Transition over 35 Years in the Incidence Rates of Primary Central Nervous System Tumors in Shanghai, China and Histological Subtyping Based on a Single Center Experience Spanning 60 Years

Although central nervous system (CNS) tumors are relatively uncommon as compared with other neoplasms, they are associated with a high mortality rate, especially in children (Porter et al., 2010). Intracranial tumors constitute the majority of the CNS tumors and they could be further divided into primary (de novo) and secondary (metastatic) ones in terms of site of origin or malignant and benign variants based on histopathological traits. Specifically, the most common type of malignant and benign primary intracranial tumors are those of neuroepithelial (gliomas) and meningothelial (meningiomas) origin respectively (Kleihues et al., 1993), while lung cancer and breast cancer are most likely to lead to intracranial metastasis (Cordera et al., 2002). Moreover, as compared with their male counterparts, females are reported to be at a higher risk of developing meningioma, whereas lower risk of developing glioma (Kleihues et al., 1993). The heterogeneity of brain tumors is further denoted by the fact


Introduction
Although central nervous system (CNS) tumors are relatively uncommon as compared with other neoplasms, they are associated with a high mortality rate, especially in children (Porter et al., 2010).Intracranial tumors constitute the majority of the CNS tumors and they could be further divided into primary (de novo) and secondary (metastatic) ones in terms of site of origin or malignant and benign variants based on histopathological traits.Specifically, the most common type of malignant and benign primary intracranial tumors are those of neuroepithelial (gliomas) and meningothelial (meningiomas) origin respectively (Kleihues et al., 1993), while lung cancer and breast cancer are most likely to lead to intracranial metastasis (Cordera et al., 2002).Moreover, as compared with their male counterparts, females are reported to be at a higher risk of developing meningioma, whereas lower risk of developing glioma (Kleihues et al., 1993).The heterogeneity of brain tumors is further denoted by the fact

RESEARCH ARTICLE
Transition over 35 Years in the Incidence Rates of Primary Central Nervous System Tumors in Shanghai, China and Histological Subtyping Based on a Single Center Experience Spanning 60 Years Fang Shen 1& , Chun-Xiao Wu 2& , Yu Yao 1& , Peng Peng 2 , Zhi-Yong Qin 1 , Yin Wang 3 , Ying Zheng 2 *, Liang-Fu Zhou 1 * that even histologically benign tumors could jeopardize the survival of the patients and cause severe neurological dysfunction due to their space occupying effects and, occasionally, malignant transformation (Wrensch et al., 2002).
CNS tumors seemed to have increased in incidence over the past 40 years (Fisher et al., 2007) and their incidence rates are reported to be highest in those developed countries in North America and Europe (men, 5.8 per 100,000; women, 4.1 per 100,000), and found to be lowest in Africa (men, 3.0 per 100,000; women, 2.1 per 100,000) (Shin et al., 2010).However, except for ethnic related susceptibility (Fan and Pezeshkpour, 1992) and environmental risk factors (Gurney and Kadan-Lottick, 2001), this discrepancy might also relate to improved accessibility of advanced neuroimaging facilities (Modan et al., 1992;Hoffman et al., 2006) and better CNS tumor registration practices in those developed continents (Davis et al., 1996).For example, based on data from Central Brain Tumor Registry of the United States, the overall incidence rate for primary brain tumors was reported to be 18.1 per 100 000 person-years (Porter et al., 2010).
In China, the first report on the general incidence, age distribution, and preferential sites of CNS tumors in China was published in 1982 (Cheng, 1982), which showed that neuroepithelial and meningeal tumors occurred first and second in terms of frequency, and the age distribution of Chinese patients with CNS tumors was lower than that of Caucasians.Located at the east coast of China, Shanghai is divided into 16 districts and one county.In 1993, a pioneering study (Jin et al., 1993) on cancer incidence trends in urban Shanghai (1972Shanghai ( -1989) ) revealed that the most dramatic increases in incidence rates from 1972-1974 to 1987-1989 were observed for cancers of the gallbladder, colon, and brain/other nervous system and the authors believed these changes could be partially explained by improvements in cancer diagnosis and completeness of the cancer registry.More recently, another two cancer incidence studies reported that, for the period of 1973-2005 in urban Shanghai, brain and spinal tumor was the second most common cancer among children aged 0-14 (Bao et al., 2009) and its incidence rate increased significantly in adolescents and young adults (15 to 49 year-olds) (Wu et al., 2012).
