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Surgical Experience of Infratentorial Meningiomas : Clinical Series at a Single Institution during the 20-Year Period

Objective Based on surgical outcomes of patients with infratentorial meningiomas surgically treated at our institution, we analyzed the predictors for surgical resection, recurrence, complication, and survival. Methods Of surgically treated 782 patients with intracranial meningioma, 158 (20.2%) consecutive cases of infratentorial location operated on between April 1993 and May 2013 at out institute were reviewed retrospectively. The patients had a median age of 57.1 years (range, 16--77 years), a female predominance of 79.7%, and a mean follow-up duration of 48.4 months (range, 0.8--242.2 months). Results Gross total resection (Simpson's grade I & II) was achieved in 81.6% (129/158) of patients. Non-skull base location was an independent factor for complete resection. The recurrence rate was 13.3% (21/158) and the 5-, 10-, and 15-year recurrence rates were 8.2%, 12.0%, and 13.3%, respectively. Benign pathology, postoperative KPS over than 90, low peritumoral edema, and complete resection were significantly associated with longer recurrence-free survival rate. The 5-, 10-, and 15-year survival rates were 96.2%, 94.9%, and 94.9%, respectively. Benign pathology, postoperative KPS over than 90 and complete resection were significantly associated with a longer survival rate. The permanent complication rate was 13% (21/158). Skull base location and postoperative KPS less than 90 were independent factors for the occurrence of permanent complication. Conclusion Our experience shows that infratentorial meningiomas represent a continuing challenge for contemporary neurosurgeons. Various factors are related with resection degree, complications, recurrence and survival.

INTRODUCTION ly treated at our institution to postulate the predictors for surgical resection, recurrence, complication, and survival.

Patients
The study is in compliance with the Declaration of Helsinki (Sixth Revision, 2008). This study fulfils all the requirements for patient anonymity was approved by the institutional review board. Between April 1993 and May 2013, 782 case of intracranial meningioma were surgically resected at our institution. Among these cases, 158 patients (20.2%) were diagnosed with infratentorial meningioma by means of radiological studies [nonenhanced and enhanced computed tomographic (CT) scanning and magnetic resonance imaging (MRI)] and their surgical records. Recurred cases were excluded from this study.

Analysis variables
To define the clinical and radiological characteristics of the patients, several variables such as age, sex, presenting symptoms, pathology, tumor features (size, location, peritumoral edema), preoperative and postoperative KPS, postoperative transient/ permanent complications, recurrence and survival rate were evaluated. These clinicoradiological variables are summarized in Table 1.
The patients consisted of 32 males and 126 females (female predominance, 79.7%), with a median age of 57.1 years (range, 16-77 years). The most common presenting symptoms were headache, followed by dizziness and disturbance of gait. Some patients presented with mental change, another with cranial nerve palsy. The exact location of the patients was decided by radiological study and operation records, with regard to the origin of the mass, including tentorial meningioma in 39 patients, cerebellopontine angle (CPA) in 75 patietns, petroclival in 21 patients, peritorcular in 8 patients, cerebellar convexity in 7 patients, foramen magnum in 6 patients, and jugular foramen in 2 patients.
Tumor locations were classified into 3 groups according to their origin site (Group I, cerebellopontine angle & cerebellar convexity; Group II, tentorial & peritorcular; Group III, petroclival & other skull base location). Based on T1-weighted enhanced & T2-weighted non-enhanced MRI, the maximal size of the tumor and peri-tumoral edema was evaluated. Four centimeter was cut-off value as the size parameter (<4 cm vs. ≥4 cm). According to the peri-tumoral edema, the patients were divided into two groups [none or minimal (<5 mm in edema thickness) vs. moderate or severe (≥5 mm in edema thickness)].
The extent of tumor resection was classified according to the Simpson's classification 22) . Gross total resection was defined as Simpson's Grades I and II resection without any visible tumor remnant on surgical finding and follow-up MRI. All tumors were graded pathologically according to the World Health Organization (WHO) classification system. According to the pa-mortality 2,11,20,28) . Despite these improvements, surgery for infratentorial meningiomas is still associated with high morbidity and complications. In the present study, we analyzed surgical outcomes of patients with infratentorial meningiomas surgical-

