Prognostic value of the Simpson grading scale in modern meningioma surgery: Barrow Neurological Institute experience.

OBJECTIVE: Recently, the prognostic value of the Simpson resection grading scale has been called into question for modern meningioma surgery. In this study, the authors analyzed the relationship between Simpson resection grade and meningioma recurrence in their institutional experience. METHODS: This study is a retrospective review of all patients who underwent resection of a WHO grade I intracranial meningioma at the authors' institution from 2007 to 2017. Binary logistic regression analysis was used to assess for predictors of Simpson grade IV resection and postoperative neurological morbidity. Cox multivariate analysis was used to assess for predictors of tumor recurrence. Kaplan-Meier analysis and log-rank tests were used to assess and compare recurrence-free survival (RFS) of Simpson resection grades, respectively. RESULTS: A total of 492 patients with evaluable data were included for analysis, including 394 women (80.1%) and 98 men (19.9%) with a mean (SD) age of 58.7 (12.8) years. The tumors were most commonly located at the skull base (n = 302; 61.4%) or the convexity/parasagittal region (n = 139; 28.3%). The median (IQR) tumor volume was 6.8 (14.3) cm3. Simpson grade I, II, III, or IV resection was achieved in 105 (21.3%), 155 (31.5%), 52 (10.6%), and 180 (36.6%) patients, respectively. Sixty-three of 180 patients (35.0%) with Simpson grade IV resection were treated with adjuvant radiosurgery. In the multivariate analysis, increasing largest tumor dimension (p < 0.01) and sinus invasion (p < 0.01) predicted Simpson grade IV resection, whereas skull base location predicted neurological morbidity (p = 0.02). Tumor recurrence occurred in 63 patients (12.8%) at a median (IQR) of 36 (40.3) months from surgery. Simpson grade I resection resulted in superior RFS compared with Simpson grade II resection (p = 0.02), Simpson grade III resection (p = 0.01), and Simpson grade IV resection with adjuvant radiosurgery (p = 0.01) or without adjuvant radiosurgery (p < 0.01). In the multivariate analysis, Simpson grade I resection was independently associated with no tumor recurrence (p = 0.04). Simpson grade II and III resections resulted in superior RFS compared with Simpson grade IV resection without adjuvant radiosurgery (p < 0.01) but similar RFS compared with Simpson grade IV resection with adjuvant radiosurgery (p = 0.82). Simpson grade IV resection with adjuvant radiosurgery resulted in superior RFS compared with Simpson grade IV resection without adjuvant radiosurgery (p < 0.01). CONCLUSIONS: The Simpson resection grading scale continues to hold substantial prognostic value in the modern neurosurgical era. When feasible, Simpson grade I resection should remain the goal of intracranial meningioma surgery. Simpson grade IV resection with adjuvant radiosurgery resulted in similar RFS compared with Simpson grade II and III resections.

Endonasal endoscopic resection of olfactory neuroblastoma: an 11-year experience.

OBJECTIVE: Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal cavity. Surgery has been and remains a mainstay of treatment for patients with this tumor. Open craniofacial resections have been the treatment of choice for many decades. More recently, experience has been growing with endoscopic approaches in the management of patients with ONB. The object of this study is to report the authors' experience over the past 11 years with ONB patients treated with purely endonasal endoscopic techniques. METHODS: The authors performed a retrospective chart review of 20 consecutive patients with ONB who underwent a completely endonasal endoscopic approach for an oncological tumor resection at their institution between January 2006 and January 2017. Patient demographics, tumor stage, pathological grade, frozen section analysis, permanent margin assessment, perioperative complications, postoperative therapy, length of follow-up, and outcomes at last follow-up were collected and analyzed. RESULTS: Eighteen patients presented with newly diagnosed disease, with a modified Kadish stage of A in 2 cases, B in 3, C in 11, and D in 2. Two patients presented with recurrent tumors. An average of 25.3 specimens per patient were examined by frozen section analysis. Although analysis of intraoperative frozen section margins was negative in all but 1 case, microscopic foci of tumor were found in 7 cases (35%) on permanent histopathological analysis. Perioperative complications occurred in 7 patients (35%) including 1 patient who developed a cerebrospinal fluid leak; there were no episodes of meningitis. All but 1 patient received postoperative radiotherapy, and 5 patients received postoperative chemotherapy. With a mean follow-up of over 5 years, 19 patients were alive and 1 patient died from an unrelated cause. There were 2 cases of tumor recurrence. The 5-year overall, disease-specific, and recurrence-free survival rates were 92.9%, 100%, and 92.9%, respectively. CONCLUSIONS: The current results provide additional evidence for the continued use of endoscopic procedures in the management of this malignancy.

