Incidence and Mortality of Spontaneous Subarachnoid Hemorrhage in Hong Kong from 2002 to 2010: A Hong Kong Hospital Authority Clinical Management System Database Analysis

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Incidence and Mortality of Spontaneous Subarachnoid Hemorrhage in Hong Kong from 2002 to 2010: A Hong Kong Hospital Authority Clinical Management System Database Analysis George Kwok Chu Wong, Yvonne Yik Wun Tam, Xian Lun Zhu, Wai Sang Poon

Key words Chinese - Hong Kong - Incidence - Mortality - Subarachnoid hemorrhage -

Abbreviations and Acronyms CI: Confidence interval CMS: Clinical Management System HA: Hospital authority IRR: Incidence risk ratio SAH: Subarachnoid hemorrhage Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong To whom correspondence should be addressed: George Kwok Chu Wong, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2014) 81, 3/4:552-556. http://dx.doi.org/10.1016/j.wneu.2013.07.128 Journal homepage: www.WORLDNEUROSURGERY.org

- BACKGROUND:

Ninety-five percent of the Hong Kong population is Chinese, and no previous epidemiological study has focused on spontaneous subarachnoid hemorrhage (SAH) in Hong Kong. These data would have significant public health implications and can guide future resource allocations and service development in Hong Kong. The aim of this study was to investigate the local incidences of spontaneous SAH and 1-year mortality rates in Hong Kong, with the respective time trends in recent years.

- METHODS:

Data from the Clinical Management System database of the Hong Kong Hospital Authority were used to examine the incidence of SAH and 1-year mortality rates among the Hong Kong population for the 2002e2010 period. Agestandardized incidence rates were calculated by the direct method using the standard population given in World Health Organization World Standard Population 2000e2025.

- RESULTS:

Crude SAH incidences increased from 5.5 per 100,000 person-years in 2002 to 7.5 in 2010. Standardized SAH incidences increased from 4.1 per 100,000 person-years in 2002 to 5.6 in 2010. Crude 1-year mortality rates decreased from 43% in 2002 to 19% in 2010, and the standardized 1-year mortality rate decreased from 38% in 2002 to 19% in 2010.

Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.

- CONCLUSION:

The Hong Kong SAH incidence was 7.5 per 100,000 personyears in 2010, and an increasing trend over time was noted. The 1-year mortality rates decreased from 43% in 2002 to 19% in 2010, in accordance with the worldwide trend.

INTRODUCTION Evidence from developed countries suggests that 1 in 20 adults is affected by stroke (11, 16), and the incidence of acute cerebrovascular events (stroke and transient ischemic attack) currently exceeds the incidence of acute coronary heart disease (10, 23). This worldwide stroke epidemic and the well-recognized medicosocial consequences of stroke justify the need of worldwide stroke epidemiology, which will in turn advance our understanding of stroke frequency and determinants in various populations, enabling better health care planning (10). Although aneurysmal subarachnoid hemorrhages (SAHs) account for only 3%e5% of all strokes, the loss of productive life years is equal to that caused by ischemic strokes as a result of the devastating consequences and the propensity of SAHs to

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affect patients who are younger than 66 years of age. This remains the case, despite encouraging data showing a reduction in mortality during the last two decades (20, 21, 27). Recent studies have also shown that aneurysmal SAHs cause excess mortality for 12 months, after which other causes of death become dominant (14), and that there are geographical differences in case fatality rates (21). Locally, we also observed significant loss of cognitive function and reduction in quality of life in survivors after SAH (31, 33, 34). The incidence of SAH has been estimated to be approximately 9 per 100,000 person-years, with geographic variations and association with age (9, 10, 15). A recent study suggested that the overall stroke incidence among Hong Kong

