Preradiosurgical Embolization of Arteriovenous Malformations Reduces Target Volume - The Main Determinant for Complete Obliteration.

BACKGROUND: Embolization and stereotactic radiosurgery (SRS) have increasingly been used to treat complex arteriovenous malformations (AVMs). We studied outcomes of AVM patients treated through a multidisciplinary approach, examined the effect of embolization on SRS success, and analyzed predictors of treatment failure. METHODS: We retrospectively reviewed a prospectively maintained database of patients with AVMs treated with Gamma Knife (Leksell) SRS over an 11-year period. Patients with incomplete medical records and follow-up <2 years were excluded. Demographics, clinical presentation, previous rupture history, angiographic nidus size, Spetzler-Martin (S-M) grade, adjunctive endovascular embolization and microsurgical resection, radiologic evidence of obliteration and hemorrhage, and clinical outcomes (modified Rankin Scale [mRS] scores) were recorded. Radiosurgery-related details including nidus volume and number of sessions and radiosurgery-, embolization-, and resection-associated complications were also recorded. RESULTS: Eighty-three patients (mean age, 41.0 ± 21.3 years) were included. Mean reduction in AVM nidus target volume with endovascular embolization was 66.0 ± 19.7%. S-M grade reduction was achieved in 51.6% cases. Total obliteration after SRS was achieved in 56 AVMs (67.5%) after 2 years, and in 38 (86.4%) after 4 years. Two (2.4%) patients had rehemorrhage after SRS. Overall complication rate was 3.6%. Median angiographic follow-up was 55.5 months. Favorable outcomes (mRS = 0-2) were seen in 77.1%. SRS target volume was an independent predictor of treatment failure regardless of pre-SRS embolization. CONCLUSIONS: High AVM obliteration rates were achieved with judicious use of radiosurgery alone or with embolization. Embolization reduced target nidus volume by an average of 66%. SRS target volume was an independent predictor of treatment failure.

Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.

The following questions and recommendations are pertinent to the following: TARGET POPULATION: These recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation. QUESTION 1: In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: Level III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival. QUESTION 2: In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: Level III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity. QUESTION 3: In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 4: In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 5: In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 6: In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 7: In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question. QUESTION 8: In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival? RECOMMENDATION: There is insufficient evidence to support a recommendation regarding this question.

Radiographic pituitary stalk disruption: A rare sequela of secondary empty sella syndrome.

BACKGROUND: This two-patient case series describes a rare sequela of postoperative empty sella syndrome (ESS) following transsphenoidal resection of pituitary macroadenomas. This is characterized by progressive hormone dysfunction, diabetes insipidus (DI), and associated MRI evidence of pituitary stalk disruption. CASE DESCRIPTION: This phenomenon was retrospectively evaluated in a review of 2000 pituitary tumor resections performed by a single neurosurgeon (KOL). Chart review was retrospectively conducted to gather data on demographics, pituitary hormone status, tumor characteristics, and management. We identified 2 (0.1%) cases of progressive pituitary endocrine dysfunction occurring in the postoperative period associated with MRI evidence of pituitary stalk disruption within 6 weeks of discharge from the hospital. This was felt to be caused by the rapid descent of the residual normal pituitary gland down to the floor of the postoperative empty sella, causing relatively swift stalk stretching. Both patients developed DI, and one patient demonstrated increased pituitary hormone dysfunction. CONCLUSION: This phenomenon is a rare manifestation of postoperative ESS, secondary to surgical resection of a pituitary macroadenoma. We discuss the associated potential risk factors and strategies for avoidance in these two cases. Routine instillation of intrasellar fat in patients at risk is felt to be protective.

Evaluation of Benefit and Cost Utility of Immediate Postanesthesia Care Unit Radiographs to Predict Airway Compromise After Anterior Cervical Discectomy and Fusion.

