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Encouraging early time of discharge (TOD) for medical inpatients is commonplace and may potentially improve patient throughput. It is unclear, however, whether early TOD after elective spine surgery achieves this goal without a consequent increase in re-presentations to the hospital.To evaluate whether early TOD results in increased rates of hospital readmission or return to the emergency department after elective anterior cervical spine surgery.We analyzed 686 patients who underwent elective uncomplicated anterior cervical spine surgery at a single institution. Logistic regression was used to evaluate the relationship between sociodemographic, procedural, and discharge characteristics, and the outcomes of readmission or return to the emergency department and TOD.In multiple logistic regression, TOD was not associated with increased risk of readmission or return to the emergency department within 30 days of surgery. Weekend discharge (odds ratio [OR] 0.33, 95% CI 0.21-0.53), physical therapy evaluation (OR 0.44, 95% CI 0.28-0.71), and occupational therapy evaluation (OR 0.32, 95% CI 0.17-0.63) were all significantly associated with decreased odds of discharge before noon. Disadvantaged status, as measured by area of deprivation index, was associated with increased odds of readmission or re-presentation (OR 1.86, 95% CI 0.95-3.66), although this result did not achieve statistical significance.There does not appear to be an association between readmission or return to the emergency department and early TOD after elective spine surgery. Overuse of inpatient physical and occupational therapy consultations may contribute to decreased patient throughput in surgical admissions.

Background Carotid endarterectomy (CEA) and carotid artery stenting (CAS) represent options to treat many patients with carotid stenosis. Although randomized trial data are plentiful, estimated rates of morbidity and mortality for both CEA and CAS have varied substantially. Objective To evaluate rates of adverse outcomes after CAS and CEA in a large national database. Methods We analyzed 84 191 adult patients undergoing elective, nonemergent CAS (n = 81 361) or CEA (n = 2830), from 2011 to 2018, in the American College of Surgeons' National Surgical Quality Improvement Program database. Odds of adverse outcomes (30-d rates of stroke, myocardial infarction (MI), cardiac arrest, prolonged length of stay (LOS), readmission, reoperation, and mortality) were evaluated in propensity-matched (n = 2821) cohorts through logistic regression. Results In the propensity-matched cohorts, CAS had increased odds of periprocedural stroke (odds ratio [OR] 1.97, 95% CI 1.32-2.95) and decreased odds of cardiac arrest (OR 0.33, 95% CI 0.13-0.84) and 30-d reoperation (OR 0.59, 95% CI 0.44-0.80) compared to CEA. Relative odds of MI, prolonged LOS, discharge to destination other than home, 30-d readmission, or 30-d mortality were statistically similar. In the unmatched patient population, rates of adverse outcomes with CEA were constant over time; however, for CAS, rates of stroke increased over time. In both the matched and unmatched patient cohorts, patients 70 yr and older had lower rates of post-procedural stroke with CEA, but not with CAS, compared to younger patients. Conclusion In a propensity-matched analysis of a large, prospectively collected, national, surgical database, CAS was associated with increased odds of periprocedural stroke, which increased over time. Rates of MI and death were not significantly different between the 2 procedures.