Shanghai has experienced dramatic socioeconomic developments in the past 35 years and this fast modernization is expected to have fundamental impact on the public health of the regional residents.Therefore, given the scarcely available data regarding the incidence, as well as the histological subtypes, of primary CNS tumors in Shanghai, we present here a population based incidence trend analysis between 1973-2007 in urban Shanghai and five-year status quo (2003)(2004)(2005)(2006)(2007) analyses in whole Shanghai city (including both urban and rural areas) for age-, gender-and region-specific incidences.Transverse comparison with other parts of the world was also made by using data from GLOBOCAN 2008.Moreover, we also provide the first detailed report on the histological subtypes of CNS tumors by collecting both the population based data (2003)(2004)(2005)(2006)(2007) and single center based data .

Data source
Population-based data: A resident was defined as any individual registered as permanent resident in Shanghai.All population data (anonymous individual cancer patient registration data) were obtained from the Office for Cancer Prevention at Shanghai Municipal Center for Disease Control & Prevention (CDC) on all CNS tumors (brain, meninges, spinal cord, cranial nerves and other parts of the central nervous system) that were newly diagnosed from 1973 to 2007 (urban Shanghai) or from 2003 to 2007 (the whole city including rural areas).Cancer registration data include basic demographic survey (e.g.date of birth, sex, area of residence) and tumor data (e.g.tumor site, histological diagnosis).Demographic information such as population size and population composition were obtained from the annual reports by Shanghai Municipal Bureau of Public Security.Before 2002, registration data were reported to Shanghai Cancer Institute and tumors were only classified by their locations according to the 9th edition of the International statistical classification of diseases, injuries and causes of death (ICD-9) topography codes.After 2002, registration data were reported to Shanghai Municipal CDC and tumors were classified by both ICD-9 and the second edition of the international classification of diseases for oncology (ICD-O-2, histology codes).Therefore, histological data were only available after 2002.Since it is mandatory for local hospitals to report all residents who suffered from brain tumors to CDC, theoretically, this population based data has 100% coverage.
Single center based data: This study also included all cases of patients who underwent surgical resection or biopsy for primary CNS tumors in the Department of Neurosurgery, Huashan Hospital from 1951 to 2011.Every case was confirmed with pathological examination at the Department of Neuropathology,   2007) were used instead (Louis et al., 2007).Moreover, in an attempt to correspond the hospital based histological subtyping data to the ICD-O codes adopted in CDC based population data, we included: 1) tumors of neuroepithelial tissue; 2) tumors of meningothelial cells; 3) tumors of cranial & spinal nerves; 4) mesenchymal tumors; 5) lymphomas & haematopoietic tumors; 6) germ cell tumors; 7) hemangioblastomas; 8) chordomas.While pituitary tumors, pineal tumors, craniopharyngiomas and spinal cord tumors were excluded.

Methods
Five-year average age-adjusted incidences were calculated by using the direct method, standardized to the 1966 world standard population and presented in per 100,000 population figures.Data regarding incidence rates were stratified by gender (male/female), region (urban/rural), and age groups (in five-year groupings: from 0-to 85+).Unless otherwise stated, reporting of the incidence rates was limited to world-standardized rates for ease of comparison.Trends were expressed as annual percentage change (APC) over the 35-year period by using the joinpoint regression program software (version 3.5.1).A positive or negative APC corresponds to an increasing or decreasing trend, respectively.Statistical analysis was performed by using IBM SPSS Statistics 20.0 for Windows.Categorical variables were analyzed with the Pearson χ 2 test, and continuous variables with the Student's t test.Multiple comparisons of the mean values of continuous variables were first performed with oneway analysis of variance (ANOVA), followed by Fisher's least significant difference (LSD) or Dunnett's post hoc test where appropriate.A P value <0.05 was considered statistically significant.

