Trend assesment by comparison with a Cancer Registry
Paolo Contiero, National Cancer Institute of Milan
5 July 2009
I have carefully read the paper, interesting because present a method to estimates breast cancer incidence, a so important topic for health service planning and primary prevention researches. In my opinion, the weakness of this paper is the lack of a gold standard by which validate the method and its results. This could lead to the introduction of some bias in the estimates that are not possible to detect easily. By this notes I show some data from the Cancer Registry of Varese and the hospital discharges of the same area. The Cancer Registry of Varese began its activity in 1976 and its data was included in the last four editions of the Cancer Incidence in Five Continents. The Cancer Registry data are linked with the hospital discharge (SDO), pathology report and death certificate files, all of these sources contain personal data. The availability of the hospital discharge file gave me the possibility to evaluate the algorithm proposed versus a gold standard such as a Cancer Registry. A Cancer Registry could be considered a gold standard because: i) it contains validated data, i.e. true cases and not false positives or not accurate diagnosis ii) it contains virtually all the cases of the target population, without selection related to diagnosis or treatment, as could be using surgical procedure to identify cases iii) it register personal data, avoiding the bias of counting twice or more patients with more that one SDO iv) it can correctly classify incident and prevalent cases.
The comparison considers four years of incidence, from 2000 to 2003. I have applied the algorithm by Giordano to the SDO of the residents of Varese province, from 1/1/2000 to 31/12/2003. I have linked those records with the Varese Cancer Registry. The number of cases registered by the Registry, from year 2000 to 2003 are respectively: 721 , 729 , 731 , 739, with an increase in 2003 vs 2000 of 2.5 %. The algorithm identifies for the same years the following cases (% of lost cases): 653 (-9.4 %) , 674 (-7.5 %), 714 (-2.3 %), 704 (-4.7 %), with an increase in 2003 vs 2000 of + 7.8 % The cases discarded by the registry and identified by the algorithm (390) were prevalent cases or cases with a diagnosis different from malignant neoplasm of breast. The cases not caught by the algorithm but identified by the Registry (565) were cases that have on the hospital discharges a diagnosis different from malignant neoplasm of breast or cases with none or different surgical procedures respect to those used by the algorithm.
Conclusion
The algorithm described in the paper produce an underestimate of the real number of cases that varies from 4.7 to 9.4 %. This is the result of two bias that act in two different directions. Prevalent cases inflates incidence meanwhile cases excluded by the algorithm for diagnostic or intervention codes produce a bias in the opposite direction. The increase in the number of cases computed by the algorithm on the hospital discharges is 2.6 % per year on Varese data, similar to the data reported in table 4 of the paper by Giordano, meanwhile the Varese Cancer Registry reports an increase per year of 0.8 %. By this comparison, it seems the increase computed by the algorithm doesn’t correspond to a real increase in the number of cases but that it depends only by the increasing use of surgical procedures.
Competing interests
I have no competing interest
INCIDENCE OF BREAST CANCER IN ITALY: WHY HOSPITALIZATION RECORDS ARE A VALUABLE OPPORTUNITY
Prisco Piscitelli, CROM
20 July 2009
Although Cancer Registries remain the gold standard for epidemiologic evaluation of tumors, unfortunately they are not currently available in all Italian provinces. Therefore, in order to evaluate the incidence of neoplastic lesions at national level (as declared in its publications), the Italian Association of Cancer Registries must use other data sources (such as mortality rates provided by the National Instiute for Statistics, ISTAT) or refer to average values determined within the few existing registries (actually 70% of Italian population is not being covered by cancer registries). This means that national data concerning the incidence of cancers in Italy are the result of average estimations or statistical models and do not reflect a real "count" of overall cases. On the other hand, there is a huge National database which is available for researchers: the National hospitalization records database (SDO), which has already been validated in many internation publications, being also uses by Piemonte Region in its cancer surveillance programs (with good published results).
Therefore, authors of the article tried to use the National hospitalization database (SDO) as a potential datasource for determining the incidence of such an impactful tumour as breast cancer.
Concerning the SDO database, it must be pointed out that authors have excluded 1999 from the analysis because the Ministry of Health - at our knowledge - can provide complete archives since year 2000. However, if some hospital records would have not been sent to the central database, this could have produced only an underestimation and not an overestimation of the phenomenon.