Retrospective analysis of the Nationwide Inpatient Sample, 2005-2011.To identify trends in procedural volume and rates in the time period surrounding publication of randomized controlled trials (RCTs) that examined the utility of vertebroplasty and kyphoplasty.Vertebroplasty and kyphoplasty are frequently performed for vertebral compression fractures. Several RCTs have been published with conflicting outcomes regarding pain and quality of life compared with nonsurgical management and sham procedures. Four RCTs with discordant results were published in 2009.The Nationwide Inpatient Sample provided longitudinal, retrospective data on United States' inpatients between 2005 and 2011. Inclusion was determined by a principal or secondary International Classification of Diseases, Ninth Revision, Clinical Modification code of 81.65 (percutaneous vertebroplasty) or 81.66 (percutaneous vertebral augmentation; "kyphoplasty"). No diagnoses were excluded. Years were stratified as "pre" (2005-2008) and "post" (2010-2011) in relation to the 4 RCTs published in 2009. Patient, hospital, and admission characteristics were compared using Pearson χ test.The estimated annual inpatient procedures performed decreased from 54,833 to 39,832 in the pre and post periods, respectively. The procedural rate for fractures decreased from 20.1% to 14.7% (P0.0001). Patient and hospital demographics did not change considerably between the time periods. In the post period, weekend admissions increased (34.2% vs. 12.4%, P0.0001), elective admissions decreased (21.4% vs. 40.0%, P0.0001), routine discharge decreased (33.0% vs. 52.1%, P0.0001), and encounters with ≥3 Elixhauser comorbidities increased (54.5% vs. 39.1%, P0.0001).The absolute rate of inpatient vertebroplasty and kyphoplasty procedures for fractures decreased 5% in the period (2010-2011) following the publication of 4 RCTs in 2009. The proportion of elective admissions and routine discharges decreased, possibly indicating a population with greater disease severity. Although our analysis cannot demonstrate a cause-and-effect relationship, the decreased inpatient volume and procedural rates surrounding the publication of sentinel negative RCTs is clearly observed.

Study design A retrospective cohort analysis of prospectively collected clinical data. Objective The aim of this study was to assess the effect of race on outcomes in patients undergoing elective laminectomy and/or fusion spine surgery. Summary of background data Studies that have looked at the effect of race on spine surgery outcomes have failed to take into account baseline risk factors that may influence peri-operative outcomes. Methods We identified 48,493 adult patients who underwent elective spine surgery consisting of elective laminectomy and/or fusion, from 2006 to 2012, at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP), a prospectively collected, national clinical database with established reproducibility and validity. Pre- and intraoperative characteristics and 30-day outcomes were stratified by race. We used propensity scores to match African-American and Caucasian patients on all pre- and intraoperative factors, including by principal diagnosis leading to surgery as well as surgery performed. We used regular and conditional logistic regression to predict the effect of race on adverse postoperative outcomes in the full sample and matched sample. Results Caucasians comprised 82% of our sample. We found no differences in the incidence of pre- and intraoperative factors when comparing Caucasian patients with all minority patients, and only minimal increased odds for prolonged length of length of hospitalization (LOS) and discharge with continued care. However, African-American patients, who comprised 39% of our minority sample, had more preoperative comorbidities than Caucasian patients. Even after eliminating all differences between pre- and intraoperative factors between Caucasian and African-American patients, African-American patients continued to have LOS that was, on average, one day longer than Caucasian patients. African-American patients also had higher odds for major complications [odds ratio (OR) = 1.3; 95% confidence interval (95% CI) 1.1-1.6], and to be discharged requiring continued care (OR = 2.3; 95% CI 1.8-2.8). Conclusion African-American race is independently associated with prolonged LOS, major complications, and a need to be discharged with continued care in patients undergoing elective spine surgery. Level of evidence 3.

BACKGROUND Surgery followed by adjuvant radiotherapy is a well-established treatment paradigm for brain metastases. OBJECTIVE To examine the effect of postsurgical whole-brain radiotherapy (WBRT) or localized radiotherapy (LRT), including stereotactic radiosurgery and intraoperative radiotherapy, on the rate of recurrence both local and distal to the resection site in the treatment of brain metastases. METHODS We retrospectively identified patients who underwent surgery for brain metastasis at the Cleveland Clinic between 2004 and 2012. Institutional review board-approved chart review was conducted, and patients who had radiation before surgery, who had nonmetastatic lesions, or who lacked postadjuvant imaging were excluded. RESULTS The final analysis included 212 patients. One hundred fifty-six patients received WBRT, 37 received stereotactic radiosurgery only, and 19 received intraoperative radiotherapy. One hundred forty-six patients were deceased, of whom 60 (41%) died with no evidence of recurrence. Competing risks methodology was used to test the association between adjuvant modality and progression. Multivariable analysis revealed no significant difference in the rate of recurrence at the resection site (hazard ratio [HR] 1.46, P = .26) or of unresected, radiotherapy-treated lesions (HR 1.70, P = .41) for LRT vs WBRT. Patients treated with LRT had an increased hazard of the development of new lesions (HR 2.41, P < .001) and leptomeningeal disease (HR 2.45, P = .04). Median survival was 16.5 months and was not significantly different between groups. CONCLUSION LRT as adjuvant treatment to surgical resection of brain metastases is associated with an increased rate of development of new distant metastases and leptomeningeal disease compared with WBRT, but not with recurrence at the resection site or of unresected lesions treated with radiation.

