Publications by authors named "Deb Bhowmick"

21 Publications

  • Page 1 of 1

Limitations on Postoperative Opioid Prescriptions and Effects on Health Care Resource Use Following Elective Anterior Cervical Discectomy and Fusion.

World Neurosurg 2021 02 27;146:e501-e508. Epub 2020 Oct 27.

Department of Neurosurgery, University of North Carolina School of Medicine, Durham, North Carolina, USA.

Objective: To curb the misuse of postoperative prescription opioids, the state of North Carolina enacted the Strengthen Opioid Misuse Prevention (STOP) Act of 2017 limiting the duration of initial postoperative opioid prescriptions. The purpose of this study was to evaluate the STOP Act's effect on health care resource use by comparing patient outcomes and opioid prescribing practices following elective anterior cervical discectomy and fusion (ACDF).

Methods: Outcomes and opioid prescribing data were retrospectively evaluated for Pre-Law (January 1, 2017, to December 31, 2017) and Post-Law (January 1, 2018, to December 31, 2018) elective 1- to 4-level anterior cervical discectomy and fusion patient cohorts. Outcome measures included hospital and clinic resource use in the form of emergency department visits, readmissions, major postoperative complications, number of clinic visits, or number of clinic phone calls by patients reporting uncontrolled pain or requesting new opioid prescriptions. Opioid-prescribing practices in the form of discharge prescription number of pills and total morphine milliequivalents also were recorded.

Results: Surrounding the STOP Act's implementation, there was no significant difference (P > 0.05) in emergency department visits, readmissions, major complications, number of postoperative clinic visits, or number of clinic phone calls for uncontrolled pain or new prescription requests. There was a significant decline in mean discharge prescription number of pills (89.7 vs. 67.0, P < 0.001), and average morphine milliequivalents (683.4 vs. 509.6, P < 0.001).

Conclusions: This may reflect overprescribing in this population, where larger opioid prescriptions were likely not needed to manage pain that would otherwise require a return to care.
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http://dx.doi.org/10.1016/j.wneu.2020.10.119DOI Listing
February 2021

Gender Disparities in Surgical Treatment of Axis Fractures in Older Adults.

Global Spine J 2021 Jan 25;11(1):71-75. Epub 2019 Nov 25.

2331University of North Carolina, Chapel Hill, NC, USA.

Study Design: Retrospective cohort study.

Objectives: Gender appears to play in important role in surgical outcomes following acute cervical spine trauma, with current literature suggesting males have a significantly higher mortality following spine surgery. However, no well-adjusted population-based studies of gender disparities in incidence and outcomes of spine surgery following acute traumatic axis injuries exist to our knowledge. We hypothesized that females would receive surgery less often than males, but males would have a higher 1-year mortality following isolated traumatic axis fractures.

Methods: We performed a retrospective cohort study using Medicare claims data that identified US citizens aged 65 and older with ICD-9 (International Classification of Diseases, Ninth Revision) code diagnosis corresponding to isolated acute traumatic axis fracture between 2007 and 2014. Our primary outcome was defined as cumulative incidence of surgical treatment, and our secondary outcome was 1-year mortality. Propensity weighted analysis was performed to balance covariates between genders. Our institutional review board approved the study (IRB #16-0533).

Results: There was no difference in incidence of surgery between males and females following acute isolated traumatic axis fractures (7.4 and 7.5 per 100 fractures, respectively). Males had significantly higher 1-year weighted mortality overall (41.7 and 28.9 per 100 fractures, respectively, < .001).

Conclusion: Our well-adjusted data suggest there was no significant gender disparity in incidence of surgical treatment over the study period. The data also support previous observations that males have worse outcomes in comparison to females in the setting of axis fractures and spinal trauma regardless of surgical intervention.
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http://dx.doi.org/10.1177/2192568219890573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734274PMC
January 2021

1-Year Mortality and Surgery Incidence in Older US Adults with Cervical Spine Fracture.

World Neurosurg 2020 09 12;141:e858-e863. Epub 2020 Jun 12.

Department of Neurosurgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: Traumatic cervical spinal cord injuries (SCIs) can be lethal and are especially dangerous for older adults. Falls from standing and risk factors for a cervical fracture and spinal cord injury increase with age. This study estimates the 1-year mortality for patients with a cervical fracture and resultant SCI and compares the mortality rate with that from an isolated cervical fracture.

