A Pineal Parenchymal Tumor of Intermediate Differentiation in an Octogenarian Contains a Rare KBTBD4 Insertion.

Pineal parenchymal tumors are rare central nervous system tumors that pose diagnostic challenges for surgical pathologists. Due to their paucity, their clinicopathologic features are still being defined. We report an 86-year-old woman with a remote history of breast lobular carcinoma who presented with a 2-month neurologic history that included gait instability, blurry vision, and headaches. Magnetic resonance imaging revealed a lobular, heterogeneously enhancing pineal region mass compressing the aqueduct of Sylvius. A biopsy performed concomitant with endoscopic third ventriculostomy consisted of small sheets of cells with eosinophilic to clear cytoplasm, multipolar processes, and ovoid nuclei with stippled chromatin. Whole exome sequencing revealed a small in-frame insertion (duplication) in exon 4 of KBTBD4 (c.931_939dup, p.P311_R313dup/ p.R313_M314insPRR), which has very recently been reported in 2 pineal parenchymal tumors of intermediate differentiation (PPTID). Additionally, variants of uncertain significance in CEBPA (c.863G > C, p.R288P) and MYC (c.655T > C, p.S219P) were identified. Although PPTID is considered a disease of young adulthood, review of 2 institutional cohorts of patients with pineal region tumors revealed that 25% of individuals with PPTID were over 65 years of age. In conclusion, PPTID should be considered in the differential diagnosis of pineal region tumors in older adults.

Sensitizing brain metastases to stereotactic radiosurgery using hyperbaric oxygen: A proof-of-principle study.

PURPOSE: Increased oxygen levels may enhance the radiosensitivity of brain metastases treated with stereotactic radiosurgery (SRS). This project administered hyperbaric oxygen (HBO) prior to SRS to assess feasibility, safety, and response. METHODS: 38 patients were studied, 19 with 25 brain metastases treated with HBO prior to SRS, and 19 historical controls with 27 metastases, matched for histology, GPA, resection status, and lesion size. Outcomes included time from HBO to SRS, quality-of-life (QOL) measures, local control, distant (brain) metastases, radionecrosis, and overall survival. RESULTS: The average time from HBO chamber to SRS beam-on was 8.3 ± 1.7 minutes. Solicited adverse events (AEs) were comparable between HBO and control patients; no grade III or IV serious AEs were observed. Radionecrosis-free survival (RNFS), radionecrosis-free survival before whole-brain radiation therapy (WBRT) (RNBWFS), local recurrence-free survival before WBRT (LRBWFS), distant recurrence-free survival before WBRT (DRBWFS), and overall survival (OS) were not significantly different for HBO patients and controls on Kaplan-Meier analysis, though at 1-year estimated survival rates trended in favor of SRS + HBO: RNFS - 83% vs 60%; RNBWFS - 78% vs 60%; LRBWFS - 95% vs 78%; DRBWFS - 61% vs 57%; and OS - 73% vs 56%. Multivariate Cox models indicated no significant association between HBO treatment and hazards of RN, local or distant recurrence, or mortality; however, these did show statistically significant associations (p < 0.05) for: local recurrence with higher volume, radionecrosis with tumor resection, overall survival with resection, and overall survival with higher GPA. CONCLUSION: Addition of HBO to SRS for brain metastases is feasible without evident decrement in radiation necrosis and other clinical outcomes.

Association between interhospital transfer and increased in-hospital mortality in patients with spinal epidural abscesses.