Chinese (classified as a high-income country) was greater than in many similar countries and that the incidence of hemorrhagic stroke had increased among the young population (6). The most reliable data on stroke incidence and case fatality come from population-based incidence studies. A systemic review of population-based incidence studies published in 2009 showed a divergent, statistical significant trend in stroke incidence rates during the past four decades (10). Although detailed epidemiologic data in the hospitalization of ischemic stroke are available in the literature, similar data are relatively few for SAH (17). Ninety-five percent of the Hong Kong population is Chinese, and no previous epidemiological study has focused on the incidences of SAH with regard to

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occurrence (grouped as 2002e2004, 2005e2007, and 2008e2010) (22). Agestandardized incidence rates were calculated by the direct method using the World Health Organization World Standard Population 2000e2025 as the standard population (1). Poisson regression models were used to examine the time trends in SAH incidence. Incidence risk ratios (IRRs) were estimated from the model. An IRR >1 indicated association with greater incidence, and vice versa. Logistic regression was used to quantify the relation between the 1-year mortality and the year of occurrence. The results were calculated as the percentage change in the 1-year mortality rate per calendar year increase with corresponding 95% CIs. Variables for adjustment were sex and age.

Nevertheless, the incidence rate was probably slightly underestimated in our dataset (6). The study was approved by the joint ethics committee of the Chinese University of Hong Kong and Hospital Authority of Hong Kong.

age and time trends and on the 1-year mortality rates with regards to time trends in Hong Kong (18, 32). AIMS This study investigated the incidence of SAH and 1-year mortality rates in Hong Kong. These data are important components in understanding geographic differences of SAH incidence and mortality. They have significant public health implications and can guide future resource allocations and service development in Hong Kong.

Definitions For this study, spontaneous (nontraumatic) SAH was defined as any case given the International Classification of Diseases, 9th revision code 430 as a principal diagnosis during the first admission within an episode (26). Admissions that had the same principal diagnosis as the previous discharge were considered the same episode. Age, sex, and 1-year mortality were retrieved.

METHODS Data Data from the Clinical Management System (CMS) database of the Hong Kong Hospital Authority (HA) were used to examine the incidence and mortality rates among the Hong Kong population from 2002 to 2010. The CMS is a computerized system for all aspects of clinical management that was implemented by the HA in 1995. Since 1999, it has been used by all hospitals run by the HA. The diagnoses for hospital admissions were coded by International Classification of Diseases, 9th Revision, Clinical Modification and verified by experts in the HA. Patients with severe stroke who died before arrival at HA hospitals also were included in our dataset. More than 90% of all hospital admissions for stroke were to hospitals run by the HA (12); the HA admission data used in this study, therefore, provided a good reflection of the stroke cases in Hong Kong.

Statistical Analyses SPSS for Windows Version 15.0 (SPSS Institute, Chicago, Illinois, USA) and MedCalc Version 12.2.1.0 (MedCalc, Ostend, Belgium) were used for statistical analyses. Statistically significant difference was defined as a P < 0.05. The Bonferroni correction for multiple comparisons was applied to age-specific incidence risk ratio analyses. The numbers of SAH episodes each year between 2002 and 2010 were recorded. Incidence rates were presented as episodes per 100,000 person-years with a 95% confidence interval (CI). Age-specific SAH incidence rates (0e24, 25e34, 35e44, 45e54, 55e64, and
65 years) were calculated by the use of age-specific population sizes from the Hong Kong Census and Statistical Department. These rates were broken down by year of

RESULTS Overall Distribution From 2002 to 2010, there were 3759 episodes (from 356 to 517 episodes per year) of hospital admissions of spontaneous SAH, unrelated to trauma, identified from the CMS database in Hong Kong; 2373 (63%) of the patients were female. Age (mean  SD) was 59  14 years. Incidence and 1-Year Mortality Rates Crude SAH incidence increased from 5.5 per 100,000 person-years in 2002 to 7.5 in 2010, and standardized SAH incidences increased from 4.1 per 100,000 personyears in 2002 to 5.6 in 2010 (Table 1). The crude SAH incidence between 2008 and 2010 was significantly greater than the