Population based incidence trends analysis and five-year status quo
Incidence trends analysis: 1973-2007: All patients newly diagnosed with primary CNS tumors, including both benign and malignant tumors of varying histologies and biological behaviors, in urban Shanghai from 1973 to 2007 were recruited for the purpose of analyzing the incidence trends.There was generally a steady increase in both the five-year average crude and age-adjusted incidence rate in both males (crude: 3.5 to 9.05; adjusted: 3.5 to 5.88) and females (crude: 3.17 to 12.32; adjusted: 3.03 to 7) during this period.Specifically, the five-year average crude incidence rate was mildly greater in males before 1992, but surpassed by females since then.Likewise, the mild dominance of males over females in terms of age-adjusted incidence rate was reversed after 1995 (Figure 1A).Trends in age-adjusted incidence rates and the results of the joinpoint analysis were shown in Figure 1B and Table 1.Notably, the incidence rate for males increased significantly between 1973 and 1990 (3.98-5.36,APC=3.47%,P<0.01), but no significant increase was observed between 1991 and 2007 (5.83-6.08,APC=0.80%,P>0.05).A joinpoint was found at the year of 1990 (APC=-2.91%, P<0.01).In contrast, incidence rate for females remained stable increasing throughout the 35year period (3.34-6.89,APC=3.16%,P<0.01) without any detectable joinpoint.Further analysis of the age-specific incidence rate and patients' median age in urban Shanghai suggested that the driving force behind this increasing trend could be largely attributed to the dramatically increased incidence rates in patients of middle aged (>40 years old), especially the elderly aged (>60 years old), groups (Figure 2).Specifically, the incidence rate of the 40-, 50-, 60-, and 80-age groups increased from 4.94 to 6. 5, 6.45 to 11.38, 7.15 to 15.69, 5.43 to 26.69, 10.05 to 32.48 in males and, more evidently, from 4.92 to 6. 93, 5.58 to 13.42, 6.01 to 22.38, 5.23 to 36.86, 1.11 to 42.71 in females.In accordance with this soaring incidence rate in the elderly population, the median age (expressed in years) also increased from 46 to 58.5 in males and from 47 to 64 in females.
Five-year status quo: 2003-2007: During this five-year period, a total of 7166 new cases of primary CNS tumors registered in whole Shanghai city (3174 in males vs. 3992 in females), with 3297 from urban districts (1408 in males vs. 1889 in females), and 3869 from rural areas (1766 in males vs. 2103 in females).At the same period, primary CNS tumors ranked as the 8th most common cancer type (9th in males vs. 7th in females) and accounted for 3.05% of all newly diagnosed cancers (2.48% in males vs. 3.73% in females), with a median age of 59 years old (57 in males vs. 60 in females) and a mortality/incidence ratio of 0.47 (0.58 in males vs. 0.39 in females).During this five-year, the crude incidence rate was 10.58 in whole city (9.33 in males vs. 11.85 in females), 10.67 in urban districts (9.05 in males vs. 12.32 in females) and 10.51 in rural areas (9.56 in males vs. 11.45 in females).After standardization to the 1966 world population, the ageadjusted incidence rate was 6.81 in whole city (6.30 in males vs. 7.31 in females), 6.45 in urban districts (5.88 in males vs. 7.00 in females) and 7.12 in rural areas (6.66 in males vs. 7.57 in females).Moreover, in whole city, the male/female ratio was 0.79 for crude incidence rate (0.73 in urban vs. 0.83 in rural) and 0.86 for age-adjusted incidence rate (0.84 in urban vs. 0.88 in rural).Similarly, for the whole population, the urban/rural ratio was 1.02 for crude incidence rate (0.95 in males vs. 1.08 in females) and 0.91 for age-adjusted incidence rate (0.88 in males vs. 0.92 in females).Statistical analysis revealed females had a significantly higher incidence rate than males (both crude and age-adjusted, P<0.01), and rural areas were significantly higher than urban areas in terms of ageadjusted incidence rate (P<0.01 or <0.05).However, as for the crude incidence rate of the female population, urban areas were significantly higher than rural areas (P<0.05).
