蝶手术后,库兴氏病(CD) shows excellent long-term remission rates, but it may recur and pose a therapeutic challenge. Findings in recent published reports on the treatment of recurrent adrenocorticotropic hormone (ACTH)–secreting tumors suggest that repeat resection, radiation-based therapies such as Gamma Knife surgery and proton-beam radiosurgery, pharmacotherapy, and bilateral adrenalectomy all have important roles in the treatment of recurrent CD. Each of these interventions has inherent risks and benefits that should be presented to the patient during counseling on retreatment options. Radiation-based therapies increasingly appear to have efficacies similar to those of repeat resection in achieving biochemical remission and tumor control. In addition, an expanding retinue of medication-based therapies, several of which are currently being evaluated in clinical trials, has shown some promise as tertiary adjunctive therapies. Lastly, bilateral adrenalectomy may offer durable control of refractory recurrent CD. An increasing number of published studies with long-term patient outcomes highlight the evolving treatment patterns in the management of recurrent CD.
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Martin J. Rutkowski, Patrick M. Flanigan, and Manish K. Aghi
Patrick Flanigan, Varun R. Kshettry, and Edward C. Benzel
丰富他的头颅成形术是一个独特的过程tory. Since ancient times, a diverse array of materials from coconut shells to gold plates has been used for the repair of cranial defects. More recently, World War II greatly increased the demand for cranioplasty procedures and renewed interest in the search for a suitable synthetic material for cranioprostheses. Experimental evidence revealed that tantalum was biologically inert to acid and oxidative stresses. In fact, the observation that tantalum did not absorb acid resulted in the metal being named after Tantalus, the Greek mythological figure who was condemned to a pool of water in the Underworld that would recede when he tried to take a drink. In clinical use, malleability facilitated a single-stage cosmetic repair of cranial defects. Tantalum became the preferred cranioplasty material for more than 1000 procedures performed during World War II. In fact, its use was rapidly adopted in the civilian population. During World War II and the heyday of tantalum cranioplasty, there was a rapid evolution in prosthesis implantation and fixation techniques significantly shaping how cranioplasties are performed today. Several years after the war, acrylic emerged as the cranioplasty material of choice. It had several clear advantages over its metallic counterparts. Titanium, which was less radiopaque and had a more optimal thermal conductivity profile (less thermally conductive), eventually supplanted tantalum as the most common metallic cranioplasty material. While tantalum cranioplasty was popular for only a decade, it represented a significant breakthrough in synthetic cranioplasty. The experiences of wartime neurosurgeons with tantalum cranioplasty played a pivotal role in the evolution of modern cranioplasty techniques and ultimately led to a heightened understanding of the necessary attributes of an ideal synthetic cranioplasty material. Indeed, the history of tantalum cranioplasty serves as a model for innovative thinking and adaptive technology development.
Jonathan Rick, Arman Jahangiri, Patrick M. Flanigan, Ankush Chandra, Sandeep Kunwar, Lewis Blevins, and Manish K. Aghi
OBJECTIVE
Acromegaly results in disfiguring growth and numerous medical complications. This disease is typically caused by growth hormone (GH)–secreting pituitary adenomas, which are treated first by resection, followed by radiation and/or medical therapy if needed. A subset of acromegalics have dual-staining pituitary adenomas (DSPAs), which stain for GH and prolactin. Presentations and treatment outcomes for acromegalics with DSPAs are not well understood.
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作者回顾了the records of more than 5 years of pituitary adenomas resected at their institution. Data were collected on variables related to clinical presentation, tumor pathology, radiological size, and disease recurrence. The Fisher’s exact test, ANOVA, Student t-test, chi-square test, and Cox proportional hazards and multiple logistic regression were used to measure statistical significance.