STUDY DESIGN Observational retrospective cohort study of prospectively collected database. OBJECTIVE To determine whether overweight body mass index (BMI) influences 30-day outcomes of elective spine surgery. SUMMARY OF BACKGROUND DATA Obesity is prevalent in the United States, but its impact on the outcome of elective spine surgery remains controversial. METHODS We used National Surgical Quality Improvement Program, a prospective clinical database with proven validity and reproducibility consisting of 256 perioperative standardized variables from surgical patients at nearly 400 academic and nonacademic hospitals nationwide. We identified 49,314 patients who underwent elective fusion, laminectomy or both between 2006 and 2012. We divided patients according to BMI (kg/m2) as normal (18.5-24.9), preobese (25.0-29.9), obese I (30.0-34.9), obese II (35.0-39.9), and obese III (≥40). Relationship between increased BMI and outcome of surgery measured as prolonged hospitalization, complications, return to the operating room, discharged with continued care requirement, readmission, and death was determined using logistic regression before and after propensity score matching. RESULTS All overweight patients (BMI ≥25 kg/m2) showed increased odds of an adverse outcome compared with normal patients in unmatched analyses, with maximal effect seen in obese III group. In the propensity-matched sample, obese III patients continued to show increased odds for complications (odds ratio, 1.6; 95% confidence interval, 1.1-2.3), readmission (odds ratio, 2.3; 95% confidence interval, 1.1-4.9), and return to the operating room (odds ratio, 1.8; 95% confidence interval, 1.1-3.1). CONCLUSION Impact of obesity on elective spine surgery outcome is mediated, at least in part, by comorbidities in patients with BMI between 25.0 and 39.9 kg/m2. However, BMI itself is an independent risk factor for adverse outcomes in morbidly obese patients. LEVEL OF EVIDENCE 3.

Study design Retrospective analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement database. Objective We assessed whether preoperative cigarette smoking and smoking duration predicted adverse, early, perioperative outcomes in patients undergoing elective spine surgery. Summary of background data Prior studies have assessed the association of smoking and long-term outcomes for a number of spine surgery procedures, with conflicting findings. The association between smoking and 30-day outcomes for spine surgery is unknown. Methods A total 14,500 adults, classified as current (N = 3914), prior (N = 2057), and never smokers. Using propensity scores, current and prior smokers were matched to never smokers. Logistic regression was used to predict adverse postoperative outcomes. The relationship between pack-years and adverse outcomes was tested. Sensitivity analyses were conducted limiting the study sample to patients who underwent spine fusion (N = 4663), and using patient subgroups by procedure. Results In unadjusted analyses, prior smokers were significantly more likely to have prolonged hospitalization (1.2, 95% confidence interval [CI]: 1.1-1.3) and major complications (1.3, 95% CI: 1.1-1.6) compared with never smokers. No association was found between smoking status and adverse outcomes in adjusted, matched patient models. Current smokers with more than 60 pack-years were more likely to die within 30 days of surgery (3.0, 95% CI, 1.1-7.8), compared with never smokers. Sensitivity analyses confirmed these findings. Conclusion The large National Surgical Quality Improvement population was carefully matched for a wide range of baseline comorbidities, including 29 variables previously suggested to influence perioperative outcomes. Although previous studies conducted in subgroups of spine surgery patients have suggested a deleterious effect for smoking on long-term outcomes in patients undergoing spine surgery, our analysis did not find smoking to be associated with early (30 d) perioperative morbidity or mortality.