From 2003 to 2007, the age-specific incidence rate increased with ages: it was greater than 1.00 ever  .2013.14.12.7385Transition in Primary CNS Tumor Incidences in Shanghai and Histological Subtyping since birth (1.39 in males vs. 2.00 in females), became markedly higher in females than in males when ages were over 35 (4.38 in males vs. 5.21 in females) and reached the peak values in the age group of 80 to 84 (30.62 in males vs. 33.13 in females) (Figure 3A).When compared with data from GLOBOCAN 2008 (published by International Agency for Research on Cancer, IARC, http://globocan.iarc.fr/) the age-specific incidence rate and age-adjusted incidence rate of the World, Developed countries, Developing countries, East Asia and China, we found both males (Figure 3B) and females (Figure 3C) in Shanghai were more likely to be diagnosed with primary CNS tumors [adjusted rate in males: Shanghai (6.3) > Developed countries (5.8) > China (4.3) > East Asia (4.1) > World (3.8) > Developing countries (3.2); adjusted rate in females: Shanghai (7.3) > China (4.5) > Developed countries (4.4) > East Asia (4.1) > World (3.2) > Developing countries (2.8)].Moreover, as indicated by the slope of the curves (incidence rates plotted against age groups) in Figure 3 B & C, Shanghai population, more prominently in females, was characterized with a larger proportion of elderly patients (>60 years old) when compared with other regions.

Discussion
Because Shanghai has many national top-level medical hospitals and medical insurance for urban residents in Shanghai only covered the cost for Shanghai hospitals, patients prefer to be diagnosed and receive neurological surgery locally.And it is mandatory for local hospitals to report all residents who suffered from brain tumors to CDC.Generally speaking, a steadily increasing trend was observed between 1973 and 2007 for both genders, which seemed to be driven mainly by escalating incidence rate in patients of the middle and elderly aged groups.Specifically, females surpassed males in terms of increasing trend since 1990s, and, at present (2003-2007), had a higher incidence rate and median age than males, but with lower M/I ratio.Besides, rural areas had a higher age-adjusted incidence rate than urban areas, while, for females, urban areas had a higher crude incidence rate.Moreover, residents in Shanghai were more likely to be diagnosed with primary CNS tumors when compared with population of the World, Developed countries, Developing countries, East Asia and China.Histological data from both the population (2003)(2004)(2005)(2006)(2007) and Huashan Hospital (1951Hospital ( -2011) ) further revealed tumors of neuroepithelial tissue and meningothelial cells were the two most common histological entities, with male predominance in the former and female predominance in the latter.To our knowledge, this is the single largest and most comprehensive report on the incidence and histological subtypes of primary CNS tumors in Shanghai.