Overall survival
The incidence of death rate was 5.0% over follow-up period (8/158). The surgery-related mortality which the death occurred within one month after resection was 3.16% in this study (5/158). The 5-, 10-, and 15-year survival rates were 96.2%, 94.9%, and 94.9%, respectively (Fig. 3). The results of analyses of the variables that could be correlated with survival time are shown in Fig. 4 and Table 4.
On univariate analysis, pathology, location, size, postopera-thology had been classified by WHO grade that grade I in 148 patients, grade II & III in 10 (9 patients in Grade II & 1 in III). On follow-up MRI, new enhancing mass in completely resected case or re-growing symptomatic mass in non-completely resected case was regarded as a recurred lesion. Surgery-related complication was defined as a new developed neurological deficit or aggravated pre-existing deficit. The postoperative complications were separated of transient and permanent. The transient complication was defined as the new or aggravated postoperative problem resolved generally within 3-6 months after the operation. If the problem persisted or needed another operation, it was regarded as the permanent complication. The pre-and post-operative clinical status was quantified retrospectively using the KPS. The time to measure of post-operative KPS was 6 months after the operation. Good performance status was defined as above KPS 80. All surviving patients were monitored; the mean duration of follow-up was 48.4 months with a range of 0.8 to 242.2 months.

Statistical analysis
Recurrence-free survival (RFS) was calculated as the time from surgery to the date of recurrence. The probability of RFS was analyzed according to the Kaplan-Meier method and compared with the log-rank test. Overall survival was also calculated as the time from surgery to the date of death or last followup visit. For the multivariate analysis, independent prognostic factors were determined using the Cox's proportional hazards model. The relation between resection degree/permanent complication occurrence and categorical variables was compared by using a chi-square test or Fisher-exact probability test. Furthermore, binary logistic regression test was applied for multivariate analysis. All statistical analyses were performed using SPSS version 20.0 software program for Windows (Chicago, IL, USA). The level of significance was set at p<0.05.

Resection
Commonly used approaches were lateral or midline suboccipital. For some cases, far lateral, subtemporal, or orbitozygomatic route was selected to resect the lesion located on skull base region. In our series, 129 patients (81.6%, 129/158) were classified into Simpson' s grade I and II, 28 patients (17.7%) into grade III and IV and 1 patient (0.6%) into grade V. On univariate analysis, female (p=0.019), non-skull base location (p<0.001) and postoperative KPS over than 90 (p=0.012) were significantly related with the possibility of complete resection (    tion, motor weakness, hydrocephalus, and infection. The results of analyses of the variables that could be correlated with permanent complications are shown in Table 5. On univariate analysis, location, preoperative symptom, and preoperative KPS showed statistical significance. The tumor location was important factor for development of permanent complication (8.1% in group I vs. 2.3% in group II, 28.0% in group III, p=0.002). The group located at skull base showed higher possibility of permanent complication than the non-skull base group (28.0% vs. 6.0%, p=0.001). The patient with brain stem or cranial nerve sign showed higher possibility for postoperative complication, compared to the patient with other minor symptoms (19.0% vs. 7.4%, p=0.043). The patient with low level of postoperative KPS (<90) was also significantly associated with permanent complication (37.1% vs. 3.5%, p<0.001).

Complication
Permanent complication rate was 13% (21/158) in our study. Most common permanent complication is cranial nerve injury (42.9%) followed by operation-related hemorrhage or infarc- for postoperative outcome by some authors 3,8) . In other reports, however, tumor size did not have any significant influence on surgical morbidity 10,15,24) . Some authors have pointed out that outcome is less favorable in elderly patients with meningiomas located at the base of the skull, especially the posterior fossa 1,2,4,5,20) . Other authors reported that KPS present a relationship of postoperative outcome 13,29) . In consideration of previous studies, surgery for infratentorial meningioma is still associated with significant postoperative deficits, thus confirming that these lesions represent a great challenge even for contemporary neurosurgeons 25) .
have been operated on in recent years and a few surgical series were reported in the literature 22) . And, surgical results with infratentorial meningiomas have much improved during the last two decades, but radical removal continues producing a high morbidity rate and still occasional mortality 19) .
In intracranial meningioma resection, surgical outcome and its predictive factors were not fully identified. Some authors mentioned the presence of peritumoral edema as a predictor of poor outcome in elderly patients 3,8,13) , whereas others did not find any relationship between edema and unfavorable outcome 10,23) . Tumors size has been considered as a predictive factor Since the first classification of infratentorial meningiomas was proposed by Cushing and Eisenhardt in 1938, Castellano and Ruggiero subdivided these tumors into five groups; cerebellar convexity, tentorium, posterior petrous, clivus and foramen magnum meningiomas 9) . Based on this classification, total 158 patients with infratentorial meningiomas underwent surgery during 20 years in out hospital (20.2%, in total 782 patients with intracranial meningiomas).