While examining SDO database, authors DID NOT analyzed "diagnosis of breast cancer" because it would have produced too many bias due to the double count of the same patients hospitalized twice or more times with the same "major diagnosis". Authors have rather decided to analyze the number of surgical interventions, namely quadrantectomies and mastectomies in order to "count" the new breast cancer cases because:
- these procedures are used only in case of breast cancer;
- the risk of "double count" of the same patient is low because number of patients who undergo mastectomy or quadrantectomy twince in the same year is very very low, as assessed in a preliminary survey by the surgeons involved in the study;
- the risk of including prevalent cases in the "count" is also low because the time elapsing between new diagnosis of brest cancer and surgical intervention do not exceed 30 days according to the US and European guidelines; furthermore, relapses of the disease are mostly detected after 5 and even 10 years from the intervention (therefore outside of the range of the study period). If looking at the literature, the risk of relapses after mastectomy is 5-10% at 10 years, while the risk of relapses after quadrantectomy is 10-15% at 10 years; only breast relapsing leasions are eligible for new surgical procedures (actually metastases are treated in other ways), and only lesions relapsig after quadrantectomy are treated surgically with a new mastectomy.
On the other hand, even though authors have declared in methodological section the risk of a small overestimation of new breast cancer cases, the "count" provided in the article CANNOT consider all the breast cancers which are not treated by surgery (about 10% of new breast tumour diagnoses) and the small proportion of "in situ carcinomas" which are not treated with quadrantectomy but only with tumorectomy: so there is a wide underestimation preliminary effect to be taken into account, so that the surprising results of the study could be also regarded as conservative ! Furthermore, there's no risk of having included benign lesions because authors have counted MAJOR BREAST SURGICAL PROCEDURES (quadrantectomies and mastectomies) and have decided to exclude tumorectomies and excision biopsis from the analysis.
Concerning the comment of the colleague Paolo Contiero, who did a very good job in the right experimental perspective, it seems that he has analyzed SDO database of Varese province (where a cancer registry sortunately exists)looking for major diagnosis of breast cancer. On the contrary, authors of the article has examined only major breast surgical procedures, namely mastectomy (ICD9-CM code 85.4) and quadrantecomy (code 85.22), therefore resulting in an overestimation due to double count of the same patient. However, authors may also hypotize that data of Varese province could result in a small difference between the Cancer Registry and the SDO database (actually 2% as reported by Dr. Contiero), but the objective of the article was not to compare SDO database with Cancer Registries datasets, because there are no problem in assessing the phenomenon in those provinces where a Registry already exists. Authors' aim was actually to overcome the existimations produced when computing incidence at national level by the methods currently used (average calculations and statistical models based on ISTAT mortality rates). In this perspective, and until cancer registries will not cover all the Country, SDO database could be a valuable opportunity to be successfully used as already has been done in Piemonte Region.
1. Icks A., Haastert B., Becker C., Meyer G., Trend of hip fracture incidence in Germany 1995–2004: a population-based study Osteoporos Int (2008) 19:1139–1145.; 2. Maravic M., Le Bihan C., Landais P. Fardellone P., Incidence and cost of osteoporotic fractures in France during 2001. A methodological approach by the national hospital database, Osteoporos Int (2005) 16: 1475–1480; 3. Mann E., Icks A. Haastert B., Meyer G. (2009), Hip fracture incidence in the elderly in Austria: An epidemiological study covering the years 1994 to 2006, BMC Geriatr. 