Table 1. Incidence of SAH and 1-Year Mortality Rates in the 2002e2010 Period Calendar Year

2002

2003

2004

2005

2006

2007

2008

2009

2010

SAH episodes

368

356

396

413

389

374

440

506

517

Crude SAH Incidence

5.5 (4.9e6.1) 5.3 (4.8e5.9) 5.9 (5.3e6.5) 6.2 (5.6e6.8) 5.7 (5.1e6.3) 5.4 (4.9e6.0) 6.4 (5.8e7.0) 7.4 (6.7e8.0) 7.5 (6.9e8.2)

Standardized SAH incidence 4.1 (3.6e4.6) 3.8 (3.4e4.3) 4.3 (3.8e4.8) 4.5 (4.1e5.1) 4.1 (3.6e4.6) 4.0 (3.5e4.5) 4.7 (4.2e5.3) 5.4 (4.8e6.0) 5.6 (5.0e6.2) One-year mortality

148

81

99

81

92

102

101

102

110

Crude mortality rate

43 (36e50)

23 (18e28)

27 (22e33)

20 (16e24)

24 (19e29)

27 (22e33)

23 (19e28)

20 (16e24)

19 (16e24)

Standardized mortality rate

38 (31e47)

22 (17e29)

25 (19e31)

18 (14e24)

23 (18e29)

27 (21e34)

23 (18e29)

20 (15e25)

19 (15e24)

Values are 95% confidence intervals in parentheses. Incidence per 100,000 person-years; rate as 100 persons. Standardization: World Health Organization World Standard Population 2000e2025. SAH, subarachnoid hemorrhage.

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crude incidence between 2002 and 2004 (7.1 and 6.1 per 100,000 person-years, respectively; IRR 1.15; 95% CI 1.06e1.24). The crude SAH incidence between 2008 and 2010 was significantly greater than between 2002 and 2004 among the 35e44 and 55e64 age groups, IRR 1.7 (95% CI 1.3e2.1) and 1.3 (95% CI 1.1e1.6), respectively (Table 2). Crude 1-year mortality rates decreased from 43% in 2002 to 19% in 2010, and the standardized 1-year mortality rate decreased from 38% in 2002 to 19% in 2010. The decreasing trend in crude 1-year mortality rates from 2002 to 2010, after adjustments for age and sex, was confirmed with linear regression (odds ratio, 0.93; 95% CI 0.90e0.96; P < 0.001). DISCUSSION In this study, the number of crude SAH incidences in 2010 was 7.5 per 100,000 person-years, compared with 9 per 100,000 person-years in a meta-analysis published in 2007 (9). However, our data showed an increase in the incidence of SAH in Hong Kong during a similar time period, in contrast to a moderate decrease reported in the same meta-analysis. We also assessed mortality rate at 1 year. In a recent report from a Finnish database, aneurysmal SAH caused excess mortality for 12 months, after which other causes of death became dominant (14). They found a 1-year mortality rate of 27%.

Our 1-year mortality rate in 2010 compared favorably with the published literature and showed a similarly decreasing trend over time (21). In Asia, incidence of aneurysmal SAH is noted to be greater in Japan than in the current Hong Kong study targeting mainly Chinese (9). Intracranial aneurysms and resulting SAH are thought to arise from the action of multiple genetic and environmental risk factors. Risk of intracranial aneurysms and resulting SAH increases with smoking and hypertension and is greater among female and those with family history but interestingly decreases with hypercholesterolemia (13, 19, 28, 29). It is of interest to note that prevalence of both hypertension and smoking in Japan was nearly doubled that of Hong Kong: hypertension 45% versus 27% and smoking 22% versus 12% (4, 8, 24, 30). The degree of these modifiable risk factors in accounting for the difference in incidences remains to be determined in future studies. In Hong Kong, the prevalence of hypertension remained stable, and the incidence of smoking showed a mild decrease over the past few years and therefore cannot account for the increase in incidences observed in the current study (3, 5). Genome-wide association studies to identify common variants that contribute to intracranial aneurysms using multistage multinational cohorts (including Japanese but not Chinese) are being reported (2, 36, 37). The loci on chromosomes 8q and 9p

