Influence of advanced age on postoperative outcomes and total loss following breast reconstruction: a critical assessment of 560 cases

Objective: to evaluate the role of age in the risk of postoperative complications in patients submitted to unilateral breast reconstruction after mastectomy, with emphasis on total reconstruction loss. Methods: we conducted a retrospective study of patients submitted to breast reconstruction, whose variables included: oncological and reconstruction data, postoperative complications, including loss of reconstruction and complications of surgical wound. We divided the patients into two groups, according to the classification of the Brazilian National Elderly Policy and the Statute of the Elderly: young (age <60 years) and elderly (60 years or more). We also grouped them according to the World Health Organization classification: young people (age <44 years), middle age (45-59 years); elderly (age 60-89 years) and extreme advanced age (90 years or older). We applied the surgical risk classification of the American Society of Anesthesiologists to investigate the role of the preoperative physical state as a possible predictor of complications. Results: of the 560 patients operated on, 94 (16.8%) were Matsumoto Influência da idade avançada sobre a evolução pós-operatória e a perda total da reconstrução mamária 8 Rev Col Bras Cir 2018; 45(2):e1616 REFERÊNCIAS 1. McKenna RJ Sr, Greene T, Hang-Fu LC, Hayes DF, Scanlon EF, Schweitzer RJ, et al. Implications for clinical management in patients with breast cancer. Long-term effects of reconstruction surgery. Cancer. 1991;68(5 Suppl):1182-3. 2. Lu SM, Nelson JA, Fischer JP, Fosnot J, Goldstein J, Selber JC, et al. The impact of complications on function, health, and satisfaction following abdominally based autologous breast reconstruction: a prospective evaluation. J Plast Reconstr Aesthet Surg. 2014;67(5):682-92. 3. Munhoz AM, Montag E, Filassi JR, Gemperli R. Immediate nipple-areola-sparing mastectomy reconstruction: an update on oncological and reconstruction techniques. World J Clin Oncol. 2014;5(3):478-94. 4. Anderson GF, Hussey PS. Population aging: a comparison among industrialized countries. Health Aff (Millwood). 2000;19(3):191-203. 5. Ramos LR, Veras RP, Kalache A. Envelhecimento populacional: uma realidade brasileira. Rev Saúde Pública. 1987;21(3):211-24. 6. Ogunbiyi SO, Lee S, Mathew J, Cheung KL. Primary breast cancer in the elderly: a systematic literature review on histological type and clinical outcome. Future Oncol. 2015;11(2):259-65. 7. Chang EI, Vaca L, DaLio AL, Festekjian JH, Crisera CA. Assessment of advanced age as a risk factor in microvascular breast reconstruction. Ann Plast Surg. 2011;67(3):255-9. 8. Girotto JA, Schreiber J, Nahabedian MY. Breast reconstruction in the elderly: preserving excellent quality of life. Ann Plast Surg. 2003;50(6):572-8. 9. Yanquez FJ, Clements JM, Grauf D, Merchant AM. Synergistic effect of age and body mass index on mortality and morbidity in general surgery. J Surg Res. 2013;184(1):89-100. 10. Gajdos C, Kile D, Hawn MT, Finlayson E, Henderson WG, Robinson TN. Advancing age and 30-day adverse outcomes after nonemergent general surgeries. J Am Geriatrics Soc. 2013;61(9):1608-14. 11. Butz DR, Lapin B, Yao K, Wang E, Song DH, Johnson D, et al. Advanced age is a predictor of 30-day complications after autologous but not implantbased postmastectomy breast reconstruction. Plast Reconstr Surg. 2015;135(2):253e-61e. 12. Lipa JE, Youssef AA, Kuerer HM, Robb GL, Chang DW. Breast reconstruction in older women: advantages of autogenous tissue. Plast Reconstr Surg. 2003;111(3): 1110-21. 13. Selber JC, Burgey M, Sonned SS, Kovach S, Wu L, Serletti JM. Free flap breast reconstruction in advanced age: is it safe? Plast Reconstr Surg. 2009;124(4):1015-22. 14. Küchemann BA. Envelhecimento populacional, cuidado e cidadania: velhos dilemas e novos desafios. Soc. Estado. 2012;27(1):165-80. 15. Ahmad OB, Boschi-Pinto C, Lopez AD, Murray CJ, Lozano R, Inoue M. Age Standardization of Rates: a new WHO standard [Internet]. Geneva: World Health Organization; 2001[cited 2017 Feb 10]. Available from: http://www.who.int/healthinfo/ paper31.pdf 16. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, Edwards BK, editors. SEER Cancer Statistics Review, 1973-1998. Bethesda: National Cancer Institute. 2001 – [cited 2017 Feb 10]. Available from: https://seer.cancer.gov/archive/ csr/1973_1998. 17. Berger NA, Savvides P, Koroukian SM, Kahana EF, Deimling GT, Rose JH, et al. Cancer in the elderly. Trans Am Clin Climatol Assoc. 2006;117:147-55; 60 years of age or older. We observed a local complication rate of 49.8%, the majority being self-limited. The incidences of necrosis, infection and dehiscence were 15.5%, 10.9% and 9.3%, respectively. Patients older than 60 years presented a chance of complication 1.606 times greater than the younger ones. Forty-five (8%) patients had loss of the reconstruction; there was no statistically significant difference in the mean age of the patients who presented this result or not (p=0.321). Conclusion: in selected patients, breast reconstruction can be considered safe; most documented complications were limited and could be treated conservatively.