BACKGROUND CONTEXT: Spinal epidural abscess (SEA) is an uncommon yet serious infection, associated with significant morbidity and mortality. Patients diagnosed with SEA often require surgical interventions or critical care services that are not available at community hospitals and are therefore transferred to tertiary care centers. Little is known about the effects of interhospital transfer on acute outcomes for patients with SEA. PURPOSE: To study the effects of interhospital transfer on acute outcomes for patients with SEA. STUDY DESIGN: Cross sectional analysis using the 2009 to 2017 National Inpatient Sample (NIS). PATIENT SAMPLE: Using the 2009 to 2017 NIS, we identified cases of SEA using ICD, Ninth, or Tenth Revision diagnosis codes 324.1 & G06.1. OUTCOME MEASURES: Our primary endpoint was in hospital mortality. METHODS: The association between interhospital transfer and inpatient mortality was assessed using multivariable logistic regression to adjust for potential covariates. Patient and hospital factors associated with interhospital transfer were assessed in a secondary analysis. RESULTS: A total of 21.5% of patient with SEA were treated after transfer from another hospital. After adjusting for covariates, those who presented after transfer had higher odds of death during hospitalization (OR: 1.51, 95% CI 1.27-1.78, p<.001). Transferred patients were significantly more likely to live in rural communities (11.4 % vs. 5.3 % for nontransferred patients). CONCLUSIONS: Interhospital transfer, which occurred more frequently in patients from rural hospitals, was associated with death even after controlling for disease severity. Addressing healthcare delivery disparities across the US, including across the rural-urban spectrum, will require better understanding of the observed increased mortality of interhospital transfer as a preventable source of in-hospital mortality for SEA.

Racial Disparities in Outcomes After Spine Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: Racial disparities are a major issue in health care but the overall extent of the issue in spinal surgery outcomes is unclear. We conducted a systematic review/meta-analysis of disparities in outcomes among patients belonging to different racial groups who had undergone surgery for degenerative spine disease. METHODS: We searched Ovid MEDLINE, Scopus, Cochrane Review Database, and ClinicalTrials.gov from inception to January 20, 2021 for relevant articles assessing outcomes after spine surgery stratified by race. We included studies that compared outcomes after spine surgery for degenerative disease among different racial groups. RESULTS: We found 30 studies that met our inclusion criteria (28 articles and 2 published abstracts). We included data from 20 cohort studies in our meta-analysis (3,501,830 patients), which were assessed to have a high risk of observation/selection bias. Black patients had a 55% higher risk of dying after spine surgery compared with white patients (relative risk [RR], 1.55, 95% confidence interval [CI], 1.28-1.87; I2 = 70%). Similarly, black patients had a longer length of stay (mean difference, 0.93 days; 95% CI, 0.75-1.10; I2 = 73%), and higher risk of nonhome discharge (RR, 1.63; 95% CI, 1.47-1.81; I2 = 89%), and 30-day readmission (RR, 1.45; 95% CI, 1.03-2.04; I2 = 96%). No significant difference was noted in the pooled analyses for complication or reoperation rates. CONCLUSIONS: Black patients have a significantly higher risk of unfavorable outcomes after spine surgery compared with white patients. Further work in understanding the reasons for these disparities will help develop strategies to narrow the gap among the racial groups.

Improving the Usability of 5-Aminolevulinic Acid Fluorescence-Guided Surgery by Adding an Optimized Secondary Light Source.

BACKGROUND: Tumors that take up and metabolize 5-aminolevulinic acid emit bright pink fluorescence when illuminated with blue light, aiding surgeons in identifying the margin of resection. The adoption of this method is hindered by the blue light illumination, which is too dim to safely operate under and therefore necessitates switching back and forth from white-light mode. The aim of this study was to examine the addition of an optimized secondary illuminant adapter to improve usability of blue-light mode without degrading tumor contrast. METHODS: Color science methods were used to evaluate the color of the secondary illuminant and its impact on color rendering index as well as the tumor-to-background color contrast in data collected from 7 patients with high-grade gliomas (World Health Organization grade III and IV). A secondary illuminant adapter was built to provide 475-600 nm light the intensity of which can be controlled by the surgeon and was evaluated in 2 additional patients. RESULTS: Secondary illuminant color had opposing effects on color rendering index and tumor-to-background color contrast; providing surgeon control of intensity allows this trade-off to be balanced in real time. Demonstration in 2 high-grade glioma cases confirms this, showing that additional visibility adds value when intensity can be controlled by the surgeon. CONCLUSIONS: Addition of a secondary illuminant may mitigate surgeon complaints that the operative field is too dark under the blue light illumination required for 5-aminolevulinic acid fluorescence guidance by providing improved color rendering index without completely sacrificing tumor-to-background color contrast.