Relevance of Simpson grading system and recurrence-free survival after surgery for World Health Organization Grade I meningioma.

OBJECTIVE The clinical significance of the Simpson system for grading the extent of meningioma resection and its role as a predictor of the recurrence of World Health Organization (WHO) Grade I meningiomas have been questioned in the past, echoing changes in meningioma surgery over the years. The authors reviewed their experience in resecting WHO Grade I meningiomas and assessed the association between extent of resection, as evaluated using the Simpson classification, and recurrence-free survival (RFS) of patients after meningioma surgery. METHODS Clinical and radiological information for patients with WHO Grade I meningiomas who had undergone resective surgery over the past 20 years was retrospectively reviewed. Simpson and Shinshu grading scales were used to evaluate the extent of resection. Statistical analysis was conducted using Kaplan-Meier curves and Cox proportional-hazards regression. RESULTS Four hundred fifty-eight patients were eligible for analysis. Overall tumor recurrence rates for Simpson resection Grades I, II, III, and IV were 5%, 22%, 31%, and 35%, respectively. After Cox regression analysis, Simpson Grade I (extensive resection) was revealed as a significant predictor of RFS (p = 0.003). Patients undergoing Simpson Grade I and II resections showed significant improvement in RFS compared with patients undergoing Grade III and IV resections (p = 0.005). Extent of resection had a significant effect on recurrence rates for both skull base (p = 0.047) and convexity (p = 0.012) meningiomas. Female sex and a Karnofsky Performance Scale score > 70 were also identified as independent predictors of RFS after resection of WHO Grade I meningioma. CONCLUSIONS In this patient cohort, a significant association was noted between extent of resection and rates of tumor recurrence. In the authors' experience the Simpson grading system maintains its relevance and prognostic value and can serve an important role for patient education. Even though complete tumor resection is the goal, surgery should be tailored to each patient according to the risks and surgical morbidity.

Long-term administration of bisphosphonate to reduce local recurrence of sacral giant cell tumor after nerve-sparing surgery.

OBJECTIVE The objective of this study was to investigate the effect of long-term bisphosphonate treatment on reducing local recurrence of sacral giant cell tumors (GCTs) after nerve-sparing surgery. METHODS Thirty-five consecutive patients with sacral GCTs who received treatment in Shanghai Changzheng Hospital between January 2000 and December 2010 were included in this study. Between January 2007 and December 2010, 19 patients received bisphosphonates following nerve-sparing surgery. Before January 2007, 16 patients received nerve-sparing surgery alone, and these cases were included as the control group. The difference in clinical data between the groups was compared by Student's t-test and 2-tailed chi-square or Fisher's exact test. The postoperative recurrence-free survival (RFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method and compared between the groups by log-rank test. A p value < 0.05 was considered statistically significant. RESULTS All of the patients had relatively good nerve function. The clinical data were homogeneous between the groups. The local recurrence rate was 10.53% (2 of 19) in the bisphosphonate treatment group and 43.75% (7 of 16) in the control group. The log-rank test showed that the 3-year RFS and 3-year OS in the bisphosphonate treatment group were significantly higher than those in the control group (RFS 89.5% vs 56.3%, p = 0.04; OS 100% vs 81.3%, p = 0.05). CONCLUSIONS The long-term use of bisphosphonates after nerve-sparing surgery is a viable option for the treatment of sacral GCTs. This approach could reduce local recurrences while preserving nerve function.