Shanghai Cancer Registry was the first established cancer registry in China.Until today, there is still not much report on the incidence of primary CNS tumor in In the recent five years, 36.86% were tumors of neuroepithelial tissue, 34.20% were tumors of meningothelial cells, and 13.92% were tumors of cranial and spinal nerves.C: 62.86% of the neuroepithelial tumors were astrocytic, 13.53% were oligodendroglial and 7.86% were of ependymal cell.D: Astrocytic tumors were composed of 47.44% glioblastoma, 25.69% diffuse astrocytoma, 14.10% anaplastic astrocytoma, and 9.22% pilocytic astrocytoma DOI:http://dx.doi.org/10.7314/APJCP.2013.14.12.7385Transition in Primary CNS Tumor Incidences in Shanghai and Histological Subtyping both China and Shanghai.The first study in China was published in 1982 (Cheng, 1982) and a recent study (Ding and Wang, 2011) showed the age-adjusted incidence rate of brain tumors in urban Shanghai increased from 3.7 to 6.1 in males and 2.9 to 6.9 in females .But this latter report simply collected data from "Shanghai Cancer Report", which is published by Shanghai Municipal CDC annually, and lacks information on whole city and histological subtypes.Another study (Jiang et al., 2011) reported the prevalence rate for primary brain tumors to be 24.56 per 100,000 in five cities of China (including Shanghai) in the year of 2006.However, in that study, the representative region for Shanghai is Baoshan district, which belongs to the rural part of Shanghai, and patients there have a strong tendency to be referred to Huashan hospital, which is located at the urban district, for diagnosis and surgery.Therefore, our present study incorporates the epidemiological data from the urban and rural districts and may depict a more "actual" picture of the incidence rate in Shanghai.
The remarkably much higher incidence of CNS tumors reported in North America (Zada et al., 2012) and Europe (Caldarella et al., 2011) when compared with that of Asian (Jiang et al., 2011;Manoharan et al., 2012) and African countries (Olasode et al., 2000;Afolayan, 2004;Zalata et al., 2011) may be related to factors including, but not limited to, ethnic, genetic, and epigenetic backgrounds.For instance, improvements in modern medical care system, availability of advanced diagnostic facilities, and even the quality control for the practices of caner data registration would influence the "observed" incidence rate (Ohgaki, 2009;Shin et al., 2010).In this present study, we have identified a steady increase in the age-adjusted incidence rate of primary CNS tumors in both males and females in urban Shanghai (1973Shanghai ( -2007)).Within these 35 years, Shanghai has underwent a dramatic socioeconomic development.Economic boost is also accompanied by dramatic demographic changes.For example, the life expectancy of Shanghai residents in 2011 reached 82.51 years (80.23 for men and 84.80 for women), the highest in mainland China and higher than all but a few countries in the world (City setting records as life expectancy tops 82, http://www.shanghaidaily.com/).Economic prosperity also markedly facilitated the availability of modern medical facilities for Shanghai local residents.
In addition to improvements in life expectancy, availability of advanced diagnostic facilities, and cancer registration practice et al, the increased incidence in Shanghai may also be related to more exposure to risk factors that come along with economic growth, i.e. low frequency electromagnetic fields emitted from mobile phones (Repacholi et al., 2012), bacterial or virus infections (Davis, 2007), and various environmental pollutants (Wrensch et al., 2002).A recent study analyzed the survival of patients after glioma diagnosis in relation to the use of wireless phones and found decreased survival of glioma cases with long-term and high cumulative use of wireless phones (Hardell and Carlberg, 2013).Shanghai was among the first to adopt the use of mobile phones in China (since 1982), and cordless communication has increased rapidly since 1990s and gradually overtaken telephones connected to landlines.By May 2012, an estimate of 20 million mobile phone subscriptions has been reported in Shanghai (http://newspaper.jfdaily.com/).Concerns over adverse health effects have been increasingly discussed with the expansion of this technology.For instance, on 31 May 2011, The WHO/ IARC has classified radiofrequency electromagnetic fields as possibly carcinogenic to humans (Group 2B), based on an increased risk for glioma associated with wireless phone use (http://www.iarc.fr/).However, since the only established risk factor for brain tumors is ionizing radiation exposure, more evidences were needed to establish the relationship between exposure to microwaves emitted from mobile phones and development of brain tumors.