Study design Analysis of the prospectively collected American College of Surgeons National Surgical Quality Improvement Program database. Objective To assess whether preoperative anemia predicted adverse, early, perioperative outcomes in patients undergoing elective spine surgery. Summary of background data Prior studies have assessed the association of anemia with outcomes in various noncardiac surgical procedures. The association between preoperative anemia and 30-day outcomes for spine surgery is unknown. Methods A total of 24,473 adults, classified as having severe (N = 88), moderate (N = 314), mild (N = 5477), and no anemia. Using propensity scores, patients with severe, mild, and moderate anemia were matched with patients with no anemia. Logistic regression was used to predict adverse postoperative outcomes. Sensitivity analyses were conducted limiting the study sample to patients who did not receive intra- or postoperative transfusion and to patients with and without preoperative cardiovascular comorbidities. Results Patients with all levels of anemia had significantly higher risk of nearly all adverse outcomes than nonanemic patients in unadjusted and propensity-matched models. Patients with moderate and mild anemia were more likely to have prolonged length of hospitalization, experience 1 or more complications, and expire within 30 days of surgery compared with nonanemic patients. The association between anemia and adverse outcomes was found independently of intra- and postoperative transfusions, and was not more pronounced in patients with preoperative cardiovascular comorbidities. Conclusion All levels of anemia were significantly associated with prolonged length of hospitalization and poorer operative or 30-day outcomes in patients undergoing elective spine surgery. Our findings, using a large multi-institutional sample of prospectively collected data, suggests that anemia should be regarded as an independent risk factor for perioperative and postoperative complications that deserves attention prior to elective spine surgery.

Research examining the process of deciding between treatment alternatives, the applicability of the existing literature to this process, and the way that this knowledge can be applied to inform clinical decisions is termed comparative effectiveness research (CER). Despite its emerging role in both clinical medicine and public policy, many neurosurgeons are unaware of the history of CER, the principles fundamental to its implementation, and the nature and extent to which it impacts patient care. We present a review of literature that provides a brief history of the evolution of CER, an overview of its scientific, financial, and public policy implications, and a discussion of its implementation and potential significance in modern clinical practice. We discuss how CER seeks to combine treatment efficacy data with quality of life, outcomes, and other forms of effectiveness data to guide selection of optimal patient management strategies. This research paradigm strengthens the final step in clinical research that should follow the traditional demonstration of efficacy and reemphasizes the potentially important role of observational and retrospective investigations in establishing effectiveness of efficacious procedures in actual application to individual patients. It is useful for neurosurgeons to understand the CER model, because it occupies an emerging role in both clinical medicine and public policy and presents a potentially useful model for informing medical decision-making in the type of real-world situations commonly encountered by clinical neurosurgeons.

BACKGROUND: Observational methods can be used in conjunction with the comparative effectiveness research (CER) paradigm to inform decisions between alternative patient management strategies in real-world clinical settings. OBJECTIVE: To present a brief review of current observational research regarding 3 strategies for predicting normal hypothalamic-pituitary-adrenal (HPA) axis function after surgical resection of pituitary tumors and to apply the CER model to compare these management alternatives. METHODS: We designed and conducted 2 prospective observational studies involving 183 patients undergoing microsurgical resection for pituitary tumors. These investigations yielded a comprehensive database comprising longitudinal data from multiple clinical domains. We investigated 3 potential strategies to predict normal postoperative HPA axis function in this cohort, including preoperative adrenocorticotrophic hormone stimulation testing and measurement of serum cortisol levels immediately after surgery or on the first postoperative day. We performed a focused comparative effectiveness review to help inform the decision between the 3 potential clinical management strategies. RESULTS: This investigation illustrates the use of observational research methods in conjunction with CER methodology as one means of informing clinical management decisions. Of the 3 strategies for assessing postoperative HPA axis function studied, preoperative and immediate postoperative adrenocorticotrophic hormone stimulation testing had the highest sensitivity, accuracy, and positive predictive value for normal HPA axis function postoperatively. The preoperative strategy was also the most cost-effective approach (12% reduction vs benchmark). CONCLUSION: The decision to use any of the 3 strategies outlined requires attention to a specific patient's clinical situation, but this decision may be aided by the results of this CER analysis.