False Localization of Ruptured Intracranial Dermoid Secondary to Subarachnoid Spread of Cyst Contents.

A 34-year-old right-handed female presented to the emergency department with a worsening headache, neck stiffness, intermittent abnormal sensation, and right arm weakness. Shortly after arrival, she had a generalized tonic-clonic seizure. A noncontrast head computed tomography scan revealed a right-sided, low-attenuating, lobulated mass ipsilateral to her arm symptoms. Magnetic resonance imaging revealed an abnormal signal throughout the subarachnoid space and increased fluid-attenuated inversion recovery sequence signal contralateral to the mass. This presentation suggested a false localization sign of sensory and motor disturbance ipsilateral to the mass likely caused by cyst rupture and sebum spread contralateral, causing cortical irritation (evidenced by increased fluid-attenuated inversion recovery sequence signal). During mass resection, sebum was visible throughout the subarachnoid space. The patient had an uneventful recovery from surgery and has been seizure free since the resection with steady improvement of symptoms. This case highlights the importance of avoiding cyst rupture of dermoid cysts.

Nervus Intermedius Symptoms following Surgical or Radiation Therapy for Vestibular Schwannoma.

OBJECTIVES: This study compares the functional outcomes of nevus intermedius impairment following surgery, radiation, or observation for the treatment of vestibular schwannoma. STUDY DESIGN: Retrospective cohort study. SETTINGS: Tertiary care medical center. SUBJECTS AND METHODS: We retrospectively examined 141 charts of patients with a vestibular schwannoma seen in the Dartmouth-Hitchcock Acoustic Neuroma Clinic between 2012 and 2014. Seventy-one patients underwent intervention (including radiation) as their primary treatment, and 70 were treated with observation. As part of routine care, patients were interviewed at clinic visits and with a questionnaire assessing nervus intermedius impairment. RESULTS: At presentation, 25 patients (19%) reported nervus intermedius impairment. Most common disturbances were xerophthalmia (dry eyes, 13%) and dysgeusia (taste alteration, 7.6%). Postintervention, 35 patients (53%) had ≥1 symptoms of nervus intermedius dysfunction, which is increased in comparison with patients in the observation group (17 patients, 26.5%, P < .05). Twelve intervention patients had symptoms resolve postoperatively, making no long-term difference between the observation and intervention groups (P = .20). Motor function of the facial nerve postoperatively is correlated with nervus intermedius symptoms. Surgical approaches were compared with radiation therapy, and no significant difference in nervus intermedius outcomes was found. CONCLUSION: This study demonstrates the clinical importance of monitoring nervus intermedius symptoms, since a high percentage of all patients undergoing intervention will be symptomatic during management. Patients with motor dysfunction are at a higher risk of developing nervus intermedius sequelae and need close follow-up. Although impairment is common, many symptoms will improve over time with no long-term difference between intervention patients and those under observation.

Utility of Routine Outpatient Cervical Spine Imaging Following Anterior Cervical Corpectomy and Fusion.

BACKGROUND: Construct failure is an uncommon but well-recognized complication following anterior cervical corpectomy and fusion (ACCF). In order to screen for these complications, many centers routinely image patients at outpatient visits following surgery. There remains, however, little data on the utility of such imaging. METHODS: The electronic medical record of all patients undergoing anterior cervical corpectomy and fusion at Dartmouth-Hitchcock Medical Center between 2004 and 2009 were reviewed. All patients had routine cervical spine radiographs performed perioperatively. Follow-up visits up to two years postoperatively were analyzed.  RESULTS: Sixty-five patients (mean age 52.2) underwent surgery during the time period. Eighteen patients were female. Forty patients had surgery performed for spondylosis, 20 for trauma, three for tumor, and two for infection. Forty-three patients underwent one-level corpectomy, 20 underwent two-level corpectomy, and two underwent three-level corpectomy, using an allograft, autograft, or both. Sixty-two of the fusions were instrumented using a plate and 13 had posterior augmentation. Fifty-seven patients had follow-up with imaging at four to 12 weeks following surgery, 54 with plain radiographs, two with CT scans, and one with an MRI scan. Unexpected findings were noted in six cases. One of those patients, found to have asymptomatic recurrent kyphosis following a two-level corpectomy, had repeat surgery because of those findings. Only one further patient was found to have abnormal imaging up to two years, and this patient required no further intervention. CONCLUSIONS: Routine imaging after ACCF can demonstrate asymptomatic occurrences of clinically significant instrument failure. In 43 consecutive single-level ACCF however, routine imaging did not change management, even when an abnormality was discovered. This may suggest a limited role for routine imaging after ACCF in longer constructs involving multiple levels.