INTRODUCTION
B reast reconstruction is a well established procedure and is considered the standard treatment for patients with breast cancer who wish to repair the oncologic defect 1 .The choice of the reconstruction technique depends on the individual characteristics of each patient and is also influenced by the analysis of the surgical risk profile by the plastic surgeon 2,3 .Data from the Brazilian Institute of Geography and Statistics (IBGE) show that the elderly population is the one with the highest growth rates in Brazil, and similar demographic patterns can be found in other countries 4,5 .At the same time, the incidence of breast cancer increases with age, with 50% of cases occurring in women over 65 years of age 6 .The technological advances in medical treatment, among other factors, led to an increase in life expectancy, suggesting that the elderly population will require an increasing number of surgical procedures 7 .With advancing age, the decrease in the efficiency of the healing process and the reduction of cardiovascular function may represent an increase in the perioperative risk of this subgroup of cancer patients [7][8][9] .In addition, advanced age is often referred to as an independent risk factor for complications in general surgery patients 9,10.However, few studies have evaluated the influence of age on the complications rates and on the disadvantages and benefits of breast reconstruction 7,8,[11][12][13] .Some clinical series that evaluated the impact of age on complications in specific reconstruction techniques demonstrated greater clinical and surgical morbidity [11][12][13] .
Considering that data on breast reconstruction in the Brazilian elderly population are limited, this study sought to investigate the postoperative complications in this specific patients' group.The main objective of the study was to globally quantify the effect of age on postoperative complications.We also sought to investigate the relationship between age and total loss of the breast reconstruction.