Overexpression of Aurora B kinase, which regulates cell progression through mitosis and cytokinesis, has been shown to be associated with higher-grade tumors and shortened survival in astrocytomas. Aurora B expression was evaluated by immunohistochemistry in 32 ependymomas, 10 anaplastic ependymomas, 16 myxopapillary ependymomas, and 9 subependymomas. Aurora B expression was identified in 20 (62.5%) ependymomas, 5 (50%) anaplastic ependymomas, 1 (6.3%) myxopapillary ependymoma, and no subependymomas. The association between Aurora B expression and World Health Organization grade II/III tumors was statistically significant (P

OBJECTIVE: Adult gliomas have indistinct borders. As the ratio of neoplastic cells to normal cells becomes lower, the ability to detect these cells diminishes. We describe a device designed to augment intraoperative identification of both solid tumor and infiltrating tumor margins. METHODS: A novel, intraoperative, optical spectroscopic tool, using both white light reflectance and 337-nm excitation fluorescence spectroscopy, is described. Discrimination algorithms have been developed to segregate neoplastic tissues from normal glial and neuronal elements. The spectroscopy device was used to measure 5 to 10 locations during glioma resection. Beneath the tool, a biopsy sample was obtained and the pathological results were reviewed in a blinded fashion. Samples were classified as solid tumor, infiltrating tumor, or normal gray or white matter. Comparisons were made between the optical spectra and the histopathological results of sampled areas in evaluating the sensitivity and specificity of the tool for tissue discrimination. RESULTS: Spectral data were obtained from 24 patients with glioma and from 11 patients with temporal lobe epilepsy. A sensitivity of 80% and a specificity of 89% in discriminating solid tumor from normal tissues were obtained. In addition, infiltrating tumor margins were distinguished from normal tissues with a sensitivity of 94% and a specificity of 93%. CONCLUSION: We have developed a handheld, optical spectroscopic device that may be used rapidly and in near real time with high sensitivity and reproducibility as an optical tissue discrimination tool in glioma surgery.

OBJECTIVE: Magnetic resonance imaging abnormalities in malignant brain tumors after irradiation may represent either recurrent tumor or radiation injury. Optical spectroscopy may represent a novel technique to identify radiation damage in brain tissues and to differentiate contrast-enhancing lesions from recurrent tumor. METHODS: Fluorescence and diffuse reflectance spectra were acquired from 90 patients: 15 undergoing surgical resection for presumed recurrent tumor after radiation therapy, 15 with epilepsy and hippocampal sclerosis, and 60 with tumors who had not received irradiation. Optical spectra were acquired from 6 to 10 sites and were compared with a biopsy obtained from beneath the optical spectroscopy probe; the data then were classified by a neuropathologist blinded to the spectroscopy data. A probe for the intraoperative collection of diffuse reflectance and fluorescence spectra was used. RESULTS: Thirteen of 15 patients (29 of 129 spectra) with previous irradiation showed a unique spectral feature characterized by a fluorescence peak centered at 500 nm (F500). All biopsy specimens showing histopathological signs of radiation injury had the F500 on their corresponding spectra (18 of 18). The F500 was identified in another 10% (11 of 111 spectra) of samples with previous irradiation but no histologically identifiable signs of radiation damage. The F500 was never seen in the normal temporal lobe of epilepsy patients with hippocampal sclerosis (0 of 105) and was seen in only 1.5% of tumor patients who did not undergo previous irradiation (6 of 433). CONCLUSION: Optical spectroscopy detects radiation damage in brain tissues. The F500 spectral peak may allow accurate selection of tissues for biopsy in evaluating patients with new, contrast-enhancing lesions in the setting of previous irradiation.

Described is a patient with concurrent discrete gliomas: a pleomorphic xanthoastrocytoma with anaplastic features and an anaplastic oligoastrocytoma. The distinct and morphologically dissimilar tumors demonstrated similar genetic abnormalities by loss of heterozygosity and comparative genome hybridization. Clonality and proteomic analyses highlighted an independent origin for the two tumors. Proteomic methods may prove useful in cases where the differential diagnosis and pathogenetic origin of tumors are uncertain, as well as more globally for its ability to provide insight into specific expression of proteins that may serve as unique markers of tumorigenesis or as novel targets of therapy.