Methods: We performed a retrospective cohort study of U.S. Medicare patients older than 65 years of age. International Classification of Diseases (ICD)-9 codes were used to identify patients with a cervical fracture without SCI and patients with a cervical fracture with SCI between 2007 and 2014. Our primary outcome was 1-year mortality cumulative incidence rate; our secondary outcome was the cumulative incidence rate of surgical intervention. Propensity weighted analysis was performed to balance covariates between the groups.

Results: The SCI cohort had a 1-year mortality of 36.5%, compared with 31.1% in patients with an isolated cervical fracture (risk difference 5.4% (2.9%-7.9%)). Patients with an SCI were also more likely to undergo surgical intervention compared with those without a SCI (23.1% and 10.3%, respectively; risk difference 12.8% (10.8%-14.9%)).

Conclusions: Using well-adjusted population-level data in older adults, this study estimates the 1-year mortality after SCI in older adults to be 36.5%. The mortality after a cervical fracture with SCI was 5 percentage points higher than in patients without SCI, and this difference is smaller than one might expect, likely representing the frailty of this population and unmeasured covariates.
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http://dx.doi.org/10.1016/j.wneu.2020.06.070DOI Listing
September 2020

Comparative Propensity-Weighted Mortality After Isolated Acute Traumatic Axis Fractures in Older Adults.

Geriatr Orthop Surg Rehabil 2020 30;11:2151459320911867. Epub 2020 Mar 30.

Department of Neurosurgery, UNC School of Medicine, NC, USA.

Introduction: In older patients with axis fractures, the survival benefit from surgery is unclear due to high baseline mortality. Comparative effectiveness research can provide evidence from population level cohorts. Propensity weighting is the preferred methodology for reducing bias when analyzing national administrative cohort data for these purposes but has not yet been utilized for this important surgical conundrum. We estimate the effect of surgery on mortality after isolated acute traumatic axis fracture in older adults.

Materials And Methods: We used a retrospective population-based cohort of Medicare patients and generated a propensity score-weighted nonsurgical cohort and compared mortality with and without surgery. This balanced the comorbid conditions of the treatment groups. Incident fractures were defined using a predetermined algorithm based on enrollment, code timing, and billing location. The primary outcome was adjusted all-cause 1-year mortality.

Results: From 12 372 beneficiaries with 1-year continuous enrollment and a coded axis fracture, 2676 patients met final inclusion/exclusion criteria. Estimated incidence was 16.5 per 100 000 person-years overall in 2014 (95% confidence interval [CI]: 15.0-18.0) and was stable from 2008 through 2014. Patients with axis fracture had a mean age of 82.8 years, 30.2% were male, and 91.9% were Caucasian. Mortality was 3.8 times higher (CI 3.6-4.1) compared with the general population of older US adults. Propensity-weighted mortality at 1 year for nonsurgical patients was 26.7 of 100 (CI: 24.5-29.0). Mortality for surgical patients was significantly lower (19.7/100; CI 14.5-25.0). Risk difference was 7.0 fewer surgical deaths per 100 patients (CI: 1.3-12.7). Surgical patients aged 65 to 74 years had the largest difference in mortality with 11.2 fewer deaths per 100 (CI: 1.1-21.3).

Discussion: Patients with axis fractures are predominantly older Caucasian women and have a higher mortality rate than the general population. Propensity-weighted mortality at 1-year was lower in the surgical patients with the largest risk difference occurring in patients 65 to 74 years old.

Conclusions: Surgery may provide an independent survival benefit in patients aged 65 to 75 years, and the mortality difference diminishes thereafter.
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http://dx.doi.org/10.1177/2151459320911867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133078PMC
March 2020

Use of C2 vertebroplasty and stereotactic radiosurgery for treatment of lytic metastasis of the odontoid process.

J Craniovertebr Junction Spine 2017 Jul-Sep;8(3):285-287

Department of Neurosurgery, University of North Carolina, NC 27599, USA.