Table 2. Time Trend of SAH Incidence in Different Age Groups Fitted Incidence Rates Age Group, Years All

2005e2007 vs. 2002e2004

2008e2010 vs. 2002e2004

2002e2004

2005e2007

2008e2010

IRR

95% CI

IRR

95% CI

6.1

5.5

7.1

0.9

0.8e1.0

1.2*

1.1e1.2

y

0e24

1.5

1.6

1.1

1.1

0.4e3.1

0.1

0.2e0.0

25e34

1.3

0.9

1.2

0.7

0.5e1.2

0.9

0.6e1.4

35e44

3.2

3.8

5.3

1.2

1.0e1.6

1.7*

1.3e2.1

45e54

9.7

8.9

10.8

0.9

0.8e1.1

1.1

1.0e1.3

55e64

15.1

13.5

20.3

0.9

0.7e.1

1.3*

1.1e1.6

65þ

19.4

16.7

18.1

0.9

0.7e1.0

0.9

0.8e1.1

SAH, subarachnoid hemorrhage; IRR, incidence rate ratio; CI, confidence interval. *IRR significantly greater than 1: P < 0.004. yIRR significantly smaller than 1: P < 0.004.

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are related to the formation and maintenance of endothelial cells, suggesting a role in development and repair in the vasculature (36). The loci on chromosomes 18q, 13q, and 10q play a role in cellcycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair (36). Recently, a 4q locus at immediate proximity to endothelin receptor type A within a predicted regulatory region also provides genetic evidence linking endothelins to intracranial aneurysm pathogenesis (37). Similarly, in a genome-wide association analysis of copy number variations in Japanese patients with aneurysmal SAH, investigators discovered 1232 candidate genes (2). It is thus likely that intracranial aneurysms and the resulting SAH arise from the action of multiple genetic and environmental risk factors. No large-scale study has yet assessed any systemic differences in susceptible loci between Chinese and Japanese. The current study is subject to a number of limitations. Administrative databases have known limitations (35). The diagnosis of SAH was based on computed tomography of the head. Causes of SAH could not be investigated in available electronic database, although 85% were believed to be aneurysmal (7). Prognostic factors such as aneurysm characteristics, admission neurological status, and hemorrhage burden were not assessed. Neurologic outcomes were not available. Risk factors such as hypertension and smoking could not be accurately retrieved from the administrative database, which prohibit analysis of the relationship between time trend and risk factors. In the current study we used a cold pursuit method (retrospective identification of cases through a computerized medical record system) rather than a hot pursuit method (prospective screening of hospital admissions and referrals), even though the former should be adequate for case ascertainment (25). The most significant deficiency of our study was that coding accuracy and missing entries could not be assessed. Given that it was a retrospective study, on-site quality control checks could not be performed. The incidences in the current study might have been slightly underestimated as some patients (<10%) visited non-HA hospitals