STUDY DESIGN Retrospective study of 184 autologous iliac crest bone grafts used for anterior cervical fusion in 144 procedures. OBJECTIVES To evaluate the effect of autologous iliac crest bone graft harvest site on operation and recovery and to identify patients at risk for harvest morbidity. SUMMARY OF BACKGROUND DATA Although autologous iliac crest bone graft is considered the most successful grafting material, concerns about harvest morbidity provide a rationale for considering allograft. Data about the use of autograft therefore would assist spinal surgeons in selecting the appropriate substrates for fusion after anterior cervical decompression. METHODS Statistical analysis based on patient gender, smoking history, obesity, and medical or pharmacologic risk factors for wound healing was used to evaluate morbidity after patient interviews and examinations. Limited assessment of radiographic outcome also was performed. RESULTS A second operation because of donor site morbidity was performed in four patients (2.8%), but only one (0.7%) with meralgia paresthetica had permanent sequelae. Superficial wound infection or dehiscence occurred in 5.6% of patients, with a disproportionate number of women, obese patients, and those with medical risk represented. Protracted wound symptoms of pain and poor cosmesis were reported in 2.8% and 3.5% of patients, respectively, and also were found in a significant number of female and obese patients. Evidence of fusion was present in 97% of cases. CONCLUSION Autologous iliac crest bone graft harvest results in minimal major morbidity when regional anatomy is respected and careful technique is observed. The identification of patients at risk for minor complications suggests that allograft may be appropriate in these patients; however, prospective comparison is required to identify whether graft material or technical factors determine fusion success and relative benefit.

As many as 5 to 10% of cases presented for pathologic review pose a significant diagnostic dilemma. Among the most challenging of these are different lesions with similar clinicopathologic features.1 Whereas modern methods such as immunohistochemistry and molecular tools such as the PCR can help distinguish some conditions, there remain lesions, such as tumors, that share the same genetic alterations but for which differentiation remains imperative for prognostic and therapeutic reasons. A setting in which this may be especially true is in familial, multiple neoplastic syndromes, in which tumors may share histologic features and also have an identical pathogenesis. von Hippel–Lindau (vHL) disease is a hereditary cancer syndrome characterized by multiple tumors of the CNS and retina, kidney, adrenal medulla, and pancreas. Although CNS hemangioblastomas (Hb) are considered benign, renal clear cell carcinomas (RCCC) frequently metastasize and are the cause of death in up to 30% of vHL patients.2,3⇓ Given the morphologic resemblance of …