Improvements in cancer therapy have led to increased patient survival times in spite of metastatic spinal disease in many forms of cancer. Conventional treatment methods often employ radiotherapy with or without surgery depending on the neurological status, mechanical instability, and the extent of tumor. Percutaneous vertebroplasty as well as stereotactic radiosurgery (SRS) have arisen as common modalities of treatment of spinal metastasis in which neurological compromise or spinal instability and deformity is not of significant concern. These treatments, when used in combination, have been shown to provide early pain relief and effective tumor control while avoiding surgical resection, fixation, and lengthy recovery times. We present a case unique in the literature for the use of this combination treatment for tumors of the C2 vertebral body. While limited in application to patients without overt atlantoaxial instability or significant spinal canal compromise, we believe it provides a significant benefit in decreasing morbidity and improving early adherence to systemic therapy.
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http://dx.doi.org/10.4103/jcvjs.JCVJS_63_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634119PMC
October 2017

Variant prostate carcinoma and elevated serum CA-125.

Can J Urol 2014 Oct;21(5):7442-8

The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Introduction: About 10% of tumors derived from nongynecologic, noncoelomic tissues react with the OC125 antibody. Some patients with advanced prostate cancer were found to have elevated serum CA-125 level.

Materials And Methods: We examined the clinical history of 11 patients with castration resistant prostate cancer and an elevated serum CA-125 level. Pathological review and immunohistochemical staining were performed on tumors from eight of these patients.

Results: Patients with advanced prostate cancer and an elevated serum CA-125 level responded to androgen ablative therapy (median duration, 27 months). They were predisposed to develop persistent or recurrent urinary symptoms and visceral metastases. Eight of 11 patients had a low or undetectable serum prostate-specific antigen level (≤ 4 ng/mL) or an elevated serum carcinoembryonic antigen level (> 6 ng/mL). In 3 of 7 patients whose specimens were available for further review, the tumors contained histologic features compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate.

Conclusions: Patients with prostate cancer and an elevated serum CA-125 level have unique clinical and pathologic characteristics. Some of these patients possess tumors compatible with a subtype of prostate cancer known as ductal adenocarcinoma. Additional studies need to be performed to elucidate the biologic basis of the various subtypes of prostate cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400850PMC
October 2014

Biomechanical analysis of the upper thoracic spine after decompressive procedures.

Spine J 2014 Jun 1;14(6):1010-6. Epub 2013 Dec 1.

Department of Neurosurgery, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, S4, Cleveland, OH 44195, USA.

Background Context: Decompressive procedures such as laminectomy, facetectomy, and costotransversectomy are routinely performed for various pathologies in the thoracic spine. The thoracic spine is unique, in part, because of the sternocostovertebral articulations that provide additional strength to the region relative to the cervical and lumbar spines. During decompressive surgeries, stability is compromised at a presently unknown point.

Purpose: To evaluate thoracic spinal stability after common surgical decompressive procedures in thoracic spines with intact sternocostovertebral articulations.

Study Design: Biomechanical cadaveric study.

Methods: Fresh-frozen human cadaveric spine specimens with intact rib cages, C7-L1 (n=9), were used. An industrial robot tested all spines in axial rotation (AR), lateral bending (LB), and flexion-extension (FE) by applying pure moments (±5 Nm). The specimens were first tested in their intact state and then tested after each of the following sequential surgical decompressive procedures at T4-T5 consisting of laminectomy; unilateral facetectomy; unilateral costotransversectomy, and subsequently instrumented fusion from T3-T7.

Results: We found that in all three planes of motion, the sequential decompressive procedures caused no statistically significant change in motion between T3-T7 or T1-T12 when compared with intact. In comparing between intact and instrumented specimens, our study found that instrumentation reduced global range of motion (ROM) between T1-T12 by 16.3% (p=.001), 12% (p=.002), and 18.4% (p=.0004) for AR, FE, and LB, respectively. Age showed a negative correlation with motion in FE (r = -0.78, p=.01) and AR (r=-0.7, p=.04).

Conclusions: Thoracic spine stability was not significantly affected by sequential decompressive procedures in thoracic segments at the level of the true ribs in all three planes of motion in intact thoracic specimens. Age appeared to negatively correlate with ROM of the specimen. Our study suggests that thoracic spinal stability is maintained immediately after unilateral decompression at the level of the true ribs. These preliminary observations, however, do not depict the long-term sequelae of such procedures and warrant further investigation.
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http://dx.doi.org/10.1016/j.spinee.2013.11.035DOI Listing
June 2014

Minimally invasive, robot-assisted, anterior lumbar interbody fusion: a technical note.