Improving the quality of care for patients diagnosed with glioma during the perioperative period.

PURPOSE: Although there is agreement on the oncologic management of patients with glioma, few guidelines exist to standardize other aspects of care, including supportive care. METHODS: A quality improvement (QI) project was chartered to improve the care provided to patients with glioma. A multidisciplinary team was convened and identified 10 best-practice measures. Using a plan-do-study-act framework, the team brainstormed and implemented various improvement interventions between June 2011 and October 2012. Statistical process control charts were used to evaluate progress. A dashboard of quality measures was generated to allow for ongoing measurement and reporting. RESULTS: The retrospective assessment phase consisted of 43 patients with diagnosis of glioma. A manual medical record review for these patients showed that compliance with 10 best-practice measures ranged from 23% to 100%. Several factors contributed to less-than-ideal process performance, including poor communication among disciplines and lack of familiarity with the larger system of care. After implementing improvement interventions, performance was measured in 96 consecutive patients with glioma. The proportion of patients who met criteria for 10 practice measures significantly improved (pre-QI work, 63%; post-QI work, 85%; P = .003). The largest improvement was observed in the measure assessing for preoperative notification of the neuro-oncology program (pre-QI work, 39%; post-QI work, 97%; P < .001). CONCLUSION: QI principles were used by a multidisciplinary team to improve the quality of care for patients with glioma during the perioperative period. Leadership involvement, ongoing dialogue across departments, and reporting of system performance were important for sustaining process improvements.

Outpatient follow-up of nonoperative cerebral contusion and traumatic subarachnoid hemorrhage: does repeat head CT alter clinical decision-making?

OBJECTIVES: Many neurosurgeons obtain repeat head CT at the first clinic follow-up visit for nonoperative cerebral contusion and traumatic subarachnoid hemorrhage (tSAH). The authors undertook a single-center, retrospective study to determine whether outpatient CT altered clinical decision-making. METHODS: The authors evaluated 173 consecutive adult patients admitted to their institution from April 2006 to August 2012 with an admission diagnosis of cerebral contusion or tSAH and at least 1 clinic follow-up visit with CT. Patients with epidural, subdural, aneurysmal subarachnoid, or intraventricular hemorrhage, and those who underwent craniotomy, were excluded. Patient charts were reviewed for new CT findings, new patient symptoms, and changes in treatment plan. Patients were stratified by neurological symptoms into 3 groups: 1) asymptomatic; 2) mild, nonspecific symptoms; and 3) significant symptoms. Mild, nonspecific symptoms included minor headaches, vertigo, fatigue, and mild difficulties with concentration, short-term memory, or sleep; significant symptoms included moderate to severe headaches, nausea, vomiting, focal neurological complaints, impaired consciousness, or new cognitive impairment evident on routine clinical examination. RESULTS: One hundred seventy-three patients met inclusion criteria, with initial clinic follow-up obtained within approximately 6 weeks. Of the 173 patients, 104 (60.1%) were asymptomatic, 68 patients (39.3%) had mild, nonspecific neurological symptoms, and 1 patient (1.0%) had significant neurological symptoms. Of the asymptomatic patients, 3 patients (2.9%) had new CT findings and 1 of these patients (1.0%) underwent a change in treatment plan because of these findings. This change involved an additional clinic appointment and CT to monitor a 12-mm chronic subdural hematoma that ultimately resolved without treatment. Of the patients with mild, nonspecific neurological symptoms, 6 patients (8.8%) had new CT findings and 3 of these patients (4.4%) underwent a change in treatment plan because of these findings; none of these patients required surgical intervention. The single patient with significant neurological symptoms did not have any new CT findings. CONCLUSIONS: Repeat outpatient CT of asymptomatic patients after nonoperative cerebral contusion and tSAH is very unlikely to demonstrate significant new pathology. Given the cost and radiation exposure associated with CT, imaging should be reserved for patients with significant symptoms or focal findings on neurological examination.