2008; 8: 35; 4. Caldarola P., Cuonzo M. et al. (2008), Epidemiology of heart failure in Apulia Region. G Ital Cardiol Vol 10: 135-139; 5. Pervez H, Bhargwa A, Parker MJ. (2003), Accuracy and reliability of the clinical indicators related to hip fractures. Injury,34:522–524; 6. Osteoporosis in the European Community: a call for action. International Osteoporosis Foundation, Lyon (2002); 7. Autier P, Haentjens P, Bentin J et al (2000), Costs induced by hip fractures: a prospective controlled study in Belgium. Belgian Hip Fracture Study Group. Osteoporosis Int 11:373–380; 8. Lippuner K, von Overbeck J, Perrelet R et al (1997), Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Osteoporos Int 7:414; 9. Dolan P, Torgerson DJ (1998) The cost of treating osteoporosis fractures in the United Kingdom female population. Osteoporos Int 8:611–617; 10. Johnell O, Gullberg B, Allander E, Kanis JA (1992) The apparent incidence of hip fracture in Europe: a study of national register sources. MEDOS Study Group. Osteoporos Int 2:298–302; 11. Vestergaard P, Rejnmark L, Mosekilde L. (2008), Strongly increasing incidence of hip fractures in Denmark from 1977 to 1999, Ugeskr Laeger, 170:621–623; 12. Hernandez JL, Olmos JM, Alonso MA, Gonzales-Fernandez CR, Martinez J, Pajaron M, Llorca J, Gonzales-Macias J. (2006), Trend in hip fracture epidemiology over a 14-year period In a Spanish population, Osteoporos Int. 17:464–470; 13. Lönnroos E, Kautianinen H, Karppi P, Huusko T, Kiviranta I, Sulkava R. (2006), Increased incidence of hip fractures. A population based-study in Finland. Bone, 39:623–627; 14. Bjorgul K, Reikeras O. (2007), Incidence of hip fracture in southeastern Norway. Int Orthop. 31:665–9; 15. Piscitelli P., Iolascon G., Giordano A.: Incidence and costs of hip fractures vs. hip arthritis: hospitalizations in Italy between 2000 and 2005, Osteoporosis International (2009) Suppl.12: P202; 16. Piscitelli P., Iolascon G.:Incidence and costs of hip fractures in Italy: 2000-2005 Clinical Cases in Bone Metabolism, vol. V (no. 3) – 2008; 17. Piscitelli P., Iolascon G.: Incidence and costs of hip fractures vs. acute myocardial infarction in the Italian population: a 4 years survey, Osteoporosis International (2007) 18: 211-219; . 18. Piscitelli P., Iolascon G.: Hip fractures in Italy, analysis of DRG data, Aging clinical and experimental research Vol. no.19 Suppl. to No.3, June 2007: 2-4; 19. Piscitelli P., Iolascon G., Guida G., Gimigliano R.: Incidence and costs of hip fractures vs. acute myocardial infarction in the population of Local Health Authorities ASL Lecce/1 and ASL Lecce/2: a 2 years survey, Italian Journal of Public Health, Year 4, Vol. 3, N.2 (2006): 75-77; 20. Piscitelli P., Guida G., Iolascon G.: Femoral fractures and orthopaedic surgery: a four years survey in Italy”, Journal of Orthopaedics and Traumatology (2005) 6: 203-206; 21. Piscitelli P., Guida G., Iolascon G.: Incidence and costs of hip fractures compared to acute myocardial infarction in the italian population: a 3 years study. Journal of Bone and Mineral Research, October 2004, Vol 19 Suppl., SU369). 22. van Dongen, JA, Voogd, AC, Fentiman, IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 Trial. J Natl Cancer Inst 2000; 92:1143. 23. Jacobson, JA, Danforth, DN, Cowan, KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med 1995; 332:907. 24. Arriagada, R, Le, MG, Rochard, F, Contesso, G. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol 1996; 14:1558. 25. Stefanik, D, Goldberg, R, Byrne, P, et al. Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1985; 3:660. 26. Schmoor, C, Sauerbrei, W, Bastert, G, Schumacher, M. Role of isolated locoregional recurrence of breast cancer: results of four prospective studies. J Clin Oncol 2000; 18:1696. 27. Buchanan, CL, Dorn, PL, Fey, J, et al. Locoregional recurrence after mastectomy: incidence and outcomes. J Am Coll Surg 2006; 203:469. 28. Jatoi, I, Tsimelzon, A, Weiss, H, et al. Hazard rates of recurrence following diagnosis of primary breast cancer. Breast Cancer Res Treat 2005; 89:173. 29. Veronesi, U, Saccozzi, R, Del Vecchio, M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med 1981; 305:6. 30. Kurtz, JM, Amalric, R, Brandone, H, et al. Local recurrence after breast-conserving surgery and radiotherapy. Frequency, time course, and prognosis. Cancer 1989; 63:1912. 