METHODS
We carried out a retrospective cohort that identified all patients submitted to unilateral breast reconstruction at the Cancer Institute of the State of São Paulo (ICESP) and at the Sírio-Libanês Hospital (HSL).
We conducted this study in accordance with the ethical We compared demographic and comorbidity data between age groups based on the NEP and WHO classifications.As the oldest patient in the sample was 88 years old, we grouped all patients older than 60 years for statistical analysis.To compare the continuous variables for the occurrence of complications (yes or no) or by any other categorical variable with two categories, we used the Student's t-test.To compare the continuous variables with more than two categories, we used the analysis of variance (ANOVA) model.To compare the categorical variables for the occurrence of complications (yes or no) or by any other categorical variable with two or more categories, we used the chi -square test.We used the Fisher's exact test or the Likelihood Ratio when necessary.We also used the simple logistic regression model to verify which variables, individually, related to the occurrence of complications, to obtain the Odds Ratio (OR) for the occurrence of the mentioned outcomes for each variable.After the logistic regression analysis for each clinical risk factor and for the complications, we conducted a multivariate logistic regression analysis.However, some of the variables were significantly correlated with the others, and it was not possible to include all variables in the same model.Therefore, we chose to construct new variables with the combination of variables considered as risk factors.The new variables, combined two to two, were part of a simple logistic regression model.The value of p=0.05 was considered statistically significant.We used the SPSS software for Windows 7.0 (SPSS Inc.Chicago, Illinois) for all statistical analysis.

RESULTS
We analyzed the medical records of 560 consecutive patients (ages between 23

DISCUSSION
Advanced age is recognized as a risk factor for cancer, and 60% of new cases are diagnosed in pa-tients over 60 years 16,17 .Moreover, the increase in life expectancy has increased the number of elderly patients who require surgeries for oncologic resections and reconstructions 18 .Despite the evolution of breast cancer treatment and the aging process of the female population, treatment protocols in the elderly population are still based on studies with limited levels of evidence 19 .
Due to the scarcity of studies with sufficient evidence to define the risks and benefits for this population segment, elderly patients tend to receive incomplete treatment for breast cancer 19,20 .In fact, some studies have shown discrepancies in relation to breast reconstruction rates in the different age groups, and only a minority of the elderly patients with breast neoplasia choose to undergo reconstruction 21 .
Another important point is the controversy in establishing the age limits between the different age groups and the lack of uniformity in the definition of the term elderly.Some studies used the age of 50 as a reference 22 , while others used 55 years 23 , 60 24 , or 65 years 25 .
In the present study, we defined the age of 60 years as the limit between young and old, as recommended by the Brazilian National Elderly Policy 14 .This classification proved useful and clinically relevant, since the great reduction in breast reconstruction rates is observed after the fifth and sixth decades of life.We also used the WHO classification to include an international categorization usually employed in public health worldwide 15 .
In breast reconstruction, it is essential to determine the anthropometric and clinical factors associated with higher complication rates [25][26][27] .Age 13,23 , smoking 22,25,28 , obesity 22,23,25,27,28 , SAH 24,25,27 and DM 24 are frequently mentioned as potential risk factors.In this scenario, there is no consensus regarding the role of age on complications in patients with breast neoplasms undergoing reconstruction [13][14][15][16][17] .In this sample, patients with DM had a significantly higher mean age than nondiabetics, and there was also a significant relationship between age and SAH.Similarly, the mean age for ASA 1 patients was significantly lower than for patients classified as ASA 2 or 3. We found no significant relationship between smoking and obesity in elderly patients.Despite this, considering the WHO classification, we observed a greater percentage of young patients in the non-smokers group in relation to smokers and former smokers.
Regarding breast reconstruction, some studies have compared the rates of complications among young and old patients 7,8,[11][12][13] .In this study, the comparison of complication rates among age groups according to NEP classification showed a higher incidence of complications in the advanced age group, although this difference occurred at the limit of significance (p=0.05).When we used WHO classification, we observed a significantly higher incidence of complications in the elderly/extremely old.Moreover, the overall rate of surgical complications in young and old patients was 47.8% and 59.6%, respectively, higher than those reported in other published series 7,8,[11][12][13]29 . Thi is due to the inclusion of minor complications, such as mild to moderate seromas, which exhibited a total incidence of 22% and accounted for almost 45% of all complications.In spite of the high incidence of seromas when compared to other studies, we must be emphasize some points.Some studies with large samples are based on the American College of Surgeons National Surgical Quality Improvement Program (ACS -NSQIP), which does not include some adverse events (such as seroma) in the list of complications 22,23 .Thus, if the seroma were excluded from the list of complications in this study, the results would become comparable to previously published clinical series 7,8,[11][12][13] .
Considering all types of adverse events, there was no significant difference in the mean age among patients who presented complications.In addition, the comparison of young and elderly patients did not show a significant difference in the isolated incidence of each type of complication, with the exception of hematoma.
And although there is no consensus to characterize age as a risk factor for breast reconstruction, some studies have demonstrated ASA classification as a predictor for perioperative complications 7,30 .In this series, patients classified as ASA 2 or 3 accounted for almost 70% of the entire sample.In contrast to observations from other studies 7,30 , the ASA classification did not demonstrate a significant correlation with the incidence of complications.
At this point, we believe that this aspect should not contraindicate reconstruction, although one should take additional care in patients with a higher surgical risk.
Despite the higher rates of complications in the present study, the total loss of reconstruction was less frequent than in other series with lower global rates of adverse events 12,29 .Furthermore, it is important to note that, although the complication rate was higher in elderly patients, this difference did not result in a higher incidence of total reconstruction loss.On the other hand, other studies have observed that age greater than 5022 and 55 years 23 were independent predictive factors for reconstruction loss.In a paradoxal way, the incidence of reconstruction loss was lower in patients who had presented seroma and necrosis than in patients who did not present such outcomes.One hypothesis to explain this finding is that the diagnosis of these two events motiva- Other limitations of the present study require attention.First, we collected the data prospectively but evaluated them retrospectively.In addition, the study was observational and non-randomized.There is, there-fore, a selection bias that cannot be excluded.Although the sample size of this series is significant, the notable low incidence of some types of complication and some reconstruction modalities may have prevented the analysis from achieving the desired statistical power.In addition, we could not perform comparisons of the results in patients with extreme old age, smoking and diabetics, as well as subgroups of different surgical techniques, so that the clinical relevance of the type of breast reconstruction in these groups remains controversial.Prospective studies will be needed to clarify this issue and to define which operative techniques are most appropriate for elderly patients.Second, questions about quality of life and the analysis of treatment costs were not part of the objectives of this study, but will be relevant to future research.Finally, although the postoperative complications reported by the medical team may be criticized for possible underreporting, the data in the present study reflect the unique experience of a single team in a tertiary hospital dedicated to the Brazilian population.
We conclude that breast reconstruction is a valid option for adequately selected patients.This study showed that age is an independent risk factor for surgical complications, although the vast majority of these complications have been limited and could be treated conservatively.However, patients who are candidates for immediate reconstruction should be advised that age will not necessarily imply a greater risk of loss of reconstruction.Thus, it is appropriate to indicate breast reconstruction in elderly patients and this procedure should be considered in counseling patients under treatment for breast cancer.