RESULTS
91年593例垂体腺瘤患者ed with acromegaly. Of these 91 patients, 69 (76%) had tumors that stained for GH only (single-staining somatotrophic adenomas [SSAs]), while 22 (24%) had tumors that stained for GH and prolactin (DSPAs). Patients with DSPAs were more likely to present with decreased libido (p = 0.012), signs of acromegalic growth (p = 0.0001), hyperhidrosis (p = 0.0001), and headaches (p = 0.043) than patients with SSAs. DSPAs presented with significantly higher serum prolactin (60.7 vs 10.0 µg/L, p = 0.0002) and insulin-like growth factor-1 (IGF-1) (803.6 vs 480.0 ng/ml, p = 0.0001), and were more likely to have IGF-1 levels > 650 ng/ml (n = 13 [81.3%] vs n = 6 [21.4%], p = 0.0001) than patients with SSAs despite similar sizes (1.8 vs 1.7 cm, p = 0.5). Patients with DSPAs under 35 years of age were more likely to have a recurrence (n = 4 [50.0%] vs n = 3 [11.1%], p = 0.01) than patients with SSAs under the age of 35. DSPA patients were less likely to achieve remission with surgery than SSA patients (n = 2 [20%] vs n = 19 [68%], p = 0.01). Univariate analysis identified single-staining tumors (p = 0.02), gross-total resection (p = 0.02), and tumor diameter (p = 0.05) as predictors of surgical remission. Multiple logistic regression demonstrated that SSAs (p = 0.04) were independently associated with surgical remission of acromegaly. Kaplan-Meier analysis revealed that DSPAs had more time until disease remission (p = 0.033).
CONCLUSIONS
Acromegalics with tumors that stain for prolactin and GH, which represented almost a quarter of acromegalics in this cohort, had more aggressive clinical presentations and postoperative outcomes than SSAs. Prolactin staining provides useful information for acromegalics undergoing pituitary surgery.
Arman Jahangiri, Aaron T. Chin, Patrick M. Flanigan, Rebecca Chen, Krystof Bankiewicz, and Manish K. Aghi
Glioblastoma is the most common malignant brain tumor, and it carries an extremely poor prognosis. Attempts to develop targeted therapies have been hindered because the blood-brain barrier prevents many drugs from reaching tumors cells. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. A number of alternative methods of delivery have been developed, one of which is convection-enhanced delivery (CED), the focus of this review. The authors describe CED as a therapeutic measure and review preclinical studies and the most prominent clinical trials of CED in the treatment of glioblastoma. The utilization of this technique for the delivery of a variety of agents is covered, and its shortcomings and challenges are discussed in detail.
Patrick M. Flanigan, Arman Jahangiri, Joshua L. Golubovsky, Jaret M. Karnuta, Francis J. May, Mitchel S. Berger, and Manish K. Aghi
OBJECTIVE
The position of neurosurgery department chair undergoes constant evolution as the health care landscape changes. The authors’ aim in this paper was to characterize career attributes of neurosurgery department chairs in order to define temporal trends in qualities being sought in neurosurgical leaders. Specifically, they investigated the hypothesis that increased qualifications in the form of additional advanced degrees and research acumen are becoming more common in recently hired chairs, possibly related to the increased complexity of their role.
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The authors performed a retrospective study in which they collected data on 105 neurosurgeons who were neurosurgery department chairs as of December 31, 2016, at accredited academic institutions with a neurosurgery residency program in the United States. Descriptive data on the career of neurosurgery chairs, such as the residency program attended, primary subspecialty focus, and age at which they accepted their position as chair, were collected.
RESULTS
The median age and number of years in practice postresidency of neurosurgery chairs on acceptance of the position were 47 years (range 36–63 years) and 14 years (range 6–33 years), respectively, and 87% (n = 91) were first-time chairs. The median duration that chairs had been holding their positions as of December 31, 2016, was 10 years (range 1–34 years). The most common subspecialties were vascular (35%) and tumor/skull base (27%), although the tendency to hire from these specialties diminished over time (p = 0.02). More recently hired chairs were more likely to be older (p = 0.02), have more publications (p = 0.007), and have higher h-indices (p < 0.001) at the time of hire. Prior to being named chair, 13% (n = 14) had a PhD, 4% (n = 4) had an MBA, and 23% (n = 24) were awarded a National Institutes of Health R01 grant, tendencies that were stable over time (p = 0.09–0.23), although when additional degrees were analyzed as a binary variable, chairs hired in 2010 or after were more likely to have an MBA and/or PhD versus those hired before 2010 (26% vs 10%, p = 0.04). The 3 most common residency programs attended by the neurosurgery chairs were Massachusetts General Hospital (n = 8, 8%), University of California, San Francisco (n = 8, 8%), and University of Michigan (n = 6, 6%). Most chairs (n = 63, 61%) attended residency at the institution and/or were staff at the institution before they were named chair, a tendency that persisted over time (p = 0.86).