31. Fisher, B, Costantino, J, Redmond, C, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993; 328:1581. 32. Fisher, B, Anderson, S, Redmond, CK, et al. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1995; 333:1456. 33. Wapnir, IL, Anderson, SJ, Mamounas, EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 2006; 24:2028. 34. van Tienhoven, G, Voogd, AC, Peterse, JL, et al. Prognosis after treatment for loco-regional recurrence after mastectomy or breast conserving therapy in two randomised trials (EORTC 10801 and DBCG-82TM). EORTC Breast Cancer Cooperative Group and the Danish Breast Cancer Cooperative Group. Eur J Cancer 1999; 35:32. 35. Haffty, BG, Carter, D, Flynn, SD, et al. Local recurrence versus new primary: clinical analysis of 82 breast relapses and potential applications for genetic fingerprinting. Int J Radiat Oncol Biol Phys 1993; 27:575. 36. Voogd, AC, van Oost, FJ, Rutgers, EJ, et al. Long-term prognosis of patients with local recurrence after conservative surgery and radiotherapy for early breast cancer. Eur J Cancer 2005; 41:2637. 37. Francis, M, Cakir, B, Ung, O, et al. Prognosis after breast recurrence following conservative surgery and radiotherapy in patients with node-negative breast cancer. Br J Surg 1999; 86:1556. 38. Dalberg, K, Mattsson, A, Sandelin, K, Rutqvist, LE. Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer. Breast Cancer Res Treat 1998; 49:69. 39. Pisansky, TM, Ingle, JN, Schaid, DJ, et al. Patterns of tumor relapse following mastectomy and adjuvant systemic therapy in patients with axillary lymph node-positive breast cancer. Impact of clinical, histopathologic, and flow cytometric factors. Cancer 1993; 72:1247. 40. Hsi, RA, Antell, A, Schultz, DJ, Solin, LJ. Radiation therapy for chest wall recurrence of breast cancer after mastectomy in a favorable subgroup of patients. Int J Radiat Oncol Biol Phys 1998; 42:495. 41. Dalberg, K, Mattsson, A, Sandelin, K, Rutqvist, LE. Outcome of treatment for ipsilateral breast tumor recurrence in early-stage breast cancer. Breast Cancer Res Treat 1998; 49:69. 42. Pisansky, TM, Ingle, JN, Schaid, DJ, et al. Patterns of tumor relapse following mastectomy and adjuvant systemic therapy in patients with axillary lymph node-positive breast cancer. Impact of clinical, histopathologic, and flow cytometric factors. Cancer 1993; 72:1247. 43. Hsi, RA, Antell, A, Schultz, DJ, Solin, LJ. Radiation therapy for chest wall recurrence of breast cancer after mastectomy in a favorable subgroup of patients. Int J Radiat Oncol Biol Phys 1998; 42:495. 44. Fourquet, A, Campana, F, Zafrani, B, et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys 1989; 17:719. 45. Chauvet, B, Reynaud-Bougnoux, A, Calais, G, et al. Prognostic significance of breast relapse after conservative treatment in node-negative early breast cancer. Int J Radiat Oncol Biol Phys 1990; 19:1125. 46. Fowble, B, Solin, LJ, Schultz, DJ, et al. Breast recurrence following conservative surgery and radiation: patterns of failure, prognosis, and pathologic findings from mastectomy specimens with implications for treatment. Int J Radiat Oncol Biol Phys 1990; 19:833. 47. Abner, AL, Recht, A, Eberlein, T, et al. Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer. J Clin Oncol 1993; 11:44.
Trend assesment by comparison with a Cancer Registry
5 July 2009
I have carefully read the paper, interesting because present a method to estimates breast cancer incidence, a so important topic for health service planning and primary prevention researches.
In my opinion, the weakness of this paper is the lack of a gold standard by which validate the method and its results. This could lead to the introduction of some bias in the estimates that are not possible to detect easily.
By this notes I show some data from the Cancer Registry of Varese and the hospital discharges of the same area.
The Cancer Registry of Varese began its activity in 1976 and its data was included in the last four editions of the Cancer Incidence in Five Continents.
The Cancer Registry data are linked with the hospital discharge (SDO), pathology report and death certificate files, all of these sources contain personal data.
The availability of the hospital discharge file gave me the possibility to evaluate the algorithm proposed versus a gold standard such as a Cancer Registry.