Image-guided neurosurgical techniques have been developed to provide additional spatial reference during surgery. In the past, these positional cues have been provided by correlating a three-dimensional (3D) digitized point within patient space (touching the brain surface with a stylus) to the corresponding point within image space (usually simultaneously rendered on three orthogonal/cardinal slices and one isometric view of the preoperative image volume). Complementary technologies have been created to improve landmark recognition, which include multimodal image fusion, modifications to operating microscopes, virtual head-mounted displays, and enhanced-reality visualization, among others (4, 6–10, 12, 16, 25, 31, 33). Although an impressive myriad of technology has been developed, there has been little quantitative documented benefit with respect to outcome or improved surgical performance. Whereas texturing laser range scanning (tLRS) technology could be seen as another in a list of these innovations, tLRS may have greater potential in that it may facilitate compensation for intraoperative tissue deformation during image-guided surgery (IGS), i.e., the brain shift problem (18, 20). Combined with the low cost of laser optics and charge-coupling device (CCD) arrays, tLRS technology presents an interesting adjunct for IGS work. In brief, a tLRS system passes a laser stripe over the surface of interest while collecting the reflected light with a high-resolution CCD camera. Through the process of triangulation, the data acquired can be interpreted to reconstruct the 3D surface as a cloud of digitized points. The “texturing” nomenclature refers to a relatively novel feature whereby a second digital image of the field of view (FOV) is acquired at the time of scanning and is subsequently mapped to the 3D geometric point cloud. As a result, a representation of data is captured that contains both geometric and intensity information, i.e., a “textured” brain surface, the shape and visual features of which are associated with the FOV. Textured surfaces can provide many cues that aid in object recognition and localization, including information about depth, curvature, the orientation of surfaces, and distances between object features (23). For example, the benefit of adding texture to shape information in the field of face recognition is well established (3, 21, 22, 29). Except for some limited studies using vessel bifurcations for image-to-patient registration and point-based brain shift measurement (19, 24), cortical surface texture methods have not been studied with respect to neurosurgical navigation. Nonetheless, several findings from face recognition research may apply to neuronavigation. One of the most important of these is that the recognition speed of features can be enhanced by texture. Similarly, the orientation of the textured surface is important and it may be favorable to use tLRS displays that are reflective of an egocentric reference relevant to the viewer (29, 30). Furthermore, animation and dynamic viewing may be important enhancements for recognition. With respect to visualizing brain shift, it may be more effective for a surgeon to see a dynamic rendering of the tLRS cortical surface to appreciate the degree of motion (11, 13). Given the localized, feature-rich nature of the brain surface (i.e., non-diffuse features), the use of tLRS data should reduce view-point dependencies. Despite the abundance of recognition research performed, previous work does not entirely apply to IGS visualization. The alignment of cortical tLRS data to a segmented magnetic resonance (MR) grayscale encoded volume rendering of the brain represents two completely different visual modalities. The difference in the geometric and textural representation of these surfaces requires an inherent pattern recognition task that is significantly different. Another dissimilarity is that recognition experiments often involve a learning and testing phase in which the recognition objects contain the same localized features (e.g., geometric structures of subjects do not change, only their pose). In IGS, the exposed cortical surface cannot be visualized before surgery and is markedly dissimilar in texture and appearance than the MR image counterpart (which can be studied preoperatively). This represents a fundamentally more challenging feature recognition task. However, this difficulty may be significantly offset by the level of expertise in the testing population (neurosurgeons). We conducted a clinical study to assess the extent to which tLRS technology can be used in the operative setting and report the utility of this unique data and the enhanced visualization it provides. We examined two points in this preliminary, prospective clinical study. First, we quantitatively examined a series of image-to-patient registrations in near real-time to assess the fidelity of this registration process. Second, we investigated whether our novel tLRS-to-MR image volume displays could enhance navigational and cortical surface recognition. Our findings suggest that tLRS technology may allow surgeons to better evaluate the fidelity of image-to-patient registration and that tLRS can accurately provide anatomic cues for cortical recognition assistance, which will provide for real-time assessment of intraoperative brain shift.

The gene defect for hereditary papillary renal carcinoma 1 (HPRC) has recently been mapped to chromosome 7q, and germline mutations of MET (also known as c-met) at 7q31 have been detected in patients with HPRC (ref. 2). Tumours from these patients commonly show trisomy of chromosome 7 when analysed by cytogenetic studies and comparative genomic hybridization 3 (CGH). However, the relationship between trisomy 7 and MET germline mutations is not clear. We studied 16 renal tumours from two patients with documented germline mutations in exon 16 of MET. Flourescent in situ hybridization (FISH) analysis showed trisomy 7 in all tumours. To determine whether the chromosome bearing the mutant or wild-type MET gene was duplicated, we performed duplex PCR and phosphoimage densitometry using polymorphic microsatellite markers D7S1801 and D7S1822, which were linked to the disease gene locus, and D1S1646 as an internal control. We determined the parental origin of chromosome alleles by genotyping parental DNA. In all 16 tumours there was an increased signal intensity (2:1 ratio) of the microsatellite allele from the chromosome bearing the mutant MET compared with the allele from the chromosome bearing the wild-type MET. Our study demonstrates a non-random duplication of the chromosome bearing the mutated MET in HPRC and implicates this event in tumorigenesis. All tumours analysed using FISH were trisomic for chromosome 7 using chromosome 7-specific painting and centromeric α-satellite probes (Fig. 1d). In addition, three copies of the MET gene were consistently detected in the tumour cells using cosmid c182b3 (which contains MET) as a probe (Fig. 1b). In contrast