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Item Adenoid Cystic Carcinoma (ACC) Infiltrating the Skull Base: A Systematic Review of Clinical Characteristics and Management Strategies(International Institute of Anticancer Research, 2022-09-03) Bin-Alamer, Othman; Haider, Ali S.; Chaudhary, Adhiraj; Balasubramanian, Kishore; Breeding, Tessa; Palmisciano, Paolo; Haider, Maryam; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Yu, Kenny; Neurological Surgery, School of MedicineBackground/aim: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. Materials and methods: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. Results: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. Conclusion: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.Item Adenoid Cystic Carcinoma (ACC) Infiltrating the Skull Base: A Systematic Review of Clinical Characteristics and Management Strategies(IIAR, 2022-09-03) Bin-Alamer, Othman; Haider, Ali S.; Chaudhary, Adhiraj; Balasubramanian, Kishore; Breeding, Tessa; Palmisciano, Paolo; Haider, Maryam; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Yu, Kenny; Neurological Surgery, School of MedicineBackground/Aim: To systematically review the patient characteristics and management approaches of adenoid cystic carcinoma (ACC) infiltrating the skull base. Materials and Methods: According to PRISMA guidelines, PubMed, Scopus, and Cochrane were searched to retrieve studies reporting management protocols and survival outcomes of patients with skull base ACCs. Patient characteristics, management strategies, and outcomes were investigated. Results: The review encompassed 17 studies involving 171 patients, with a female predominance (57.9%) and a mean age of 49±7.12 years. ACCs mostly infiltrated the paranasal sinus (22.2%), cavernous sinus (8.8%), and nasopharynx (7.1%). Perineural invasion was reported in 6.4% of cases. Facial pain, nasal obstruction, and facial paresthesia were the most common symptoms. Surgical resection (45.6%) was favored over biopsy (12.2%). Employing the free flap technique (4.7%), surgical reconstruction of the bony defect after resection was performed using abdominal and anterior thigh muscle grafts in 1.8% of patients each. As adjuvant management, 22.8% of cases had radiotherapy and 14.6% received chemotherapy. Recurrence of skull base ACCs occurred in 26.9% of cases during a mean follow up-time of 30.8±1.8 months. Conclusion: Skull base ACCs pose a surgical challenge mainly due to their proximity to critical neurovascular structures and aggressive behavior. Surgical resection and radiotherapy are shown to be safe and effective treatment modalities. The dismal prognosis and limited data on non-surgical strategies highlight the need for further evaluation of the current management paradigm and upraising innovative therapies to improve patient mortality and quality of life.Item Comparison of Blister Aneurysm Treatment Techniques: A Systematic Review and Meta-Analysis(Elsevier, 2021-10) Sanchez, Victoria E.; Haider, Ali S.; Rowe, Scott E.; Wahood, Waseem; Sagoo, Navraj S.; Ozair, Ahmad; El Ahmadieh, Tarek Y.; Kan, Peter; Johnson, Jeremiah N.; Neurological Surgery, School of MedicineObjective Blood blister aneurysms are small, thin-walled, rapidly growing side-wall aneurysms that have proven particularly difficult to treat, and evidence-based guidance for treatment strategies is lacking. A systematic review and meta-analysis was performed to aggregate the available data and compare the three primary treatment modalities. Methods We performed a comprehensive literature search according to PRISMA guidelines followed by an indirect meta-analysis that compares the safety and efficacy of surgical, flow-diverting stents (FDS), and other endovascular approaches for the treatment of ruptured blood blister aneurysms. Results A total of 102 studies were included for quantitative synthesis with sample sizes of 687 treated surgically, 704 treated endovascularly without FDS, and 125 treated via flow-diversion. Comparatively, FDS achieved significantly reduced rates of perioperative retreatment compared to both surgical (P=0.025) and non-FDS endovascular (P<0.001). The FDS subgroup also achieved a significantly lower incidence of perioperative rebleed (P<0.001), perioperative hydrocephalus (P=0.012), postoperative infarction (P=0.002), postoperative hydrocephalus (P<0.001), and postoperative