A Cancer Registry could be considered a gold standard because: i) it contains validated data, i.e. true cases and not false positives or not accurate diagnosis ii) it contains virtually all the cases of the target population, without selection related to diagnosis or treatment, as could be using surgical procedure to identify cases iii) it register personal data, avoiding the bias of counting twice or more patients with more that one SDO iv) it can correctly classify incident and prevalent cases.
The comparison considers four years of incidence, from 2000 to 2003.
I have applied the algorithm by Giordano to the SDO of the residents of Varese province, from 1/1/2000 to 31/12/2003.
I have linked those records with the Varese Cancer Registry.
The number of cases registered by the Registry, from year 2000 to 2003 are respectively:
721 , 729 , 731 , 739, with an increase in 2003 vs 2000 of 2.5 %. The algorithm identifies for the same years the following cases (% of lost cases): 653 (-9.4 %) , 674 (-7.5 %), 714 (-2.3 %), 704 (-4.7 %), with an increase in 2003 vs 2000 of + 7.8 %
The cases discarded by the registry and identified by the algorithm (390) were prevalent cases or cases with a diagnosis different from malignant neoplasm of breast. The cases not caught by the algorithm but identified by the Registry (565) were cases that have on the hospital discharges a diagnosis different from malignant neoplasm of breast or cases with none or different surgical procedures respect to those used by the algorithm.
Conclusion
The algorithm described in the paper produce an underestimate of the real number of cases that varies from 4.7 to 9.4 %. This is the result of two bias that act in two different directions. Prevalent cases inflates incidence meanwhile cases excluded by the algorithm for diagnostic or intervention codes produce a bias in the opposite direction.
The increase in the number of cases computed by the algorithm on the hospital discharges is 2.6 % per year on Varese data, similar to the data reported in table 4 of the paper by Giordano, meanwhile the Varese Cancer Registry reports an increase per year of 0.8 %.
By this comparison, it seems the increase computed by the algorithm doesn’t correspond to a real increase in the number of cases but that it depends only by the increasing use of surgical procedures.
Competing interests
I have no competing interest
INCIDENCE OF BREAST CANCER IN ITALY: WHY HOSPITALIZATION RECORDS ARE A VALUABLE OPPORTUNITY
20 July 2009
Although Cancer Registries remain the gold standard for epidemiologic evaluation of tumors, unfortunately they are not currently available in all Italian provinces. Therefore, in order to evaluate the incidence of neoplastic lesions at national level (as declared in its publications), the Italian Association of Cancer Registries must use other data sources (such as mortality rates provided by the National Instiute for Statistics, ISTAT) or refer to average values determined within the few existing registries (actually 70% of Italian population is not being covered by cancer registries). This means that national data concerning the incidence of cancers in Italy are the result of average estimations or statistical models and do not reflect a real "count" of overall cases. On the other hand, there is a huge National database which is available for researchers: the National hospitalization records database (SDO), which has already been validated in many internation publications, being also uses by Piemonte Region in its cancer surveillance programs (with good published results).
Therefore, authors of the article tried to use the National hospitalization database (SDO) as a potential datasource for determining the incidence of such an impactful tumour as breast cancer.
Concerning the SDO database, it must be pointed out that authors have excluded 1999 from the analysis because the Ministry of Health - at our knowledge - can provide complete archives since year 2000. However, if some hospital records would have not been sent to the central database, this could have produced only an underestimation and not an overestimation of the phenomenon.
While examining SDO database, authors DID NOT analyzed "diagnosis of breast cancer" because it would have produced too many bias due to the double count of the same patients hospitalized twice or more times with the same "major diagnosis". Authors have rather decided to analyze the number of surgical interventions, namely quadrantectomies and mastectomies in order to "count" the new breast cancer cases because:
- these procedures are used only in case of breast cancer;
- the risk of "double count" of the same patient is low because number of patients who undergo mastectomy or quadrantectomy twince in the same year is very very low, as assessed in a preliminary survey by the surgeons involved in the study;
- the risk of including prevalent cases in the "count" is also low because the time elapsing between new diagnosis of brest cancer and surgical intervention do not exceed 30 days according to the US and European guidelines; furthermore, relapses of the disease are mostly detected after 5 and even 10 years from the intervention (therefore outside of the range of the study period). If looking at the literature, the risk of relapses after mastectomy is 5-10% at 10 years, while the risk of relapses after quadrantectomy is 10-15% at 10 years; only breast relapsing leasions are eligible for new surgical procedures (actually metastases are treated in other ways), and only lesions relapsig after quadrantectomy are treated surgically with a new mastectomy.