J Neurol Surg A Cent Eur Neurosurg 2013 Jul 11;74(4):258-61. Epub 2013 Jan 11.

Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Background: Minimally invasive techniques in spine surgery have gained significant popularity due to decreased tissue dissection and destruction, postoperative pain, and hospital stay. The laparoscopic anterior lumbar interbody fusion (ALIF), an innovation in minimally invasive spine surgery, is rarely done because it has marginal benefit over the mini-open ALIF technique in rates of retrograde ejaculation and vascular complications. We propose these outcomes can be improved with enhanced robotic-assisted dissection and exposure for ALIF.

Patients: Two patients with single-level degenerative spine disease at L5-S1, associated with mechanical back pain, underwent anterior spinal exposure using the da Vinci S Surgical Robot during ALIF.

Results: In this report, we provide the first description of the use of a surgical robot in the dissection and exposure for ALIF in patients with degenerative spine disease. We demonstrate successful use of the da Vinci Surgical Robot in separating the presacral nervous plexus from retroperitoneal structures without postoperative vascular or urological complications over a 1-year follow-up period.

Conclusion: Use of the robotic assistance in the performance of ALIF is possible without significant operative complications. This technique may provide added benefit over conventional laparoscopic approaches to the spine.
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http://dx.doi.org/10.1055/s-0032-1330121DOI Listing
July 2013

Posterior atlantoaxial fixation with screw-rod constructs: safety, advantages, and shortcomings.

World Neurosurg 2014 Feb 24;81(2):288-9. Epub 2012 Oct 24.

Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, and Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. Electronic address:

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http://dx.doi.org/10.1016/j.wneu.2012.10.024DOI Listing
February 2014

Cervical orthoses after atlantoaxial fixation: who are we treating, the patient or ourselves?

World Neurosurg 2013 Feb 24;79(2):271-2. Epub 2012 Oct 24.

Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio, USA.

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http://dx.doi.org/10.1016/j.wneu.2012.10.030DOI Listing
February 2013

Functionalization of amorphous SiO₂ and 6H-SiC(0001) surfaces with benzo[ghi]perylene-1,2-dicarboxylic anhydride via an APTES linker.

Small 2012 Feb 19;8(4):592-601, 619. Epub 2012 Jan 19.

Physikalisches Institut and Center for Nanotechnology (CeNTech), Wilhelm-Klemm-Str. 10, University of Münster, 48149 Münster, Germany.

The successful covalent functionalization of quartz and n-type 6H-SiC with organosilanes and benzo[ghi]perylene-1,2-dicarboxylic dye is demonstrated. In particular, wet-chemically processed self-assembled layers of aminopropyltriethoxysilane (APTES) and benzo[ghi]perylene-1,2-dicarboxylic anhydride are investigated. The structural and chemical properties of these layers are studied by contact angle measurements, attenuated total reflection infrared (ATR-IR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). The optical properties are measured by confocal microscopy. The wetting angles observed for the organic layers are α = 68° for the APTES-functionalized surface, while angles of α = 85° and 78° are determined for dye-functionalized quartz and 6H-SiC surfaces, respectively. However, not all amino groups of the APTES-functionalized surfaces react to bind dye molecules. Further dye functionalization is not uniform throughout the surface, showing different island sizes of the dye and including different chemical environments. The quartz surface exhibits a higher packing density of dyes than the 6H-SiC surface. The fluorescence lifetimes of the surface-attached dye show double exponential decays of about 1.4 and 4.2 ns, largely independent of the substrates.
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http://dx.doi.org/10.1002/smll.201101941DOI Listing
February 2012

Salvage C2 ganglionectomy after C2 nerve root decompression provides similar pain relief as a single surgical procedure for intractable occipital neuralgia.

World Neurosurg 2012 Feb 7;77(2):362-9. Epub 2011 Nov 7.

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objective: To determine the effectiveness of C2 nerve root decompression and C2 dorsal root ganglionectomy for intractable occipital neuralgia (ON) and C2 ganglionectomy after pain recurrence following initial decompression.