R E S U M O
guidelines of the Declaration of Helsinki, and it was approved by the Ethics and Research Committees of the respective institutions (approval protocols 474/13 and 714.543).We analyzed the database of each institution (ICESP/HSL) for information on clinical complications associated with breast reconstruction.We excluded patients with incomplete information.The variables included were: oncological data, reconstruction data (technique), postoperative complications, including loss of reconstruction, surgical wound complications (reconstruction site and donor area), early infection (during hospitalization for reconstruction), late infection, seroma, dehiscence, hematoma.We divided the patients according to the classification of the Brazilian National Elderly Policy and the Statute of the Elderly (NEP) 14 in two groups: young people (age <60 years) and elderly (60 years or more).We also divided them into groups according to the World Health Organization (WHO) classification 15 : group I, young people (age <44 years); group II, middle age (age 45-59 years); group III, elderly (age 60-89 years), and group IV, extreme old age (90 years or more).We applied the American Society of Anesthesiologists (ASA) classification to investigate the role of preoperative physical status as a possible predictor of complications: Class 1 (healthy patient), Class 2 (mild or moderate systemic disease), Class 3 (severe systemic disease), Class 4 (severe systemic disease with constant risk of life), and Class 5 (patient to die within 24 hours despite surgical treatment).
ted a rapid treatment by the medical team with intensive follow-up, re-hospitalization, drainage of collections, debridement of devitalized tissues and antibiotic therapy, which resulted, in the end, in lower reconstruction loss rates when compared to patients with subclinical infections.Regarding reconstruction techniques, almost 50% of the patients underwent reconstruction with alloplastic materials, 27% with autogenous tissues and 24% with a combination of alloplastics and autogenous tissues.Both young and elderly patients underwent alloplastic reconstruction more frequently.Like other authors, we did not find a correlation between age and the incidence of complications when performing the analysis of the alloplastic, autogenous and alloplastic / autogenous groups separately7,13,22,23,25,31 .One of the obvious limitations of this study is the relatively small sample size in each subgroup of reconstruction technique.Future studies with a larger number of patients may reveal whether current findings are due to inadequate sample size or are a valid consideration.