CONCLUSIONS
Most neurosurgery department chairs matriculated into the position before the age of 50 years and, despite selection processes usually involving a national search, most chairs had a previous affiliation with the department, a phenomenon that has been relatively stable over time. In recent years, a large increase has occurred in the proportion of chairs with additional advanced degrees and more extensive research experience, underscoring how neurosurgical leadership has come to require scientific skills and the ability to procure grants, as well as the financial skills needed to navigate the ever-changing financial health care landscape.
Arman Jahangiri, Patrick M. Flanigan, Maxine Arnush, Ankush Chandra, Jonathan W. Rick, Sarah Choi, Alvin Chou, Mitchel S. Berger, and Manish K. Aghi
OBJECTIVE
Neurosurgeons play an important role in advancing medicine through research, the funding of which is historically linked to the National Institutes of Health (NIH). The authors defined variables associated with neurosurgical NIH funding, prevalence of funded topics by neurosurgical subspecialty, and temporal trends in NIH neurosurgical funding.
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The authors conducted a retrospective review of NIH-funded American Association of Neurological Surgeons members using NIH RePORTER (http://report.nih.gov/) for the years 1991–2015.
RESULTS
The authors followed 6515 neurosurgeons from 1991 to 2015, including 6107 (94%) non–MD-PhD physicians and 408 (6%) MD-PhDs. NIH grants were awarded to 393 (6%) neurosurgeons, with 23.2% of all first-time grants awarded to the top 5 funded institutions. The average total funded grant-years per funded neurosurgeon was 12.5 (range 1–85 grant-years). A higher percentage of MD-PhDs were NIH funded than MDs (22% [n = 91] vs 5% [n = 297], p < 0.0001). The most common grants awarded were R01 (128, 33%), K08 (69, 18%), F32 (60, 15%), M01 (50, 13%), and R21 (39, 10%). F32 and K08 recipients were 9-fold (18% vs 2%, p < 0.001) and 19-fold (38% vs 2%, p < 0.001) more likely to procure an R01 and procured R01 funding earlier in their careers (F32: 7 vs 12 years after residency, p = 0.03; K08: 9 vs 12 years, p = 0.01). Each year, the number of neurosurgeons with active grants linearly increased by 2.2 (R2= 0.81, p < 0.001), whereas the number of total active grants run by neurosurgeons increased at nearly twice the rate (4.0 grants/year) (R2= 0.91, p < 0.001). Of NIH-funded neurosurgical grants, 33 (9%) transitioned to funded clinical trial(s). Funded neurosurgical subspecialties included neuro-oncology (33%), functional/epilepsy (32%), cerebrovascular (17%), trauma (10%), and spine (6%). Finally, the authors modeled trends in the number of active training grants and found a linear increase in active R01s (R2= 0.95, p < 0.001); however, both F32 (R2= 0.36, p = 0.01) and K08 (R2= 0.67, p < 0.001) funding had a significant parabolic rise and fall centered around 2003.
CONCLUSIONS
The authors observed an upward trend in R01s awarded to neurosurgeons during the last quarter century. However, their findings of decreased K08 and F32 training grant funding to neurosurgeons and the impact of these training grants on the ultimate success and time to success for neurosurgeons seeking R01 funding suggests that this upward trend in R01 funding for neurosurgeons will be difficult to maintain. The authors’ work underscores the importance of continued selection and mentorship of neurosurgeons capable of impacting patient care through research, including the MD-PhDs, who are noted to be more represented among NIH-funded neurosurgeons.
杰弗里·w·陈,马丁·g·麦rchis R. Bhandarkar, Patrick M. Flanigan, Nikita Lakomkin, Anthony L. Mikula, Giorgos D. Michalopoulos, and Mohamad Bydon
OBJECTIVE
Proximal junctional kyphosis (PJK) is a complication of surgical management for adult spinal deformity (ASD) with a multifactorial etiology. Many risk factors are controversial, and their relative importance is not fully understood. The authors aimed to elucidate the association between bone mineral density (BMD) and PJK.