We also attempted to make a transverse comparison of Shanghai five-year status quo (2003)(2004)(2005)(2006)(2007) with that of the World, Developed countries, Developing countries, East Asia and China in 2008.Surprisingly, we found both genders in Shanghai are more likely to be diagnosed with primary CNS tumors when compared with their counterparts in other regions.Besides, residents in Shanghai, especially for females, were featured by a larger proportion of senior patients than other regions.Why females surpassed males in both incidence rate and median age might be explained by the longevity of the women and the fact that elderly population are at a much higher risk of developing cancer.And the difference in histological subtype distribution between the two genders might also explain why men had a higher M/I ratio than women.For example, population data from CDC showed females were more likely to be afflicted with meningioma, which are mostly benign and curable, than males, while males were more likely to have gliomas, which are largely malignant and incurable.
Although this identification of female predominance of meningioma and male predominance of astrocytic tumors from the population data was in accordance with previous report (Wang et al., 2013), the observed higher percentage of meningiomas than gliomas was inconsistent with previous literatures (Kleihues et al., 1993).We think this might be caused by the relatively low histological verification rate of the population data.This high fraction of "unknown/unclassified" tumors (31.95%) were largely diagnosed on the basis of clinical investigation and, therefore, making it impossible to accurately calculate the incidence rate or analyze the trend for each histological subtypes.Besides, population based histological data were only available between 2002 and 2009.Therefore, in an attempt to complement the population data, we then adopted neuropathological data from Huashan Hospital (with 100% histological verification rate) as an alternative source for histological subtyping.Because the neurosurgical department of Huashan Hospital is one of the largest neurosurgery centers in the world (Shi et al., 2012), Shanghai residents who suffered from brain tumors were generally referred to Huashan Hospital for diagnosis and surgery.In contrast with the population data, we found this center treated more neuroepithelial tumors than meningiomas over the past 60 years.Moreover, during the past five years (2007)(2008)(2009)(2010)(2011), neuroepithelial tumors were mostly astrocytic (half of them were GBM), followed by oligodendroglial and ependymal tumors.These single center based data were generally in accordance with previous report (Ohgaki and Kleihues, 2005), which showed gliomas of astrocytic, oligodendroglial, and ependymal origin account for more than 70% of all primary brain tumors, and GBM accounts for approximately 65% of all gliomas.To our knowledge, this is the first report providing such a detailed profiling on histological subtypes of primary CNS tumors in patients from Shanghai and Huashan Hospital.In addition, the number of patients diagnosed with gliomas and meningiomas increased steadily from 1951 to 2011.This increasing trend might result from higher detection rate for asymptomatic gliomas and meningiomas through more frequent use of CT and MRI, as well as the expansion of the elderly population who are at the highest risk of developing brain tumors (Arora et al., 2010).
Because this present report is not an etiological epidemiologic study, it is beyond our goal to provide any concrete explanation for the observed increases in tumor incidence.Nevertheless, the incidence patterns and trends presented here might provide indications or clues for future epidemiologic studies.These future epidemiologic studies (either case-control or cohort studies) could investigate the possible etiology and mechanisms underlying the changes in trend and distribution patterns.In addition, this study also harbored several limitations.For example, due to drawbacks such as incomplete ICD-O coding and low histological verification rate in the population data, especially in early years, it was only possible, and also appropriate, to report percentages, instead of incidence rates, for Shanghai population, making direct comparisons to other reports difficult.Besides, though our single center data is quite valuable, we could not ensure the representativeness of the hospital based data for the population and deny the existence of diagnostic/ referral bias.For example, difficult cases, such as glioma located within eloquent brain regions, meningioma at the skull base, or schwannoma at the cerebellopontile angle, are more likely to be referred to our hospital for surgery, while children with brain tumors would be suggested to be treated at specialized pediatric hospitals.
In conclusion,we presented evidences of an overall increasing incidence of primary CNS tumors over the past 35 years in Shanghai residents.The strength of this paper is the coverage of such a long time period and use of multiple sources to gain insight into histological subtypes.Improved life expectancy, better medical services and cancer registration practices, and more frequent exposure to potential risk factors may all contribute to the observed increases in incidence rate.Future epidemiologic studies are needed to investigate the underlying reasons for the changes in rate trend or pattern and examine the etiology (e.g.environments, genetics, gene-environment interactions).