Methods: A retrospective review was performed of the medical records of patients undergoing surgery for ON. Pain relief at the time of the most recent follow-up was rated as excellent (headache relieved), good (headache improved), or poor (headache unchanged or worse). Telephone contact supplemented chart review, and patients rated their preoperative and postoperative pain on a 10-point numeric scale. Patient satisfaction and disability were also examined.

Results: Of 43 patients, 29 were available for follow-up after C2 nerve root decompression (n = 11), C2 dorsal root ganglionectomy (n = 10), or decompression followed by ganglionectomy (n = 8). Overall, 19 of 29 patients (66%) experienced a good or excellent outcome at most recent follow-up. Among the 19 patients who completed the telephone questionnaire (mean follow-up 5.6 years), patients undergoing decompression, ganglionectomy, or decompression followed by ganglionectomy experienced similar outcomes, with mean pain reduction ratings of 5 ± 4.0, 4.5 ± 4.1, and 5.7 ± 3.5. Of 19 telephone responders, 13 (68%) rated overall operative results as very good or satisfactory.

Conclusions: In the third largest series of surgical intervention for ON, most patients experienced favorable postoperative pain relief. For patients with pain recurrence after C2 decompression, salvage C2 ganglionectomy is a viable surgical option and should be offered with the potential for complete pain relief and improved quality of life (QOL).
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http://dx.doi.org/10.1016/j.wneu.2011.06.062DOI Listing
February 2012

Da Vinci Robot-assisted transoral odontoidectomy for basilar invagination.

ORL J Otorhinolaryngol Relat Spec 2010 1;72(2):91-5. Epub 2010 May 1.

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pa. 19104, USA.

The transoral approach is an effective way to decompress the craniocervical junction due to basilar invagination. This approach has been described and refined, but significant limitations and technical challenges remain. Specifically, should the transoral route be used for intradural pathology, such as a meningioma, or should an inadvertent durotomy occur during extradural dissection, achieving a watertight closure of the dura in such a deep and narrow working channel is limited with the current microscopic and endoscopic techniques. Even closure of the posterior pharyngeal mucosa can be challenging, and problems with wound dehiscence encountered in some case series may be attributable to this difficulty. These problems, and the corollary aversion to the procedure felt by many neurosurgeons, led our group to investigate an alternative approach.
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http://dx.doi.org/10.1159/000278256DOI Listing
September 2010

Treatment of pediatric atlantoaxial instability with traditional and modified Goel-Harms fusion constructs.

Eur Spine J 2009 Jun 9;18(6):884-92. Epub 2009 Apr 9.

Division of Neurosurgery, Department of Neurosurgery, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Wood Center, 6th Floor, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.

There are several treatment options for rigid fixation at C1-C2 including Brooks and Gallie type wired fusions and C1-2 transarticular screws. The use of a Goel-Harms type fusion, a construct with C1 lateral mass screws and C2 pedicle screws, has not been extensively described in pediatric patients. Here, we describe its relatively safe and effective use for treating pediatric patients by retrospective chart review of patients treated by the senior author for atlantoaxial instability with a Goel-Harms-type constructs during a 3-year period (2005-2007). Six patients were treated using Goel-Harms-type constructs. Five patients were treated utilizing a construct containing C1 lateral mass screws and C2 pedicle screws; one patient was treated using construct containing C1 lateral mass screws and C2 trans-laminar screws. The patients ranged in age from 7 to 17 years old (mean 12.7). All patients had findings of an os odontoideum on CT scans and three of the six patients had T2 hyperintensity on MRI. Three of the six patients presented with transient neurologic deficits: quadraplegia in two patients and paresthesias in two patients. In each patient C1 lateral mass and C2 screws were placed and the subluxation was reduced to attain an anatomical alignment. No bone grafts were harvested from the iliac crest or rib. Local morsalized bone and sub-occipital skull graft was used. All patients tolerated the procedure well and were discharged home on post-operative day 3-4. The patients wore a hard cervical collar and no halo-vests were needed. All patients had solid fusion constructs and normal alignment on post-operative imaging studies performed on average 14 months post-operatively (range: 7-29). The results demonstrated that Goel-Harms fusions are a relatively safe and effective method of treating pediatric patients with atlantoaxial instability and are not dependent on vertebral anatomy or an intact ring of C1. Follow-up visits and studies in this limited series of patients demonstrated solid fusion constructs and anatomical alignment in all patients treated.
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http://dx.doi.org/10.1007/s00586-009-0969-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2899651PMC
June 2009

Symptomatic high-flow arteriovenous fistula after a C-2 fracture. Case report.