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and some mild cases were not hospitalized. However, no unified linkage system was available for these non-HA hospitals, and the characteristics of patients that were included and not included in the current database were not available. Assuming a constant underestimation pattern, it is unlikely that the analysis of the trends was affected. Another potential limitation was the lack of details for the episodes. Ethnicity could not be confirmed, although 95% of the patients were presumed to be Chinese. CONCLUSIONS The incidence of SAH in Hong Kong was 7.5 per 100,000 person-years in 2010, and an increasing trend over time was noted. The 1-year mortality rates decreased from 43% in 2002 to 19% in 2010, in accordance with the worldwide trend. REFERENCES 1. Ahmad OB, Boschi-pinto C, Lopez AD, Murray CJ, Lozano T, Inoue M: Age Standardization of Rates: A New WHO World Standard. GPE Discussion Paper Series, No. 31. Geneva: EIP/GPE/EBD, World Health Organization; 2001. 2. Bae JS, Cheong HS, Park BL, Kim LH, Park TJ, Kim JY, Pasaje CF, Lee JS, Cui T, Inoue I, Shin HD: Genome-wide association analysis of copy number variations in subarachnoid aneurysmal hemorrhage. J Human Genet 55:726-730, 2010. 3. Bilguvar K, Ysuno K, Niemela M, Ruigrok YM, von und zu Fraunberg M, van Duijn CM, van den Bergh LH, Mane S, Mason CE, Choi M, Gaal E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jaaskelainen JE, Palotie A, Inoue I, Lifton RP, Gunel M: Susceptibility loci for intracranial aneurysm in European and Japanese population. Nat Genet 40:1472-1477, 2008. 4. Centre for Health Protection. Hypertension. Available at: http://www.chp.gov.hk/en/content/9/ 25/60.html. Accessed March 11, 2013. 5. Centre for Health Protection. Smoking. Available at: http://www.chp.gov.hk/en/content/9/25/8806. html. Accessed March 11, 2013. 6. Chau PH, Woo J, Goggins WB, Tse YK, Chan KC, Lo SV, No SC: Trends in stroke incidence in Hong Kong differ by stroke subtype. Cerebrovasc Dis 31: 138-146, 2011. 7. Connolly ES, Rabinstein AA, Cauhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P; on behalf of the American Heart Association Stroke Council: Council on Cardiovascular Radiology and Intervention,

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Council on Cardiovascular Nursing, Council on Cardiovascular Surgery and Anesthesia, and Council on Clinical Cardiology: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 43:1711-1737, 2012. 8. COSH. The government released the 2012 Hong Kong smoking prevalence. Available at: http://www. smokefree.hk/content/web.do?page¼news20101213. Accessed March 11, 2013. 9. de Rooij NK, Lin FH, van derPlas JA, Algra A, Rinkel GJ: Incidence of subarachnoid haemorrhage: a systemic review with emphasis on region, age, gender, and time trends. J Neurol Neurosurg Psychiatry 78:1365-1372, 2007. 10. Feigin VL, Lawes CM, Bennett DA, BarkerCollo SL, Parag V: Worldwide stroke incidence and early case fatality reported in 56 populationbased studies: a systemic review. Lancet Neurol 8: 355-369, 2009. 11. Hachinski V: The 2005 Thomas Willis Lecture: stroke and vascular cognitive impairment: a translational and transactional approach. Stroke 38:1396, 2007. 12. Hospital Authority of Hong Kong: Hospital Authority Statistical Report. Available from: http://www. ha.org.hk/upload/publication_15/321.pdf. Accessed June 11, 2012. 13. Inagawa T: Risk factors for the formation and rupture of intracranial saccular aneurysms in Shimane, Japan. World Neurosurg 73:155-164, 2010. 14. Karamanakos PN, von und Zu Fraunberg M, Bendel S, Huttunen T, Kurki M, Hernesniemi J, Ronkainen A, Rinne J, Jaaskelainen JE, Koivisto T: Risk factors for three phases of 12-month mortality in 1657 patients from a defined population after acute aneurysmal subarachnoid hemorrhage. World Neurosurg 78:631-639, 2012. 15. Lai L, Morgan MK: Incidence of subarachnoid haemorrhage: an Australian national hospital morbidity database analysis. J Clin Neurosci 19: 733-739, 2012. 16. Leary MC, Saver JL: Annual incidence of first silent stroke in the United States: a preliminary estimate. Cerebrovasc Dis 16:280-285, 2003. 17. Lee LK, Bateman BT, Wang S, Schumacher HC, Pile-Spellman J, Saposnik G: Trends in the hospitalization of ischemic stroke in the United States, 1998-2007. Int J Stroke 7:195-201, 2012. 18. Leung SS, Lee WT, Lui SS, Ng MY, Peng XH, Luo HY, Lam CW, Davies DD: Fat intake in Hong Kong Chinese children. J Am Clin Nutr 72: 1373S-1378S, 2000. 19. Lindekleiv H, Sandvei MS, Njolstad I, Lochen ML, Romundstad PR, Vatten L, Ingebrigtsen T, Vik A, Mathiesen EB: Sex differences in risk factors for aneurysmal subarachnoid hemorrhage. Neurology 76:637-643, 2011. 20. Lovelock CE, Rinkel GJ, Rothwell PM: Time trend in outcome of subarachnoid hemorrhage. Neurology 74:1494-1501, 2010.