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A systematic literature search was performed using PubMed and Web of Science keywords of "Proximal Junctional Kyphosis [MeSH] OR Proximal Junctional Failure [MeSH]" AND "Bone Mineral Density [MeSH] OR Hounsfield Units [MeSH] OR DEXA [MeSH]" set to the date range of January 2002 to July 2022. Studies required a minimum of 10 patients and 12 months of follow-up. Articles were included if they were in the English language and presented a primary retrospective cohort that included a comparison of patients with and without PJK, as well as a radiographic biomarker for BMD, such as Hounsfield units (HU) or T-score.
RESULTS
A total of 18 unique studies with 2185 patients who underwent ASD surgery were identified. Of these, 537 patients (24.6%) developed PJK. Eight studies provided T-scores that were amenable to comparison, which found that patients who developed PJK were found to have lower BMD T-scores by a mean of −0.69 (95% CI −0.88 to −0.50; I2= 63.9%, p < 0.001). The HU at the UIV among patients with the PJK group (n = 101) compared with the non-PJK group (n = 156) was found to be significantly lower (mean difference −32.35, 95% CI −46.05 to −18.65; I2= 28.7%, p < 0.001).
CONCLUSIONS
This meta-analysis suggests that low preoperative BMD as measured by T-score and a diagnosis of osteoporosis were associated with higher postoperative PJK. Additionally, lower HU on CT at the UIV were found to be significant risk factors for postoperative PJK as well. These findings suggest that more attention to preoperative BMD is a risk factor for PJK among ASD patients is warranted.
Patrick M. Flanigan, Anthony L. Mikula, Pierce A. Peters, Soliman Oushy, Jeremy L. Fogelson, Mohamad Bydon, Brett A. Freedman, Arjun S. Sebastian, Bradford L. Currier, Ahmad Nassr, Kurt A. Kennel, Paul A. Anderson, David W. Polly, and Benjamin D. Elder
OBJECTIVE
Opportunistic Hounsfield unit (HU) determination from CT imaging has been increasingly used to estimate bone mineral density (BMD) in conjunction with assessments from dual energy x-ray absorptiometry (DXA). The authors sought to compare the effect of teriparatide on HUs across different regions in the pelvis, sacrum, and lumbar spine, as a surrogate measure for the effects of teriparatide on lumbosacropelvic instrumentation.
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A single-institution retrospective review of patients who had been treated with at least 6 months of teriparatide was performed. All patients had at least baseline DXA as well as pre- and post-teriparatide CT imaging. HUs were measured in the pedicle, lamina, and vertebral body of the lumbar spine, in the sciatic notch, and at the S1 and S2 levels at three different points (ilium, sacral body, and sacral ala).
RESULTS
Forty patients with an average age of 67 years underwent a mean of 20 months of teriparatide therapy. Mean HUs of the lumbar lamina, pedicles, and vertebral body were significantly different from each other before teriparatide treatment: 343 ± 114, 219 ± 89.2, and 111 ± 48.1, respectively (p < 0.001). Mean HUs at the S1 level for the ilium, sacral ala, and sacral body were also significantly different from each other: 124 ± 90.1, −10.7 ± 61.9, and 99.1 ± 72.1, respectively (p < 0.001). The mean HUs at the S2 level for the ilium and sacral body were not significantly different from each other, although the mean HU at the sacral ala (−11.9 ± 52.6) was significantly lower than those at the ilium and sacral body (p = 0.003 and 0.006, respectively). HU improvement occurred in most regions following teriparatide treatment. In the lumbar spine, the mean lamina HU increased from 343 to 400 (p < 0.001), the mean pedicle HU increased from 219 to 242 (p = 0.04), and the mean vertebral body HU increased from 111 to 134 (p < 0.001). There were also significant increases in the S1 sacral body (99.1 to 130, p < 0.05), S1 ilium (124 vs 165, p = 0.01), S1 sacral ala (−10.7 vs 3.68, p = 0.04), and S2 sacral body (168 vs 189, p < 0.05).
CONCLUSIONS
There was significant regional variation in lumbar and sacropelvic HUs, with most regions significantly increasing following teriparatide treatment. The sacropelvic area had lower HU values than the lumbar spine, more regional variation, and a higher degree of correlation with BMD as measured on DXA. While teriparatide treatment resulted in HUs > 110 in the majority of the lumbosacral spine, the HUs in the sacral ala remained suggestive of severe osteoporosis, which may limit the effectiveness of fixation in this region.