Characteristics of Rathke's cleft cyst based on cyst location with a primary focus on recurrence after resection.

OBJECT: Rathke's cleft cysts (RCCs) are benign lesions with a location that is entirely intrasellar, intrasellar with suprasellar extension (intrasuprasellar), or purely suprasellar. The recurrence of RCC is relatively uncommon. The present study was conducted to report clinical characteristics, histological features, and outcomes based on location of the cyst with a primary focus on analyzing the predictors of squamous metaplasia and recurrence in these 3 types of RCCs. METHODS: A retrospective review of the medical records of patients with symptomatic RCCs who had undergone resection at the authors' institution was conducted. Data points, including clinical presentation, preoperative endocrine status, operative details, imaging findings, pathology, and clinical outcomes, were reviewed. A multivariable regression model was used to identify predictors of recurrence. RESULTS: The mean age of the 87 eligible patients, 64 females and 23 males, was 41 ± 14 years (range 10-73 years). Sixteen patients (18%) had an entirely intrasellar RCC, 21 (24%) had a purely suprasellar cyst, and 50 (58%) had an intrasuprasellar RCC. The mean cyst volume was 2.4 ± 0.9 cm(3) (range 0.36-4.9 cm(3)). Headache was the most frequent initial symptom (76%) followed by visual disturbance (45%). The transsphenoidal approach was performed for all intrasellar RCCs (16 cysts) and 33 of 50 intrasuprasellar RCCs. The transcranial route was used for all suprasellar cysts (21 cysts) and 17 of 50 intrasuprasellar RCCs. Squamous metaplasia was present in 27 (31%) of 87 RCCs. The occurrence of squamous metaplasia was associated with cyst location (p = 0.027), T1 signal intensity (p = 0.004) and ring enhancement on Gd-enhanced MRI (p = 0.017), and cyst volume (p = 0.045). A suprasellar location (p = 0.048, OR 3.89, 95% CI 1.010-15.020), ring enhancement on Gd-enhanced MRI (p = 0.028, OR 3.922, 95% CI 1.158-13.288), hypointensity on T1-weighted MRI (p = 0.002, OR 6.86, 95% CI 1.972-23.909), and cyst volume (p = 0.01, OR 0.367, 95% CI 0.170-0.789) were independent predictors of squamous metaplasia. The mean time to reaccumulation (11 [12.6%] of 87 cases) and recurrence (7 [8%] of 87 cases) was 14 ± 6 months. Recurrence-free survival was 84.5% at a mean of 98.2 ± 4.6 months after treatment. A suprasellar cyst location (p = 0.007, OR 7.7, 95% CI 1.75-34.54), the occurrence of squamous metaplasia (p = 0.007, OR 19.3, 95% CI 2.25-165.18), and isointensity on T2-weighted MRI (p = 0.041, OR 10.29, 95% CI 1.094-96.872) were the independent predictors of RCC recurrence. CONCLUSIONS: A suprasellar cyst location, the occurrence of squamous metaplasia, and isointensity on T2-weighted MRI were independent predictors of RCC recurrence. The extent of resection and type of surgical approach used were not associated with recurrence. A tailored extent of resection based on cyst location and predictive factors is recommended.

Extended orbital exenteration for sinonasal malignancy with orbital apex extension: surgical technique and clinical analysis.