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21. Nieuwkamp DJ, Setz LE, Algra A, Linn FH, de Rooij NK, Rinkel GJ: Changes in case fatality of aneurysmal subarachnoid haemorrhage over time, according to age, sex, and region: a meta-analysis. Lancet Neurol 8:635-642, 2009. 22. Population and vital events statistics in Hong Kong e Births, deaths, marriages, domestic house. Census and Statistics Department, the Government of the Hong Kong Special Administrative Region. Available at: http://www.censtatd.gov.hk/hong_ kong_statistics/statistics_by_subject/index.jsp. Accessed June 11, 2012. 23. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, Redgrave JN, Bull LM, Welch SJ, Cuthberton FC, Binney LE, Gutnikov SA, Anslow P, Banning AP, Mant D, Mehta Z: Oxford Vascular Study: Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study). Lancet 366: 1773-1783, 2005. 24. Sekikawa A, Hayakawa T: Prevalence of hypertension, its awareness and control in adult population in Japan. J Human Hypertens 18:911-912, 2004. 25. Sudlow CL, Warlow CP: Comparing stroke incidence worldwide: what makes studies comparable? Stroke 27:550-558, 1996. 26. Tirschwell DL, Longstreth WT Jr: Validating administrative data in stroke research. Stroke 33: 2465-2470, 2002. 27. van Gijn J, Kerr RS, Rinkel GJ: Subarachnoid haemorrhage. Lancet 369:306-318, 2007. 28. Vlak MH, Rinkel GJ, Greebe P, Algra A: Independent risk factors for intracranial aneurysms and their joint effect. A case control study. Stroke 44:984-987, 2013. 29. Vlak MH, Rinkel GJ, Greebe P, Greving JP, Algra A: Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification. J Neurol Neurosurg Psychiatry 84:619-623, 2013. 30. Wall Street Journal. Japanese Smoker: Going the way of the dodo? Available at: blogs.wsj.com/ japanrealtime/2011/10/13/Japanese-smoker-goingthe-way-of-the-dodo. Accessed March 11, 2013. 31. Wong GK, Lam S, Ngai K, Wong A, Mok V, Poon WS: Cognitive Dysfunction after Aneurysmal Subarachnoid Haemorrhage Investigators: Evaluation of cognitive impairment by the Montreal cognitive assessment in patients with aneurysmal subarachnoid haemorrhage: prevalence, risk factors and correlations with 3 month outcomes. J Neurol Neurosurg Psychiatry 83:1112-1117, 2012. 32. Wong GK, Ng RY, Poon WS: Aneurysmal subarachnoid haemorrhage. Surgical Practice 12: 51-55, 2008. 33. Wong GK, Poon WS, Boet R, Chan MT, Gin T, Ng SC, Zee BC: Health-related quality of life after aneurysmal subarachnoid hemorrhage: profile and clinical factors. Neurosurgery 68:1556-1561, 2011. 34. Wong GK, Wong R, Mok VC, Fan DS, Leung G, Wong A, Chan AS, Zhu CX, Poon WS: Clinical

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study on cognitive dysfunction after spontaneous subarachnoid haemorrhage: patient profiles and relationship to cholinergic dysfunction. Acta Neurochir (Wien) 151:1601-1607, 2009.