Resection
Although a radical resection of these histologically benign tumors is the ideal objective of surgical therapy, this is not always possible 25) . During surgical planning, it should be kept in mind that meningiomas show a marked tendency to invade dura, nerves, and surrounding bone 21) . The dura surrounding the tumor should be resected and the bony invasion should be drilling until normal bone is seen 27) . And vascular encasement, although representing an additional surgical problem, by itself did not generally prevent the pursuance of gross total removal 25) . In fact, as noted by Sekhar et al. 28) , blood vessels are surrounded by an arachnoid plane that can be carefully dissected by experienced surgeons. Subtotal resection carries a lower risk of morbidity than radical excision, but residual tumor may lead some patients to the initial clinical scenario sooner or later, and reoperation is usually less successful and more risky than initial surgery, particularly when the patient is given radiotherapy after the initial operation 18,28) . At the present moment the majority of authors recommend subtotal resection for old patients or when there are factors defying complete removal 7,12,17) . The critical factors influencing the possibility of radical and safe resection of meningiomas are tumor-vascular relationships and the integrity of the arachnoid plane between the tumor and the brainstem 19) . In our series, non-skull base location was a significant factor for complete resection.

Recurrence
The recurrence rate of infratentorial meningiomas is particularly difficult to estimate because of differences in the reported series regarding the rates of radical excision, the methods of assessment of complete removal, the follow-up periods, the average age of the patients and the percentage of patients receiving postoperative radiotherapy 19) . Some studies have shown that meningiomas may recur after an apparently radical excision, but it is clear that completeness of resection is the main factor preventing regrowth in all locations 1,4,17) . Others indicated that frozen section analysis for intraoperative pathological sample is appropriate since a diagnosis of meningioma will direct that bone adjacent to the tumor site of origin be removed to reduce recurrence rate 30) . In our series, non-benign pathology, non-complete resection, moderate or severe degree of peritumoral edema, and low postoperative KPS (<90) were independent factors for short RFS in multivariate analysis. It is not difficult to anticipate that meningioma with high pathological grade or non-complete

Survival and complication
Considering that the goal of surgery of meningiomas is gross total resection with minimal morbidity and low mortality 14) , single-stage total removal should be attempted 27) . But the attempt for aggressive surgical resection continues producing a high morbidity rate and still occasional mortality 19) . The perioperative mortality rate in the surgical management of infratentorial meningiomas has varied from 0-15.7% 25) . In our series, the total death rate during the follow-up period was 5.0% (8/158) of case. The postoperative mortality rate, as defined patients ware expired within 30 days after initial operation, was 3.16% (5/158). Non-benign pathology, non-complete resection, and resection frequently recurred after the surgery. The postoperative KPS was higher, the recurrence rate was lower. It means, in our opinion, that the group of postoperative KPS under 80 tend to have subtotal resection because of intraoperative events, such as accidental injuries or poor dissection plane of cranial nerves, surrounding en-passing vessels, or brain stem, even though initial attempt for gross total resection. Therefore, these groups seem to have lower postoperative KPS, have higher recurrence rate. The more have edema, the more have recurrence rate. This is probably because the patients have moderate to severe edema tend to have high-grade pathology, large size, or poor dissection plane, leading to eventual recurrence of tumor. foramen magnum or jugular foramen, surgical resection for these lesions have high risk of permanent complication, even though experienced neurosurgeon.

CONCLUSION
In this study, gross-total resection was achieved in 81.6% of the cases and related with non-skull base location. The recurrence rate was 13.3% and longer RFS was associated with benign pathology, postoperative KPS over than 90, low peritumoral edema, and complete resection. The 5-, 10-, and 15-year overall survival rates were 96.2%, 94.9%, and 94.9%, respectively. Benign pathology, postoperative KPS over than 90 and complete resection were independent factor for a longer survival. The permanent complication was developed in 13% of the patients and related with low postoperative KPS (<90) were independent factors for short survival in multivariate analysis. In our study, the group of gross total resection has more survival rate. It is presumably related with recurrence rate and postoperative condition. Patients with high postoperative KPS represented lower complication rate and good postoperative condition. For this reason, the postoperative KPS was significant predictive factor of survival.
As previously reported by several authors, the most common postoperative complication was found to be cranial nerve paresis or palsy 2,11,20,26) . In our study, the permanent neurological deficits occurred in 12% (19/158) of case and the most common type is cranial nerve injury (47%, 9/19). In multivariate analysis, skull base location and low postoperative KPS were independent factors for the occurrence of permanent complication. Because of more difficult anatomical factor in petroclival, skull base location and postoperative KPS less than 90. Our results show relatively low morbidity and mortality rates, and good surgical resection and low recurrence rate, compare to the results of past, due to significant advances contemporary neurosurgical techniques, neuromonitoring and neuroanestehsia. However, infratentorial meningioma still has been a challenge for neurosurgeon because of their close to critical vascular and nerves structure. To achieve the goal that a little more lower morbidity and mortality, the surgeon need to consider of these factors and try to appropriate surgical planning of each case.