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

BACKGROUND: The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE: To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS: ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS: Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION: ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

Mini-open stabilization of a sacral fracture: technical case report.

BACKGROUND AND IMPORTANCE: Comminuted sacral fractures present significant challenges for operative management. Open and percutaneous sacroiliac screws have been used for stabilization but carry not insignificant rates of complications, including wound infection for the former and malposition and neurological injury for the latter. We report the use of a novel mini-open lumbar-ilium fixation for stabilization of a patient with a comminuted sacral fracture. CLINICAL PRESENTATION: A 33-year-old man with intact neurologic function was admitted after a fall of approximately 25 ft. A comminuted sacral fracture was diagnosed. The patient was unable to tolerate conservative management because of pain in upright positions. The patient was taken to the operating room for stabilization with a "mini-open" procedure involving L4 and L5 pedicle screws and bilateral iliac screws. Four 2-in paramedian incisions were made overlying the L4-L5 facet joints and medial to the sacroiliac joints. Minimally invasive retractors were placed to expose bony landmarks. L4-L5 pedicle screws and bilateral iliac screws were placed with minimal fluoroscopic guidance. Titanium rods were tunneled inferior-superiorly between incisions and affixed to screw heads. Total operative time was approximately 3.5 hours. The patient remained neurologically intact and had an uncomplicated recovery. One-year follow-up computed tomography showed successful healing of the sacrum. CONCLUSION: We report the first case of a mini-open procedure to treat a comminuted sacral fracture. Use of this procedure offers a straightforward method for sacral stabilization with minimal blood loss and minimal radiation exposure. If indicated, this method could be combined with decompressive procedures.

Postoperative stereotactic radiosurgery without whole-brain radiation therapy for brain metastases: potential role of preoperative tumor size.

PURPOSE: Radiation therapy following resection of a brain metastasis increases the probability of disease control at the surgical site. We analyzed our experience with postoperative stereotactic radiosurgery (SRS) as an alternative to whole-brain radiotherapy (WBRT), with an emphasis on identifying factors that might predict intracranial disease control and overall survival (OS). METHODS AND MATERIALS: We retrospectively reviewed all patients through December 2008, who, after surgical resection, underwent SRS to the tumor bed, deferring WBRT. Multiple factors were analyzed for time to intracranial recurrence (ICR), whether local recurrence (LR) at the surgical bed or "distant" recurrence (DR) in the brain, for time to WBRT, and for OS. RESULTS: A total of 49 lesions in 47 patients were treated with postoperative SRS. With median follow-up of 9.3 months (range, 1.1-61.4 months), local control rates at the resection cavity were 85.5% at 1 year and 66.9% at 2 years. OS rates at 1 and 2 years were 52.5% and 31.7%, respectively. On univariate analysis (preoperative) tumors larger than 3.0 cm exhibited a significantly shorter time to LR. At a cutoff of 2.0 cm, larger tumors resulted in significantly shorter times not only for LR but also for DR, ICR, and salvage WBRT. While multivariate Cox regressions showed preoperative size to be significant for times to DR, ICR, and WBRT, in similar multivariate analysis for OS, only the graded prognostic assessment proved to be significant. However, the number of intracranial metastases at presentation was not significantly associated with OS nor with other outcome variables. CONCLUSIONS: Larger tumor size was associated with shorter time to recurrence and with shorter time to salvage WBRT; however, larger tumors were not associated with decrements in OS, suggesting successful salvage. SRS to the tumor bed without WBRT is an effective treatment for resected brain metastases, achieving local control particularly for tumors up to 3.0 cm diameter.