J Neurosurg Spine 2008 Apr;8(4):381-4

Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Spinal arteriovenous fistulas (AVFs) are relatively uncommon lesions that are often diagnosed in a delayed fashion. The authors present a cause of a symptomatic high-flow AVF that developed in a patient after traumatic injury to the upper cervical spine. The patient presented to the trauma bay after a motor vehicle collision, and was found to have a C-2 fracture involving the transverse foramen. Although the patient was neurologically intact on presentation, 6 hours after admission weakness developed on his left side. Imaging studies demonstrated complete transection of the distal cervical aspect of the right vertebral artery (VA) at the base of C-2, with antegrade and retrograde flow into a direct AVF, resulting in early filling of the right internal jugular vein and other external draining veins. The patient was treated endovascularly with coil occlusion of the VA both proximal and distal to the transection. The patient's weakness improved over the next 7 days. At the 12-week follow-up examination, the patient's fractures had healed and he was neurologically intact.
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http://dx.doi.org/10.3171/SPI/2008/8/4/381DOI Listing
April 2008

Congenital cystic hemangioblastomas of the cerebral hemisphere in a neonate without alteration in the VHL gene.

Pediatr Neurosurg 2004 May-Jun;40(3):124-7

Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tenn., USA.

A 4-week-old child presented with lethargy, emesis, decreased spontaneous movements, and a bulging fontanelle. Neuroimaging demonstrated a large, hemispheric, multicystic lesion with multiple enhancing nodules, which, on pathological examination, proved to be multiple, distinct hemangioblastomas. Careful molecular analysis failed to reveal alterations of the VHL gene. This represents an uncommon presentation for these tumors and suggests that genes other than VHL may be important in the genesis of these tumors.
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http://dx.doi.org/10.1159/000079854DOI Listing
December 2004

Protein patterns and proteins that identify subtypes of glioblastoma multiforme.

Oncogene 2004 Sep;23(40):6806-14

Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892-1414, USA.

Glioblastoma multiforme (GBM) has been subdivided into two types based on clinical and genetic findings: primary tumors, which arise de novo, and secondary tumors, which progress from lower grade gliomas to GBMs. To analyse this dichotomy at the protein level, we employed selective tissue microdissection to obtain pure populations of tumor cells, which we studied using two-dimensional protein gel electrophoresis (2-DGE) and protein sequencing of select target proteins. Protein patterns were analysed in a blinded manner from the clinical and genetic data. 2-DGE clearly identified two distinct populations of tumors. 2-DGE was reproducible and reliable, as multiple samples analysed from the same patient gave identical results. In addition, we isolated and sequenced 11 proteins that were uniquely expressed in either the primary or the secondary GBMs, but not both. We demonstrate that specific proteomic patterns can be reproducibly identified by two-dimensional gel electrophoresis from limited numbers of selectively procured, microdissected tumor cells and that two patterns of GBMs, primary versus secondary, previously distinguished by clinical and genetic differences, can be recognized at the protein level. Proteins that are expressed distinctively may have important implications for the diagnosis, prognosis, and treatment of patients with GBM.
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http://dx.doi.org/10.1038/sj.onc.1207770DOI Listing
September 2004

A functional polymorphism in the EGF gene is found with increased frequency in glioblastoma multiforme patients and is associated with more aggressive disease.

Cancer Res 2004 Feb;64(4):1220-3

Surgical Neurology Branch, National Institutes of Neurological Disorders and Stroke/NIH, Building 10, Rm. 5D37, 9000 Rockville Pike, Bethesda, MD 20892-1414, USA.