vasospasm (P=0.002) when compared to those patients in the open surgical subgroup. While no significant differences were found between groups on the basis of functional outcomes, angiographic outcomes detailed by rates of radiographic complete occlusion were highest for surgical (90.7%, 262/289) and FDS (89.1%, 98/110) subgroups versus the non-FDS endovascular subgroup at (82.7%, 268/324). Conclusion Flow-diversion appears to be an effective treatment strategy for ruptured BBAs with lower rates of perioperative complications when compared to surgical and other endovascular techniques but studies investigating long-term outcomes following flow-diversion warrant further study.Item Craniopharyngiomas Invading the Ventricular System: A Systematic Review(International Institute of Anticancer Research, 2022) Palmisciano, Paolo; Young, Kurtis; Ogasawara, Maya; Yousefi, Omid; Ogasawara, Christian; Ferini, Gianluca; Bin-Alamer, Othman; Sharma, Mayur; Umana, Giuseppe E.; Yu, Kenny; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Haider, Ali S.; Neurological Surgery, School of MedicineBackground/aim: Craniopharyngiomas involving the ventricular system are rare but pose significant surgical challenges. We systematically reviewed the literature on craniopharyngiomas invading the ventricles (CP-V). Materials and methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched to include studies reporting clinical data of patients with CP-Vs. Clinico-radiological features, management, and treatment outcomes were analyzed. Results: We included 73 studies encompassing 407 patients. Patients were mostly male (61.5%), presenting with headache (57.9%) and/or endocrine disorders (52.1%). CP-Vs mostly involved the third ventricle (96.3%), followed by the lateral ventricles (2.9%), and the fourth ventricle (1%). Tumors had cystic components in 59% of cases and were mostly adamantinomatous (70.8%). Open resection was performed in 232 cases (57%), mostly with trans-lamina terminalis (36.6%) and trans-callosal (31.9%) approaches. Endoscopic resection was performed in 169 cases (41.5%), mostly with trans-sphenoidal (74.6%) and transventricular (24.9%) approaches. Gross-total tumor resection was obtained in most cases (62.9%). Adjuvant radiotherapy was delivered in 22.8% cases. A total of 178 patients experienced persistent complications, mostly including diabetes insipidus (47.1%) and panhypopituitarism (12.7%), not significantly different after open versus endoscopic resection (p=0.117). Symptom improvement was obtained in 88% of cases. CP-Vs recurrences were reported in 94 patients (23.1%), with median progression-free survival of 13.5 months (range=0.5-252.0 months). Fifty-nine patients died (14.5%), with median overall survival of 32.0 months (range=0.5-252.0 months), significantly longer after endoscopic resection than open resection (p=0.019). Conclusion: CP-Vs are uncommon and challenging entities. Surgical resection is feasible, but patient-tailored selection of open/endoscopic approaches is necessary to achieve optimal outcomes and minimize complication risks.Item Gliomas Infiltrating the Corpus Callosum: A Systematic Review of the Literature(MDPI, 2022-05-19) Palmisciano, Paolo; Ferini, Gianluca; Watanabe, Gina; Ogasawara, Christian; Lesha, Emal; Bin-Alamer, Othman; Umana, Giuseppe E.; Yu, Kenny; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Haider, Ali S.; Neurological Surgery, School of MedicineBackground: Gliomas infiltrating the corpus callosum (G-I-CC) majorly impact patient quality-of-life, but maximally safe tumor resection is challenging. We systematically reviewed the literature on G-I-CC. Methods: PubMed, EMBASE, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies of patients with G-I-CC. Clinicopathological features, treatments, and outcomes were analyzed. Results: We included 52 studies comprising 683 patients. Most patients experienced headache (33%), cognitive decline (18.7%), and seizures (17.7%). Tumors mostly infiltrated the corpus callosum genu (44.2%) with bilateral extension (85.4%) into frontal (68.3%) or parietal (8.9%) lobes. Most G-I-CC were glioblastomas (84.5%) with IDH-wildtype (84.9%) and unmethylated MGMT promoter (53.5%). Resection (76.7%) was preferred over biopsy (23.3%), mostly gross-total (33.8%) and subtotal (32.5%). The tumor-infiltrated corpus callosum was resected in 57.8% of cases. Radiation was delivered