On the other hand, even though authors have declared in methodological section the risk of a small overestimation of new breast cancer cases, the "count" provided in the article CANNOT consider all the breast cancers which are not treated by surgery (about 10% of new breast tumour diagnoses) and the small proportion of "in situ carcinomas" which are not treated with quadrantectomy but only with tumorectomy: so there is a wide underestimation preliminary effect to be taken into account, so that the surprising results of the study could be also regarded as conservative ! Furthermore, there's no risk of having included benign lesions because authors have counted MAJOR BREAST SURGICAL PROCEDURES (quadrantectomies and mastectomies) and have decided to exclude tumorectomies and excision biopsis from the analysis.
Concerning the comment of the colleague Paolo Contiero, who did a very good job in the right experimental perspective, it seems that he has analyzed SDO database of Varese province (where a cancer registry sortunately exists)looking for major diagnosis of breast cancer. On the contrary, authors of the article has examined only major breast surgical procedures, namely mastectomy (ICD9-CM code 85.4) and quadrantecomy (code 85.22), therefore resulting in an overestimation due to double count of the same patient. However, authors may also hypotize that data of Varese province could result in a small difference between the Cancer Registry and the SDO database (actually 2% as reported by Dr. Contiero), but the objective of the article was not to compare SDO database with Cancer Registries datasets, because there are no problem in assessing the phenomenon in those provinces where a Registry already exists.
Authors' aim was actually to overcome the existimations produced when computing incidence at national level by the methods currently used (average calculations and statistical models based on ISTAT mortality rates). In this perspective, and until cancer registries will not cover all the Country, SDO database could be a valuable opportunity to be successfully used as already has been done in Piemonte Region.
1. Icks A., Haastert B., Becker C., Meyer G., Trend of hip fracture incidence in Germany 1995–2004: a population-based study Osteoporos Int (2008) 19:1139–1145.;
2. Maravic M., Le Bihan C., Landais P. Fardellone P., Incidence and cost of osteoporotic fractures in France during 2001. A methodological approach by the national hospital database, Osteoporos Int (2005) 16: 1475–1480;
3. Mann E., Icks A. Haastert B., Meyer G. (2009), Hip fracture incidence in the elderly in Austria: An epidemiological study covering the years 1994 to 2006, BMC Geriatr. 2008; 8: 35;
4. Caldarola P., Cuonzo M. et al. (2008), Epidemiology of heart failure in Apulia Region. G Ital Cardiol Vol 10: 135-139;
5. Pervez H, Bhargwa A, Parker MJ. (2003), Accuracy and reliability of the clinical indicators related to hip fractures. Injury,34:522–524;
6. Osteoporosis in the European Community: a call for action. International Osteoporosis Foundation, Lyon (2002);
7. Autier P, Haentjens P, Bentin J et al (2000), Costs induced by hip fractures: a prospective controlled study in Belgium. Belgian Hip Fracture Study Group. Osteoporosis Int 11:373–380;
8. Lippuner K, von Overbeck J, Perrelet R et al (1997), Incidence and direct medical costs of hospitalizations due to osteoporotic fractures in Switzerland. Osteoporos Int 7:414;
9. Dolan P, Torgerson DJ (1998) The cost of treating osteoporosis fractures in the United Kingdom female population. Osteoporos Int 8:611–617;
10. Johnell O, Gullberg B, Allander E, Kanis JA (1992) The apparent incidence of hip fracture in Europe: a study of national register sources. MEDOS Study Group. Osteoporos Int 2:298–302;
11. Vestergaard P, Rejnmark L, Mosekilde L. (2008), Strongly increasing incidence of hip fractures in Denmark from 1977 to 1999, Ugeskr Laeger, 170:621–623;
12. Hernandez JL, Olmos JM, Alonso MA, Gonzales-Fernandez CR, Martinez J, Pajaron M, Llorca J, Gonzales-Macias J. (2006), Trend in hip fracture epidemiology over a 14-year period In a Spanish population, Osteoporos Int. 17:464–470;
13. Lönnroos E, Kautianinen H, Karppi P, Huusko T, Kiviranta I, Sulkava R. (2006), Increased incidence of hip fractures. A population based-study in Finland. Bone, 39:623–627;
14. Bjorgul K, Reikeras O. (2007), Incidence of hip fracture in southeastern Norway. Int Orthop. 31:665–9;
15. Piscitelli P., Iolascon G., Giordano A.: Incidence and costs of hip fractures vs. hip arthritis: hospitalizations in Italy between 2000 and 2005, Osteoporosis International (2009) Suppl.12: P202;
16. Piscitelli P., Iolascon G.:Incidence and costs of hip fractures in Italy: 2000-2005 Clinical Cases in Bone Metabolism, vol. V (no. 3) – 2008;
17. Piscitelli P., Iolascon G.: Incidence and costs of hip fractures vs. acute myocardial infarction in the Italian population: a 4 years survey, Osteoporosis International (2007) 18: 211-219; .