Glioblastoma multiforme, the most aggressive form of primary brain tumor in adults, is nearly universally fatal, with 5-year survivals of <5% (P. Kleihues and W. K. Cavenee, eds., pp. 1-314, Lyon: IARC, 2000). Alterations in the epidermal growth factor receptor (EGFR) are common events in many glioblastoma. We hypothesized that a polymorphism in the 5'-untranslated region of the epidermal growth factor (EGF) gene, a natural ligand of the EGFR, may play a role in the genesis of these malignant gliomas. We find that patients with the GA or GG genotype have higher tumoral levels of EGF, irrespective of EGFR status, that they are more likely to recur after surgery, and that they have a statistically significant shorter overall progression-free survival than patients with the AA genotype. These findings suggest that a single nucleotide polymorphism in EGF may play a role in the formation of glioblastomas, is a useful and powerful prognostic marker for these patients, and may be a target for tumor therapy.
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http://dx.doi.org/10.1158/0008-5472.can-03-3137DOI Listing
February 2004

Somatic mutations in VHL germline deletion kindred correlate with mild phenotype.

Ann Neurol 2004 Feb;55(2):236-40

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20982, USA.

Generally, von Hippel-Lindau (VHL) disease is caused by a germline mutation of the VHL gene (chromosome 3p), and tumorigenesis is initiated from a "second-hit" deletion. A subset of VHL patients have a germline deletion of the VHL gene, and the molecular events leading to tumorigenesis are not fully understood. To determine the molecular pathogenesis of tumor formation in this setting, we analyzed five central nervous system hemangioblastomas from three patients of a single VHL germline deletion kindred, all displaying mild clinical phenotype. Rather than loss of heterozygosity (the "second hit" in VHL germline mutation patients), all tumors from this kindred showed "second-hit" point mutations on the wild-type allele. Moreover, in two patients who each had two hemangioblastomas resected each tumor contained a unique mutation. The specific germline deletion and the overall genetic makeup of the patient did not predict these random "second-hit" point mutations. These results suggest that in patients with germline deletion of a tumor suppressor gene there is a unique genetic mechanism underlying tumorigenesis. This unique genetic mechanism correlates with and may help to understand the mild clinical phenotype seen in these patients.
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http://dx.doi.org/10.1002/ana.10807DOI Listing
February 2004

Developmental arrest of angioblastic lineage initiates tumorigenesis in von Hippel-Lindau disease.

Cancer Res 2003 Nov;63(21):7051-5

Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke/NIH, 10 Center Drive, Bethesda, MD 20892, USA.

The nature of the cell responsible for von Hippel-Lindau (VHL) disease-associated tumor formation has been controversial for decades. We demonstrate that VHL disease-associated central nervous system tumors are composed of developmentally arrested angioblasts that coexpress erythropoietin (Epo) and Epo receptor. The angioblasts are capable of differentiating into RBCs via formation of blood islands with extramedullary hematopoiesis. Because of VHL deficiency, Epo receptor-expressing, developmentally arrested angioblasts simultaneously coexpress Epo, which may represent a crucial pathogenetic step in tumor formation.
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November 2003

Prostate carcinoma with testicular or penile metastases. Clinical, pathologic, and immunohistochemical features.

Cancer 2002 May;94(10):2610-7

Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.

Background: Despite the proximity, prostate carcinoma seldom metastasizes to the penis or testis.

Methods: In the current study, the authors retrospectively examined the clinical history of 12 patients with prostate carcinoma and testicular or penile metastases. Pathologic review and immunohistochemical staining were performed on tumors from eight of these patients.

Results: Patients with prostate carcinoma and testicular or penile metastasis responded to androgen ablative therapy (median duration, 33 months). They were predisposed to developing persistent or recurrent urinary symptoms and visceral metastases. Six of 9 evaluable patients had elevated serum carcinoembryonic antigen levels (> 6 ng/mL), whereas 2 of 10 patients had low or undetectable serum prostate specific antigen levels (< 4 ng/mL). In seven of the eight patients for whom specimens were available, the tumors were found to contain histologic features that were compatible with a diagnosis of ductal or endometrioid adenocarcinoma of the prostate.

Conclusions: Patients with prostate carcinoma and testicular or penile metastases have unique clinical and pathologic characteristics. Many of these patients' tumors are compatible with a subtype of prostate carcinoma known as ductal adenocarcinoma. Further studies need to be performed to elucidate the biologic basis of the various histologic subtypes of prostate carcinoma.
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http://dx.doi.org/10.1002/cncr.10546DOI Listing
May 2002
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