in 65.8% of patients and temozolomide in 68.3%. Median follow-up was 12 months (range, 0.1−116). In total, 142 patients (31.8%) experienced post-surgical complications, including transient supplementary motor area syndrome (5.1%) and persistent motor deficits (4.3%) or abulia (2.5%). Post-treatment symptom improvement was reported in 42.9% of patients. No differences in rates of complications (p = 0.231) and symptom improvement (p = 0.375) were found in cases with resected versus preserved corpus callosum. Recurrences occurred in 40.9% of cases, with median progression-free survival of 9 months (0.1−72). Median overall survival was 10.7 months (range, 0.1−116), significantly longer in low-grade tumors (p = 0.013) and after resection (p < 0.001), especially gross-total (p = 0.041) in patients with high-grade tumors. Conclusions: G-I-CC show clinicopathological patterns comparable to other more frequent gliomas. Maximally safe resection significantly improves survival with low rates of persistent complications.Item LMD-10. The role of immune checkpoint inhibitors in leptomeningeal disease: a systematic review(Oxford University Press, 2021-08) Palmisciano, Paolo; Haider, Ali S.; Nwagwu, Chibueze D.; Wahood, Waseem; Sagoo, Navraj S.; Yu, Kenny; Ene, Chibawane I.; O’Brien, Barbara J.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Neurological Surgery, School of MedicineBackground: Leptomeningeal disease (LMD) is a devastating complication of advanced malignancy with a poor prognosis and limited therapeutic options. Whether immune checkpoint inhibitors (ICIs) alter disease course is unknown. Methods: We searched PubMed, EMBASE, Scopus, Cochrane, and clinicaltrials.gov according to PRISMA guidelines to analyze the therapeutic role and toxicity profiles of ICIs in the management of LMD. Studies reporting clinical outcome data of patients with LMD treated with ICIs were included. A comprehensive review of clinical characteristics and survival analysis was conducted. Results: We included 14 studies encompassing 61 patients. The median age at LMD diagnosis was 57 years (female=63.9%). Lung cancer (44.3%), breast cancer (27.9%), and melanoma (23.0%) were the most frequent primary tumors. Parenchymal brain metastases occurred in 37 patients, mostly treated with radiotherapy (83.3%). LMD most frequently presented with headache (42.1%) and was diagnosed by MRI findings (leptomeningeal T1-contrast enhancement: 96.7%) and/or positive cerebrospinal fluid cytology (86.5%). Patients received ICIs for a median duration of 7 months (range, 0.5–58.0): pembrolizumab (49.2%), nivolumab (32.8%), and/or ipilimumab (18.0%). The most common concurrent LMD treatments were radiotherapy (54.7%) and steroids (35.7%). Radiological responses at 6-months were complete (33.3%) and partial response (12.5%), stable disease (33.3%), and progression (20.8%). 22 patients developed ICI-related adverse events, mostly mild (100%) and uncommonly severe (15.6%). Median progression-free survival was 5.1 months, median overall survival was 6.3 months, and 12-month survival was 32.1%. Survival was correlated with ICIs (P=0.042), but not with primary tumors (P=0.144). Patients concurrently receiving steroids showed worse survival (P=0.040), with a median overall survival of 1.9 months. Conclusion: ICI therapy shows promise and appears to be well-tolerated in patients with LMD. Concurrent use of steroids is associated with worse survival. The role of ICIs in the multimodal management of LMD and their combination with steroids requires further analysis.Item Metastases in the Pineal Region: A Systematic Review of Clinical Features, Management Strategies, and Survival Outcomes(Elsevier, 2022) Palmisciano, Paolo; Ogasawara, Christian; Nwagwu, Chibueze D.; Bin Alamer, Othman; Gupta, Aditya D.; Giantini-Larsen, Alexandra M.; Scalia, Gianluca; Yu, Kenny; Umana, Giuseppe E.