STUDY DESIGN: Retrospective review. OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure that may be complicated by airway compromise postoperatively. This life-threatening complication may necessitate reintubation and reoperation. We evaluated the cost utility of conventional postoperative x-ray. SUMMARY OF BACKGROUND DATA: Studies have demonstrated minimal benefit in obtaining an x-ray on postoperative day 1, but there is some utility of postanesthesia care unit (PACU) x-rays for predicting the likelihood of reoperation. METHODS: We retrospectively reviewed the records of consecutive patients who underwent ACDF between September 2013 and February 2017. Patients were dichotomized into those who received PACU x-rays and those who did not (control group). Primary outcomes were reoperation, reintubation, mortality, and health care costs. RESULTS: Eight-hundred and fifteen patients were included in our analysis: 558 had PACU x-rays; 257 did not. In those who received PACU x-rays, mean age was 53.7 ±â€Š11.3 years, mean levels operated on were 2.0 ±â€Š0.79, and mean body mass index (BMI) was 30.3 ±â€Š6.9. In those who did not, mean age was 51.8 ±â€Š10.9 years, mean levels operated on were 1.48 ±â€Š0.65, and mean BMI was 29.9 ±â€Š6.3. Complications in the PACU x-ray group were reintubation-0.4%, reoperation-0.7%, and death-0.3% (due to prevertebral swelling causing airway compromise). Complications in the control group were reintubation-0.4%, reoperation-0.8%, and death-0. There were no differences between groups with respect to reoperation (P = 0.92), reintubation (P = 0.94), or mortality (P = 0.49). The mean per-patient cost was significantly higher (P = 0.009) in those who received PACU x-rays, $1031.76 ±â€Š948.67, versus those in the control group, $700.26 ±â€Š634.48. Mean length of stay was significantly longer in those who had PACU x-rays (P = 0.01). CONCLUSION: Although there were no differences in reoperation, reintubation, or mortality, there was a significantly higher cost for care and hospitalization in those who received PACU x-rays. Further studies are warranted to validate the results of the presented study.Level of Evidence: 3.

Endoscopic Carpal Tunnel Release.

Carpal tunnel syndrome represents compression of the median nerve in the carpal tunnel, which is defined by the carpal bones on the lateral, medial, and dorsal aspects and the transverse carpal ligament on the anterior aspect.1 Symptoms of carpal tunnel syndrome include paresthesia, anesthesia, paresis, and pain located in the median nerve distribution. In severe cases, there may be atrophy of median nerve-innervated thenar muscles. In the United States, carpal tunnel syndrome affects approximately 3.72% of the population.2 Conservative measures, such as bracing, steroid injections, and physical and occupational therapy, are commonly employed.1 However, many patients still require more definitive surgical management, which may be in the form of open or endoscopic procedures. Regardless of surgical approach, the clinical success rates of carpal tunnel release have been reported to be 75%-90%.3 Recurrence rates are 8.4%-15% over 4-5 years,4,5 with the lower end of this range representing the Agee single-portal technique. Endoscopic carpal tunnel release leads to reduced postoperative pain and an increase in transient neurologic deficits; however, no improvements have been reported in overall complication rate, subjective satisfaction, return to work, postoperative grip and pinch strength, and operative time.6 In this technical video, we present a case of single-incision endoscopic carpal tunnel release in a patient with severe symptoms after conservative measures failed. The patient experienced a noncomplicated postoperative course and demonstrated an excellent recovery at follow-up visits. Surgical decompression is an important treatment for refractory carpal tunnel syndrome, and videos such as this provide guidance for safe and effective treatment (Video 1).

The case for radiosurgery for brainstem metastases.