18. Piscitelli P., Iolascon G.: Hip fractures in Italy, analysis of DRG data, Aging clinical and experimental research Vol. no.19 Suppl. to No.3, June 2007: 2-4;
19. Piscitelli P., Iolascon G., Guida G., Gimigliano R.: Incidence and costs of hip fractures vs. acute myocardial infarction in the population of Local Health Authorities ASL Lecce/1 and ASL Lecce/2: a 2 years survey, Italian Journal of Public Health, Year 4, Vol. 3, N.2 (2006): 75-77;
20. Piscitelli P., Guida G., Iolascon G.: Femoral fractures and orthopaedic surgery: a four years survey in Italy”, Journal of Orthopaedics and Traumatology (2005) 6: 203-206;
21. Piscitelli P., Guida G., Iolascon G.: Incidence and costs of hip fractures compared to acute myocardial infarction in the italian population: a 3 years study. Journal of Bone and Mineral Research, October 2004, Vol 19 Suppl., SU369).
22. van Dongen, JA, Voogd, AC, Fentiman, IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 Trial. J Natl Cancer Inst 2000; 92:1143.
23. Jacobson, JA, Danforth, DN, Cowan, KH, et al. Ten-year results of a comparison of conservation with mastectomy in the treatment of stage I and II breast cancer. N Engl J Med 1995; 332:907.
24. Arriagada, R, Le, MG, Rochard, F, Contesso, G. Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy Breast Cancer Group. J Clin Oncol 1996; 14:1558.
25. Stefanik, D, Goldberg, R, Byrne, P, et al. Local-regional failure in patients treated with adjuvant chemotherapy for breast cancer. J Clin Oncol 1985; 3:660.
26. Schmoor, C, Sauerbrei, W, Bastert, G, Schumacher, M. Role of isolated locoregional recurrence of breast cancer: results of four prospective studies. J Clin Oncol 2000; 18:1696.
27. Buchanan, CL, Dorn, PL, Fey, J, et al. Locoregional recurrence after mastectomy: incidence and outcomes. J Am Coll Surg 2006; 203:469.
28. Jatoi, I, Tsimelzon, A, Weiss, H, et al. Hazard rates of recurrence following diagnosis of primary breast cancer. Breast Cancer Res Treat 2005; 89:173.
29. Veronesi, U, Saccozzi, R, Del Vecchio, M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med 1981; 305:6.
30. Kurtz, JM, Amalric, R, Brandone, H, et al. Local recurrence after breast-conserving surgery and radiotherapy. Frequency, time course, and prognosis. Cancer 1989; 63:1912.
31. Fisher, B, Costantino, J, Redmond, C, et al. Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer. N Engl J Med 1993; 328:1581.
32. Fisher, B, Anderson, S, Redmond, CK, et al. Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1995; 333:1456.
33. Wapnir, IL, Anderson, SJ, Mamounas, EP, et al. Prognosis after ipsilateral breast tumor recurrence and locoregional recurrences in five National Surgical Adjuvant Breast and Bowel Project node-positive adjuvant breast cancer trials. J Clin Oncol 2006; 24:2028.
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Competing interests
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