Tumor bed dynamics after surgical resection of brain metastases: implications for postoperative radiosurgery.

PURPOSE: To analyze 2 factors that influence timing of radiosurgery after surgical resection of brain metastases: target volume dynamics and intracranial tumor progression in the interval between surgery and cavity stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Three diagnostic magnetic resonance imaging (MRI) scans were retrospectively analyzed for 41 patients with a total of 43 resected brain metastases: preoperative MRI scan (MRI-1), MRI scan within 24 hours after surgery (MRI-2), and MRI scan for radiosurgery planning, which is generally performed ≤1 week before SRS (MRI-3). Tumors were contoured on MRI-1 scans, and resection cavities were contoured on MRI-2 and MRI-3 scans. RESULTS: The mean tumor volume before surgery was 14.23 cm3, and the mean cavity volume was 8.53 cm3 immediately after surgery and 8.77 cm3 before SRS. In the interval between surgery and SRS, 20 cavities (46.5%) were stable in size, defined as a change of ≤2 cm3; 10 cavities (23.3%) collapsed by >2 cm3; and 13 cavities (30.2%) increased by >2 cm3. The unexpected increase in cavity size was a result of local progression (2 cavities), accumulation of cyst-like fluid or blood (9 cavities), and nonspecific postsurgical changes (2 cavities). Finally, in the interval between surgery and SRS, 5 cavities showed definite local tumor progression, 4 patients had progression elsewhere in the brain, 1 patient had both local progression and progression elsewhere, and 33 patients had stable intracranial disease. CONCLUSIONS: In the interval between surgical resection and delivery of SRS, surgical cavities are dynamic in size; however, most cavities do not collapse, and nearly one-third are larger at the time of SRS. These observations support obtaining imaging for radiosurgery planning as close to SRS delivery as possible and suggest that delaying SRS after surgery does not offer the benefit of cavity collapse in most patients. A prospective, multi-institutional trial will provide more guidance to the optimal timing of cavity SRS.

Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker.

OBJECT: Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. METHODS: The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board-approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. RESULTS: A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. CONCLUSIONS: These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors.

Long-term response of pituitary carcinoma to temozolomide. Report of two cases.

Pituitary carcinoma is a rare tumor characterized by poor responsiveness to therapy, leading to early death. Reported responses to standard chemotherapy have only been anecdotal, with no single agent or combination demonstrating consistent efficacy in the treatment of patients with this disease. The authors report rare examples of a persistent response to cytotoxic chemotherapy in two patients with pituitary carcinoma. One patient was a 38-year-old man with visual field loss caused by a luteinizing hormone-secreting pituitary carcinoma that had recurred despite multiple surgeries and radiation therapy. Intradural metastases to the spine that had failed to respond to radiation therapy were pathologically confirmed. The second patient was a 26-year-old man with hyperprolactinemia from a prolactin-secreting pituitary tumor. Spine magnetic resonance images obtained to search for causes of neck pain showed a vertebral tumor, which was later confirmed through pathological analysis to be a metastatic pituitary carcinoma. His disease progressed despite radiation therapy, high-dose bromocriptine, and chemotherapy. Both patients were treated monthly with temozolomide, which was administered orally on the first 5 days of a 28-day cycle. The patient in the first case underwent all 12 treatment cycles without serious side effects, and his visual field deficits improved. The patient in the second case had undergone only 10 cycles when the drug was stopped because of his severe fatigue. Nonetheless, his pain disappeared and his serum prolactin concentration decreased. Both patients continue to have partial responses and have been employed full-time for more than 1 year after discontinuing temozolomide therapy. These two examples demonstrate that temozolomide may be effective in treating pituitary carcinomas and thus should be considered in the treatment algorithm for these difficult cases.