Figure 1 .
Figure 1.The Crude and Age-adjusted Incidence Rate (per 100,000 population) of Primary CNS Tumors (A) and Joinpoint Regression Analysis for the Trends (B) in urban Shanghai from 1973 to 2007.A: There was generally a steady increase in the five-year average crude and age-adjusted incidence rate in both males (blue solid line) (r crude; p adjusted) and females (red dotted line) (d crude;l adjusted).Moreover, females surpassed males in terms of five-year average crude and age-adjusted incidence rate since 1992 (g) and 1995 ( ).B: Joinpoint regression showed the incidence rate for males (p: observed value; blue solid line: fitted value) increased first(1973-1990), then plateaued (1991- 2007)  and a joinpoint (r) was found in 1990 (g).While the rate for female (l: observed value; red dotted line: fitted value) remained increasing throughout the 35-year period and no joinpoint (d) was detected Institute of Neurology, Huashan Hospital, while those with uncertain or ambiguous pathological diagnosis were excluded.For the period of1951-1999, the first (1979)   and second edition (1993) of WHO classification of CNS tumors were successively adopted in our hospital.Since 2000 and 2007, the third edition (2000) and fourth edition (2007) were used instead(Louis et al., 2007).Moreover, in an attempt to correspond the hospital based histological subtyping data to the ICD-O codes adopted in CDC based population data, we included: 1) tumors of neuroepithelial tissue; 2) tumors of meningothelial cells; 3) tumors of cranial & spinal nerves; 4) mesenchymal tumors; 5) lymphomas & haematopoietic tumors; 6) germ cell tumors; 7) hemangioblastomas; 8) chordomas.While pituitary tumors, pineal tumors, craniopharyngiomas and spinal cord tumors were excluded.

Figure 2 .Figure 3 .
Figure 2. The Age-specific Incidence Rate (per 100,000 population) and Median Age (expressed in years) of the Males (A) and the Females (B) in Urban Shanghai Between 1973 and 2007.During this period, the five-year average incidence rate (left Y axis) increased markedly in the 40-, 50-, 60-, 70-and 80-age groups in both genders.The median age (right Y axis) also increased from 46 to 58.5 in males and 47 to 64 in females

Figure 4 .
Figure 4. Histological Subtyping of Primary CNS Tumors in Patients Treated at the Department of Neurosurgery, Huashan Hospital for the Past 60 Years (1951-2011) (A) and in the Recent Five Years (2007-2011) (B-D).A: Tumors of neuroepithelial tissue, meningothelial cells, and cranial and spinal nerves were the three most common histological subtypes during the past 60 years.B:In the recent five years, 36.86% were tumors of neuroepithelial tissue, 34.20% were tumors of meningothelial cells, and 13.92% were tumors of cranial and spinal nerves.C: 62.86% of the neuroepithelial tumors were astrocytic, 13.53% were oligodendroglial and 7.86% were of ependymal cell.D: Astrocytic tumors were composed of 47.44% glioblastoma, 25.69% diffuse astrocytoma, 14.10% anaplastic astrocytoma, and 9.22% pilocytic astrocytoma

6. 56 Table 1. Annual Percentage Changes (APC) for Age-adjusted Incidence Rate of Primary Central Nervous System Tumors in Urban Shanghai Between 1973 and 2007
*Incidence rate was expressed as per 100,000 population (data from Shanghai Municipal Center for Disease Control & Prevention)

Table 2 . Population Based Histological Subtyping of Primary Central Nervous System Tumors in Shanghai from 2003 to 2007
Hospital, whose neurosurgical department is the largest center in Asia-Pacific(Shi et al., 2012).Patients in Shanghai are generally referred to Huashan Hospital for neurosurgical operations(Wang et al., 2008).According to this single center data, a total of 38994 cases of