TUMOR

35. Woodworth GF, Biard CJ, Garces-Ambrossi G, Tornascia J, Tamargo RJ: Inaccuracy of the administrative database: comparative analysis of two databases for the diagnosis and treatment of intracranial aneurysms. Neurosurgery 65:251-256, 2009. 36. Yasuno K, Bilguvar K, Bijlenga P, Low SK, Krischek B, Auburger G, Simon M, Krex D, Arlier Z, Nayak N, Ruigrok YM, Niemela M, Tajima A, von und zu Fraunberg M, Doczi T, Wirjatijasa F, Hata A, Blasco J, Oszvald A, Kasuya H, Zilani G, Schoch B, Singh P, Stuer C, Risselada R, Beck J, Sola T, Ricciardi F, Aromaa A, Illig T, Schreiber S, van Duijn CM, van

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Conflict of interest statement: This study was supported by the Neurosurgery Research and Training Fund, the Chinese University of Hong Kong. Received 26 October 2012; accepted 27 July 2013; published online 22 September 2013 Citation: World Neurosurg. (2014) 81, 3/4:552-556. http://dx.doi.org/10.1016/j.wneu.2013.07.128 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.

Intracranial Hemangiopericytoma—Our Experience in 30 Years: A Series of 43 Cases and Review of the Literature Angelina Graziella Melone1, Alessandro D’Elia1, Francesca Santoro2, Maurizio Salvati3, Roberto Delfini1, Giampaolo Cantore3, Antonio Santoro1

Key words Hemangiopericytoma - Intracranial - Recurrence - Survival - Treatment -

Abbreviations and Acronyms EBRT: External beam radiotherapy GTR: Gross total resection HPC: Hemangiopericytoma OS: Overall survival STR: Subtotal resection WHO: World Health Organization From the Departments of 1Neurosurgery and 2 Neuroradiology, Sapienza University of Rome; and the 3Department of Neurosurgery INM—IRCCS Neuromed, Pozzilli (Isernia), Sapienza University of Rome, Rome, Italy To whom correspondence should be addressed: Angelina Graziella Melone, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2014) 81, 3/4:556-562. http://dx.doi.org/10.1016/j.wneu.2013.11.009 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2014 Elsevier Inc. All rights reserved.

INTRODUCTION

- OBJECTIVE:

Meningeal hemangiopericytoma (HPC) is a rare, aggressive central nervous system tumor that tends to invade locally and to metastasize, and has a high rate of recurrence.

- METHODS:

This study presents a retrospective review of patients managed for intracranial HPC at Rome University Hospital.

- RESULTS:

A total of 43 patients with intracranial HPC were treated from 1980 to 2010. Treatment and follow-up information was available for analysis on 36 patients. The median survival for all patients was 83.5 months after date of diagnosis, with 1-year, 5-year, and 10-year survival rates of 100%, 94.4%, and 72.2%, respectively. Eighteen patients (41.86%) had HPC recurrence. The median time until recurrence was 72.24 months, with 1-year, 5-year, and 10-year progression-free survival rates of 98%, 51%, and 29%, respectively. Five patients (11.62%) developed extracranial metastasis. Patients undergoing any form of adjuvant radiation treatment, including external beam radiotherapy, Gamma Knife radiosurgery, and/or proton beam therapy, had no longer median overall survival (OS) (178 vs. 154 months, respectively; P [ .2); but did have a significantly improved recurrence-free interval (108 vs. 64 months; P [ .04) compared with patients who did not undergo radiation treatment. Tumor characteristics associated with earlier recurrence included size ‡7 cm (log-rank, P < .05) and sinus invasion (log-rank, P < .05).

- CONCLUSIONS:

Strategies combining adjuvant radiation with tumor resection seemed to hinder tumor progression, but had no effect on OS or the development of metastases. Greater extent of resection was associated with increased OS (log-rank, P < .05). Anaplastic HPC was associated with reduced OS and with reduced recurrence interval (log-rank, P < .05).

Intracranial hemangiopericytoma (HPC) is a rare, vascularized mesenchymal tumor. It develops from malignant transformation

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WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2013.11.009