PURPOSE: To challenge the prevalent pessimism regarding the outcome of patients with metastases in the brainstem resulting in the use of whole brain radiation for palliation rather than stereotactic radiosurgery for definitive control and preservation of quality of life. We present our single institution review of the efficacy and safety of treating brainstem metastases aggressively with GKRS. METHODS: Forty-one patients with 45 total lesions treated with GKRS were included. Mean age was 58.7 years, ranging from 22 to 82. Tumor volumes were objectively calculated, treatment effects assessed on imaging and clinical data collected and correlated to the radiosurgical response. RESULTS: Mean survival after diagnosis of BSM was 11.6 months, ranging from 1.4 to 58.8 months. Margin dose ranged from 12 to 20 Gy. At first follow up, 11 (27%) patients had complete resolution of the treated lesion. At the second follow up 15 (37%) and third follow up 19 (46%) patients had a complete response. On average, there was a 64% decrease in tumor size at first follow up after treatment. 25 (61%) patients received WBRT in addition to radiosurgery; 16 (39%) received radiosurgery alone. There was no difference in overall survival between the two groups (p = 0.1324). ARE was seen in one patient who received  16 Gy to the margin of a 2.06 cm3 pontine tumor, but without correlative symptoms. One patient was treated with Bevacizumab® for progressive, but asymptomatic, edema following treatment that was not controlled by corticosteroids. CONCLUSIONS: Location in brainstem should not be a deterrent to the use of radiosurgery for these patients. The addition or exclusion of WBRT should be based on the clinical progression of the patient and within the limits of this study does not seem to impact overall survival. With improved survival as a result of better systemic therapy, these patients can benefit from better preservation of cognitive function by this strategy.

Cervical sagittal balance parameters after single-level anterior cervical discectomy and fusion: Correlations with clinical and functional outcomes.

BACKGROUND: Normal sagittal cervical alignment has been associated with improved outcome after anterior cervical discectomy and fusion (ACDF). OBJECTIVE: The aim of this study is to identify alterations of cervical sagittal balance parameters after single-level ACDF and assess correlations with postoperative functionality. METHODS: A retrospective chart review was performed between January 2010 and January 2014 to identify adult patients with no previous cervical spine surgery who underwent ACDF at any one level between C2 and C7 for the single-level degenerative disease. Tumor, infection, and trauma cases were excluded from the study. For the included cases, the following data were recorded preoperatively and 6 months-1 year after surgery: sagittal balance-marker measurements of the C1-C2 angle, C2-C7 angle, C7 slope, segmental angle at the operated level, and sagittal vertical axis (SVA) distance between C2 and C7, as well as the neck disability index and visual analog scale of pain. RESULTS: The present study included 47 patients (average age: 51.2 years; range: 28-86 years). A moderate negative correlation between a smaller C2-C7 angle and the presence of right arm pain before treatment was found (P = 0.0281). Postoperatively, functionality scores significantly improved in all patients. C1-C2 angle increased with statistical significance (P = 0.0255). C2-C7 angle, segmental angle, C7 slope, and SVA C2-C7 distance did not change with statistical significance after surgery. C7 slope significantly correlated with overall cervical sagittal balance (P < 0.05). CONCLUSIONS: Single-level ACDF significantly increases upper cervical lordosis (C1-C2) without significantly changing lower cervical lordosis (C2-C7). The C7 slope is a significant marker of overall cervical sagittal alignment (P < 0.05).

Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth In Vivo.

Purpose: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in many cancers and represents an attractive molecule for targeted cancer therapy. Although primarily regarded as an intracellular protein with diverse actions, survivin has also been identified in association with circulating tumor exosomes.Experimental Design: We have reported that active, specific vaccination with a long peptide survivin immunogen leads to the development of survivin-specific CD8-mediated tumor cell lysis and prolongation of survival in tumor-bearing mice. In addition to cellular antitumor responses, circulating anti-survivin antibodies are detected in the serum of mice and human glioblastoma patients following vaccination with the survivin immunogen.Results: Here we demonstrate that survivin is present on the outer cell membrane of a wide variety of cancer cell types, including both murine and human glioma cells. In addition, antibodies to survivin that are derived from the immunogen display antitumor activity against murine GL261 gliomas in both flank and intracranial tumor models and against B16 melanoma as well.Conclusions: In addition to immunogen-induced, CD8-mediated tumor cell lysis, antibodies to the survivin immunogen have antitumor activity in vivo Cell-surface survivin could provide a specific target for antibody-mediated tumor immunotherapeutic approaches. Clin Cancer Res; 24(11); 2642-52. ©2018 AACR.

Impact of the Number of Metastatic Tumors Treated by Stereotactic Radiosurgery on the Dose to Normal Brain: Implications for Brain Protection.