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Haider, Ali S.; Neurological Surgery, School of MedicineBackground: Pineal region metastases are rare but often cause severe neurologic deficits. Surgical resection and chemoradiotherapy can provide therapeutic benefit. We investigated the literature to analyze clinical characteristics, management strategies, and survival of adult patients with pineal region metastases. Methods: PubMed, Embase, Scopus, and Cochrane were searched following the PRISMA guidelines, including studies reporting clinical outcomes of patients with pineal region metastases. Clinical presentation, management, and survival were reviewed. Results: We included 31 studies comprising 47 patients. Lung cancer (29.8%) and carcinomas of unknown origin (14.9%) were the most frequent primary tumors. In 48.9% of patients, symptomatic pineal metastases preceded primary tumor diagnosis. Headache (67.4%) and confusion (46.5%) were the most common symptoms. Parinaud syndrome (46.5%) and hydrocephalus (87.2%) were noted. Biopsy (65.9%) was preferred over resection (34.1%), and shunting strategies used were endoscopic third ventriculostomy (43.9%) and ventriculoperitoneal (26.8%). Eleven patients (32.3%) received adjuvant chemotherapy and 32 (68%) received radiotherapy. Posttreatment improvement in symptoms (56.6%) and hydrocephalus (80.5%) were noted. In patients who received adjuvant chemotherapy/radiotherapy, significant improvement in posttreatment performance status occurred with both biopsy (P < 0.001) and resection (P = 0.007). No survival differences were reported between surgery and biopsy (P = 0.912) or between complete and partial resection (P = 0.220). Overall survival was neither influenced by surgical approach (P = 0.157) nor by shunting strategy (P = 0.822). Mean follow-up was 8 months and median overall survival 3 months. Only 2 cases (4.8%) of pineal metastasis showed recurrence. Conclusions: Pineal region metastases carry significant morbidity. Biopsy or surgical resection, combined with adjuvant chemotherapy/radiotherapy and/or shunting, may significantly improve performance status.Item Neoadjuvant Stereotactic Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis of the Literature and Ongoing Clinical Trials(MDPI, 2022-09-04) Palmisciano, Paolo; Ferini, Gianluca; Khan, Ramlah; Bin-Alamer, Othman; Umana, Giuseppe E.; Yu, Kenny; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Haider, Ali S.; Neurological Surgery, School of MedicineBackground: Brain metastases (BMs) carry a high morbidity and mortality burden. Neoadjuvant stereotactic radiotherapy (NaSRT) has shown promising results. We systematically reviewed the literature on NaSRT for BMs. Methods: PubMed, EMBASE, Scopus, Web-of-Science, Cochrane, and ClinicalTrial.gov were searched following the PRISMA guidelines to include studies and ongoing trials reporting NaSRT for BMs. Indications, protocols, and outcomes were analyzed using indirect random-effect meta-analyses. Results: We included 7 studies comprising 460 patients with 483 BMs, and 13 ongoing trials. Most BMs originated from non-small lung cell carcinoma (41.4%), breast cancer (18.7%) and melanoma (43.6%). Most patients had single-BM (69.8%) located supratentorial (77.8%). Patients were eligible if they had histologically-proven primary tumors and ≤4 synchronous BMs candidate for non-urgent surgery and radiation. Patients with primary tumors clinically responsive to radiotherapy, prior brain radiation, and leptomeningeal metastases were deemed non-eligible. Median planning target volume was 9.9 cm3 (range, 2.9-57.1), and NaSRT was delivered in 1-fraction (90.9%), 5-fraction (4.8%), or 3-fraction (4.3%), with a median biological effective dose of 39.6 Gy10 (range, 35.7-60). Most patients received piecemeal (76.3%) and gross-total (94%) resection after a median of 1-day (range, 1-10) post-NaSRT. Median follow-up was 19.2-months (range, 1-41.3). Actuarial post-treatment rates were 4% (95%CI: 2-6%) for symptomatic radiation necrosis, 15% (95%CI: 12-18%) and 47% (95%CI: 42-52%) for local and distant recurrences, 6% (95%CI: 3-8%) for leptomeningeal metastases, 81% (95%CI: 75-87%) and 59% (95%CI: 54-63%) for 1-year local tumor control and overall survival. Conclusion: NaSRT is effective and safe for BMs. Ongoing trials will provide high-level evidence on long-term post-treatment outcomes, further compared to adjuvant stereotactic radiotherapy.Item Orbital Exenteration for Craniofacial Lesions: A Systematic Review and Meta-Analysis of Patient Characteristics and Survival Outcomes(MDPI, 2023-08-27) Qedair, Jumanah; Haider, Ali S.; Balasubramanian, Kishore; Palmisciano, Paolo; Hassan, Taimur; Shahbandi, Ataollah; Sabahi, Mohammadmahdi; Kharbat, Abdurrahman F.; Abou-Al-Shaar, Hussam; Yu, Kenny; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Bin-Alamer, Othman; Neurological Surgery, School of MedicineBackground: The outcomes of orbital exenteration (OE) in patients with craniofacial lesions (CFLs) remain unclear. The present review summarizes the available literature on the clinical outcomes of OE, including surgical outcomes and overall survival (OS). Methods: Relevant articles were retrieved from Medline, Scopus, and Cochrane according to PRISMA guidelines. A systematic review and meta-analysis were conducted on the clinical characteristics, management, and outcomes. Results: A total of 33 articles containing 957 patients who underwent OE for CFLs were included (weighted mean age: 64.3 years [95% CI: 59.9-68.7]; 58.3% were male). The most common lesion was squamous cell carcinoma (31.8%), and the most common symptom was disturbed vision/reduced visual acuity (22.5%). Of the patients, 302 (31.6%) had total OE, 248 (26.0%) had extended OE, and 87 (9.0%) had subtotal OE. Free flaps (33.3%), endosseous implants (22.8%), and split-thickness skin grafts (17.2%) were the most used reconstructive methods. Sino-orbital or sino-nasal fistula (22.6%), flap or graft failure (16.9%), and hyperostosis (13%) were the most reported complications. Regarding tumor recurrences, 38.6% were local, 32.3% were distant, and 6.7% were regional. The perineural invasion rate was 17.4%, while the lymphovascular invasion rate was 5.0%. Over a weighted mean follow-up period of 23.6 months (95% CI: 13.8-33.4), a weighted overall mortality rate of 39% (95% CI: 28-50%) was observed. The 5-year OS rate was 50% (median: 61 months [95% CI: 46-83]). The OS multivariable analysis did not show any significant findings. Conclusions: Although OE is a disfiguring procedure with devastating outcomes, it is a viable option for carefully selected patients with advanced CFLs. A patient-tailored approach based on tumor pathology, extension, and overall patient condition is warranted.Item Orbital Metastases: A Systematic Review of Clinical Characteristics, Management Strategies, and Treatment Outcomes(MDPI, 2021-12-24) Palmisciano, Paolo; Ferini, Gianluca; Ogasawara, Christian; Wahood, Waseem; Alamer, Othman Bin; Gupta, Aditya D.; Scalia, Gianluca; Larsen, Alexandra M.G.; Yu, Kenny; Umana, Giuseppe E.; Cohen-Gadol, Aaron A.; El Ahmadieh, Tarek Y.; Haider, Ali S.; Neurological Surgery, School of MedicineBackground: Orbital metastases often lead to severe functional impairment. The role of resection, orbital exenteration, and complementary treatments is still debated. We systematically reviewed the literature on orbital metastases. Methods: PubMed, Scopus, Web-of-Science, and Cochrane were searched upon PRISMA guidelines to identify studies on orbital metastases. Clinical characteristics, management strategies, and survival were analyzed. Results: We included 262 studies comprising 873 patients. Median age was 59 years. The most frequent primary tumors were breast (36.3%), melanoma (10.1%), and prostate (8.5%) cancers, with median time interval of 12 months (range, 0-420). The most common symptoms were proptosis (52.3%) and relative-afferent-pupillary-defect (38.7%). Most metastases showed a diffuse location within the orbit (19%), with preferential infiltration of orbital soft tissues (40.2%). In 47 cases (5.4%), tumors extended intracranially. Incisional biopsy (63.7%) was preferred over fine-needle aspiration (10.2%), with partial resection (16.6%) preferred over complete (9.5%). Orbital exenteration was pursued in 26 patients (3%). A total of 305 patients (39.4%) received chemotherapy, and 506 (58%) received orbital radiotherapy. Post-treatment symptom improvement was significantly superior after resection (p = 0.005) and orbital radiotherapy (p = 0.032). Mean follow-up was 14.3 months, and median overall survival was 6 months. Fifteen cases (1.7%) demonstrated recurrence with median local control of six months. Overall survival was statistically increased in patients with breast cancer (p < 0.001) and in patients undergoing resection (p = 0.024) but was not correlated with orbital location (p = 0.174), intracranial extension (p = 0.073), biopsy approach (p = 0.344), extent-of-resection (p = 0.429), or orbital exenteration (p = 0.153). Conclusions: Orbital metastases severely impair patient quality of life. Surgical resection safely provides symptom and survival benefit compared to biopsy, while orbital radiotherapy significantly improves symptoms compared to not receiving radiotherapy.