rupture is a diagnosis made by excluding associated fracture, dislocation, or disruption of other major ligamentous structures in the craniovertebral junction. CT and MRI are essential in establishing the diagnosis. External immobilization is adequate treatment.

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Sui-To Wong, John Zovickian, Yongjin Hou, Chris Sonne and Dachling Pang

The authors report the first case of unilateral traumatic rupture of the C-2 neurocentral synchondrosis. A 26-month-old child was in a vehicular collision that caused his head to be rotated sharply to the left with the neck flexed. He had severe neck pain but was neurologically normal. Computerized tomography scanning showed rupture of the left C-2 neurocentral synchondrosis, a right C-2 pars interarticularis fracture, and anterior angulation of C-2 on C-3. The neck injury was unrecognized until postinjury Day 9 when an MRI study showed a tear of the posterior longitudinal ligament at C2–3 and separation of the C-2 body from the inferior anular epiphysis. A second CT showed widening of the synchondrosis fracture, increased angulation of C-2 on C-3, and distraction of the right C-2 pars fracture. The mechanism of the neurocentral synchondrosis fracture is thought to be hyperflexion-axial loading combined with leftward rotation, which provided the lateral force that overcame the cartilaginous synchondrosis and extruded the lateral mass. The patient underwent open reduction and posterior fusion of C1–3, and was maintained in a halo jacket for 4 months, when CT scans demonstrated solid C1–C3 fusion and ossification of the injured synchondrosis. Unilateral traumatic rupture of the C-2 neurocentral synchondrosis is one component of several injuries involving C-2 sustained before synchondrosis closure. The resulting C2–3 relationship is highly unstable. Reduction and C1–C3 fusion are necessary in patients with significant displacement of the adjacent bony units.

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Justin Seltzer, Charles E. Ashton, Thomas C. Scotton, Dhiraj Pangal, John D. Carmichael and Gabriel Zada

OBJECT

Functional corticotroph pituitary adenomas (PAs) secrete adrenocorticotropic hormone (ACTH) and are the cause of Cushing's disease, which accounts for 70% of all cases of Cushing's syndrome. Current classification systems for PAs rely primarily on laboratory hormone findings, tumor size and morphology, invasiveness, and immunohistochemical findings. Likewise, drug development for functional ACTH-secreting PAs (ACTH-PAs) is limited and has focused largely on blocking the production or downstream effects of excess cortisol. The authors aimed to summarize the findings from previous studies that explored gene and protein expression of ACTH-PAs to prioritize potential genetic and protein targets for improved molecular diagnosis and treatment of Cushing's disease.

METHODS

A systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PubMed search of select medical subject heading (MeSH) terms was performed to identify all studies that reported gene- and protein-expression findings in ACTH-PAs from January 1, 1990, to August 24, 2014, the day the search was performed. The inclusion criteria were studies on functional ACTH-PAs compared with normal pituitary glands, on human PA tissue only, with any method of analysis, and published in the English language. Studies using anything other than resected PA tissue, those that compared other adenoma types, those without baseline expression data, or those in which any pretreatment was delivered before analysis were excluded.

RESULTS

The primary search returned 1371 abstracts, of which 307 were found to be relevant. Of those, 178 were selected for secondary full-text analysis. Of these, 64 articles met the inclusion criteria and an additional 4 studies were identified from outside the search for a total of 68 included studies. Compared with the normal pituitary gland, significant gene overexpression in 43 genes and 22 proteins was reported, and gene underexpression in 58 genes and 15 proteins was reported. Immunohistochemistry was used in 39 of the studies, and reverse transcriptase polymerase chain reaction was used in 26 of the studies, primarily, and as validation for 4 others. Thirteen studies used both immunohistochemistry and reverse transcriptase polymerase chain reaction. Other methods used included microarray, in situ hybridization, Northern blot analysis, and Western blot analysis. Expression of prioritized genes emphasized in multiple studies were often validated on both the gene and protein levels. Genes/proteins found to be overexpressed in ACTH-PAs relative to the normal pituitary gland included hPTTG1/securin, NEUROD1/NeuroD1 (Beta2), HSD11B2/11β-hydroxysteroid dehydrogenase 2, AKT/Akt, protein kinase B, and CCND1/cyclin D1. Candidate genes/proteins found to be underexpressed in ACTH-PAs relative to the normal pituitary gland included CDKN1B/p27Kip1, CDKN2A/p16, KISS1/kisspeptin, ACTHR/ACTH-R, and miR-493.

CONCLUSIONS

On the basis of the authors' systematic review, many significant gene and protein targets that may contribute to tumorigenesis, invasion, and hormone production/secretion of ACTH have been identified and validated in ACTH-PAs. Many of these potential targets have not been fully analyzed for their therapeutic and diagnostic potential but may represent candidate molecular targets for biomarker development and drug targeting. This review may help catalyze additional research efforts using modern profiling and sequencing techniques and alteration of gene expression.

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Jennifer E. Kim, John Pang, Joani M. Christensen, Devin Coon, Patricia L. Zadnik, Jean-Paul Wolinsky, Ziya L. Gokaslan, Ali Bydon, Daniel M. Sciubba, Timothy Witham, Richard J. Redett and Justin M. Sacks

OBJECT

Total en bloc sacrectomy is a dramatic procedure that results in extensive sacral defects. The authors present a series of patients who underwent flap reconstruction after total sacrectomy, report clinical outcomes, and provide a treatment algorithm to guide surgical care of this unique patient population.

METHODS

After institutional review board approval, data were collected for all patients who underwent total sacrectomy between 2002 and 2012 at The Johns Hopkins Hospital. Variables included demographic data, medical history, tumor characteristics, surgical details, postoperative complications, and clinical outcomes. All subtotal sacrectomies were excluded.

RESULTS

Between 2002 and 2012, 9 patients underwent total sacrectomy with flap reconstruction. Diagnoses included chordoma (n = 5), osteoblastoma (n = 1), sarcoma (n = 2), and metastatic colon cancer (n = 1). Six patients received gluteus maximus (GM) flaps with a prosthetic rectal sling following a single-stage, posterior sacrectomy. Four required additional paraspinous muscle (PSM) or pedicled latissimus dorsi (LD) fasciocutaneous flaps. Three patients underwent multistage sacrectomy with an anterior-posterior approach, 2 of whom received pedicled vertical rectus abdominis myocutaneous (VRAM) flaps, and 1 of whom received local GM, LD, and PSM flaps. Flap complications included dehiscence (n = 4) and infection (n = 1). During the 1st year of follow-up, 2 of 9 patients (22%) were able to ambulate with an assistive device by the 1st postoperative month, and 6 of 9 (67%) were ambulatory with a walker by the 3rd postoperative month. By postoperative Month 12, 5 of 9 patients (56%)—or 5 of 5 patients not lost to follow-up (100%)—were able to able to ambulate independently.

CONCLUSIONS

The authors' experience suggests that the GM and pedicled VRAM flaps are reliable options for softtissue reconstruction of total sacrectomy defects. For posterior-only operations, GM flaps with or without a prosthetic rectal sling are generally used. For multistage operations including a laparotomy, the authors consider the pedicled VRAM flap to be the gold standard for simultaneous reconstruction of the pelvic diaphragm and obliteration of dead space.