Table 1 .
Distribution of reconstruction techniques by age groups.
NEP: National Policy for the Elderly and the Elderly Statute; WHO: World Health Organization.of94),reconstructionwithalloplasticmaterialswas the most common reconstruction modality.Table1shows the distribution of reconstruction techniques in the different age groups.The comparison of the different age groups (NEP and WHO classifications) showed no relation between age and Body Mass Index (BMI, p=0.217).Patients with diabetes mellitus (DM) had a significantly higher mean age (58 years) than non-diabetic ones (49.4 years, p<0.001).Advanced age was an independent risk factor for DM (OR 4.57, p<0.001).Similarly, we found a significant relationship between age and systemic arterial hypertension (SAH, p<0.001).The comparison between non-hypertensive and hypertensive patients showed a significant increase in the proportion of elderly patients in the second group (p<0.001).Among the elderly patients, 71 (75.5%) were non-smokers, 14 (14.9%) were former smokers and nine (9.6%) were smokers.In relation to smoking, the groups of young and old (NEP classification) were statistically similar (p=0.408).However, considering the WHO classification, there was a significant difference (p=0.007), with a higher percentage of young patients in the nonsmoking contingent compared to smokers and former smokers.ASA 1 patients represented 30.7% (172/560) of the sample, while those ASA 2 and 3 accounted for 69.3%.No patient had an ASA 4 or 5 status (Table2).

Table 2 .
Distribution of Comorbidities by age groups.
SD: standard deviation; SAH: Systemic Arterial Hypertension; DM: Diabetes Mellitus; NEP: National Policy for the Elderly and the Elderly Statute; WHO: World Health Organization; BMI: body mass index.Patients who did not present complications had a mean age of 48.8 years, while the mean age of those who presented them was 51.4 years (Table3).risk of complications without DM.Elderly and diabetic patients presented a 2.67-fold greater risk of complication than non-diabetic young women (p=0.048).We observed a significant increase in complication rates in the advanced age groups (p=0.015)(Table3); each one-year increment corresponded to a 2.4% increase in the risk of complications, as demonstrated by the logistic regression analysis.The same analysis showed that the elderly/ construction was statistically equivalent in both groups (p=0.974).Likewise, there was no significant difference in the incidence of this complication among the young, middle-aged and elderly/extremely old age groups (p=0.405).

Table 3 .
Distribution of age groups with averages, standard deviations, medians and range in the groups with and without complications and with or without total loss of reconstruction.
SD = standard deviation; NEP: National Policy for the Elderly and the Elderly Statute; WHO: World Health Organization.

Table 4 .
Correlation of risk factors versus age groups and complications (singly, one by one, and two by two).Results of the logistic regression analysis.BMI: body mass index; DM: Diabetes Mellitus; OR: odds ratio; CI: confidence interval.