OBJECT: The majority of sinonasal malignancies present with advanced disease, and cure rates are generally poor. Surgical extirpation remains the mainstay of treatment. In cases of sinonasal malignancy with orbital apex extension, gross-total tumor resection requires orbital exenteration and bony skull base resection around the orbital apex to provide sufficient margins. In this retrospective study, the authors describe their surgical strategy in and technique for orbital exenteration with orbital apex resection in patients at Tokyo Medical and Dental University who had sinonasal malignancy with orbital apex extension. They also analyzed the clinical features of and the results in these patients. METHODS: Between February 2001 and August 2012 at the authors' institution, sinonasal malignancy with orbital apex extension was treated using craniofacial tumor resection with orbital exenteration including skull base bone around the orbital apex. The authors describe this technique and analyze the surgical indications, extent of resection, primary tumor location, outcome, pathological findings, and neoadjuvant and adjuvant therapies of the patients who underwent the technique. RESULTS: The patients consisted of 12 men and 3 women with a mean age of 47.7 years (range 14-79 years). The longest postoperative follow-up was 9.5 years, and the shortest was 0.67 year (mean 3.0 years). Tumor originated at the ethmoid sinus in 6 patients (40%), maxillary sinus in 5 (33%), nasal cavity in 2 (13%), and orbital cavity and maxillary bone in 1 patient each (7%). Histological analysis of tumor specimens revealed squamous cell carcinoma in 9 patients (60%), rhabdomyosarcoma in 2 (13%), and small cell carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and Ewing sarcoma in 1 patient each (7%). Two patients experienced recurrences at 1 and 5 months after treatment; these patients died at 5 and 10 months after surgery, respectively. Estimated 5-year recurrence-free survival (RFS) was 86.7%, and estimated 5-year overall survival (OS) was 86.2%; there was no perioperative mortality. None of the patients had new neurological deficits as a result of the surgery, but 5 patients suffered infectious complications from the graft transplanted into the cavity after resection. There were no other perioperative complications. CONCLUSIONS: These authors are the first to describe a technique for extended orbital exenteration with orbital apex skull base resection. The technique provided sufficient margins for gross-total resection of the sinonasal malignancy with orbital apex extension. The estimated 5-year OS and RFS rates were high, and the perioperative complication rate was acceptably low, demonstrating the safety and efficacy of this technique.

Results of immunohistochemical staining for cell cycle regulators predict the recurrence of atypical meningiomas.

OBJECT: The aim of this study was to evaluate the role of certain cell-cycle regulatory proteins in the recurrence of atypical meningiomas. These proteins were analyzed with immunohistochemical staining to identify predisposing factors for the recurrence of atypical meningiomas. METHODS: The authors retrospectively reviewed the medical records of patients with atypical meningiomas diagnosed in the period from January 2000 to June 2012 at the Department of Neurosurgery at Samsung Changwon Hospital and Dong-A University Medical Center. Clinical data included patient sex and age at the time of surgery, presenting symptoms at diagnosis, location and size of tumor, extent of surgery, use of postoperative radiotherapy, duration of follow-up, and recurrence. Immunohistochemical staining for cell-cycle regulatory proteins (p16, p15, p21, p27, cyclin-dependent kinase [CDK] 4 and 6, phosphorylated retinoblastoma [pRB] protein, and cyclin D1) and proliferative markers (MIB-1 antigen, mitosis, and p53) was performed on archived paraffin-embedded tissues obtained during resection. The recurrence rate and time to recurrence were assessed using Kaplan-Meier analysis. RESULTS: Of the 67 atypical meningiomas eligible for analysis, 26 (38.8%) recurred during the follow-up period (mean duration 47.7 months, range 8.4-132.1 months). Immunohistochemically, there was overstaining for p16 in 44 samples (65.7%), for p15 in 21 samples (31.3%), for p21 in 25 samples (37.3%), for p27 in 32 samples (47.8%), for CDK4 in 38 samples (56.7%), for CDK6 in 26 samples (38.8%), for pRB protein in 42 samples (62.7%), and for cyclin D1 in 49 samples (73.1%). Multivariate analysis using the Cox proportional-hazards regression model showed that incomplete resection (HR 4.513, p < 0.001); immunohistochemical understaining for p16 (HR 3.214, p < 0.001); immunohistochemical overstaining for CDK6 (HR 3.427, p < 0.001), pRB protein (HR 2.854, p = 0.008), and p53 (HR 2.296, p = 0.040); and increased MIB-1 labeling index (HR 2.665, p = 0.013) and mitotic index (HR 2.438, p = 0.024) predicted the recurrence of atypical meningiomas after resection. CONCLUSIONS: Findings in this study indicated that p16, CDK6, and pRB protein were associated with the recurrence of atypical meningiomas.