PURPOSE/OBJECTIVES: The purpose of this study was to evaluate the effect of the number of brain lesions for which stereotactic radiosurgery (SRS) was performed on the dose volume relationships in normal brain. MATERIALS AND METHODS: Brain tissue was segmented using the patient's pre-SRS MRI. For each plan, the following data points were recorded: total brain volume, number of lesions treated, volume of brain receiving 8 Gy (V8), V10, V12, and V15. RESULTS: A total of 225 Gamma Knife® treatments were included in this retrospective analysis. The number of lesions treated ranged from 1 to 29. The isodose for prescription ranged from 40 to 95% (mean 55%). The mean prescription dose to tumor edge was 18 Gy. The mean coverage, selectivity, conformity, and gradient index were 97.5%, 0.63, 0.56, and 3.5, respectively. The mean V12 was 9.5 cm3 (ranging from 0.5 to 59.29). There was no correlation between the number of lesions and brain V8, V12, V10, or V15. There was a direct and statistically significant relationship between the brain volume treated (V8, V10, V12, and V15) and total volume of tumors treated (p < 0.001). In our study, the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3. CONCLUSIONS: The number of metastatic brain lesions treated bears no significant relationship to total brain tissue volume treated when using SRS. The fact that the integral dose to the brain exceeded 3 J when the total tumor volume exceeded 25 cm3 is useful for establishing guidelines. Although standard practice has favored using whole brain radiation therapy in patients with more than 4 lesions, a significant amount of normal brain tissue may be spared by treating these patients with SRS. SRS should be carefully considered in patients with multiple brain lesions, with the emphasis on total brain volume involved rather than the number of lesions to be treated.

Novel vaccines for glioblastoma: clinical update and perspective.

Glioblastoma is the most common primary brain cancer. Aggressive treatment with surgery, radiation therapy and chemotherapy provides limited overall survival benefit. Glioblastomas have a formidable tumor microenvironment that is hostile to immunological effector cells and these cancers produce profound systemic immunosuppression. However, surgical resection of these tumors creates conditions that favor the use of immunotherapeutic strategies. Therefore, extensive surgical resection, when feasible, will remain part of the equation to provide an environment in which active specific immunotherapy has the greatest chance of working. Toward that end, a number of vaccination protocols are under investigation. Vaccines studied to date have produced cellular and humoral antitumor responses, but unequivocal clinical efficacy has yet to be demonstrated. In addition, focus is shifting toward the prospect of therapies involving vaccines in combination with immune checkpoint inhibitors and other immunomodulatory agents so that effector cells remain active against their targets systemically and within the tumor microenvironment.

Perioperative complications after neoadjuvant chemotherapy with and without bevacizumab for colorectal liver metastases.

PURPOSE: Bevacizumab has been shown to increase progression free and overall survival in patients with metastatic colorectal cancer. Neoadjuvant bevacizumab is commonly used in patients undergoing liver resection. Our purpose was to evaluate whether bevacizumab is associated with increased rate of perioperative complications in patients undergoing hepatic resection for colorectal liver metastases (CRLM). METHODS: Retrospective analysis of patients undergoing hepatic resection for CRLM who received chemotherapy and bevacizumab (group 1, n = 134), or chemotherapy alone (group 2, n = 57). We compared demographics, surgical characteristics, and perioperative course. RESULTS: Perioperative complications developed in 35 % of patients in group 1, and 47 % in group 2 (p = 0.11). Of those complications, 15 (11.2 %) in group 1, and 5 (8.8 %) in group 2 were considered major (p = 0.617). Four patients, all of whom received preoperative bevacizumab, developed enteric leaks following combined liver and bowel resection. The rate of anastomotic leak in group 1 was 10 %, compared with 0 in group 2, p = 0.56. CONCLUSION: Neoadjuvant chemotherapy along with bevacizumab was not associated with an increased risk of postoperative complications after hepatic resection. Possible association of increased morbidity with simultaneous bowel and liver resections following bevacizumab administration was found and we recommend avoiding such treatment combination.