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The isolated local recurrence in a patient previously treated for early-stage invasive breast cancer presents a unique challenge to the oncologist. The clinical significance of an isolated local recurrence as a first event after treatment of early-stage invasive breast cancer, and its impact on survival, remains controversial. The purpose of this review is to analyze the incidence and risk factors for local recurrence after initial treatment of invasive breast cancer. Studies using multivariate analysis to account for other known prognostic factors have shown that age may not be an independent predictor of locoregional recurrence.[16, 24-26] Recht et al[26] demonstrated on multivariate analysis that the number of positive axillary nodes and total number of nodes examined—but not age—were significant independent factors for locoregional recurrence. According to a statistical model reported by Iyer et al[34], inaccuracy of the staging of a patient with ? 4 positive nodes vs 1 to 3 positive nodes increases as fewer total nodes are removed.
These factors may account for the 30% or higher rates of locoregional recurrence in the Danish and British Columbia series that would be more usual for patients with 4 or more positive nodes. In a series of node-positive postmenopausal women treated by mastectomy and tamoxifen (Nolvadex), Fisher et al[43] found that a positive margin was a significant predictor of locoregional recurrence on multivariate analysis. Mentzer et al[44] reported outcomes from a series of patients with stage II disease (two-thirds with positive nodes) who were treated by modified radical mastectomy, with or without systemic therapy.
In another series of 608 patients treated with mastectomy, with or without systemic therapy, and postmastectomy chest wall irradiation in 8%, Jager et al[27] found no statistical difference in locoregional recurrence between 57 patients with close (< 5 mm) or positive margins and 551 patients with negative margins. Tamoxifen alone or when added to chemotherapy also produces a modest reduction in the risk of chest wall recurrence.[26,33] Fisher et al[55] reported the 10-year results from a trial by the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14 in which node-negative patients with ER-positive tumors were randomized to tamoxifen or observation. Goldhirsch et al[56] reported a meta-analysis of five trials of adjuvant systemic therapy in node-positive patients treated by mastectomy without radiation. Nonlinear Models These procedures are used to fit smoothed curves and surfaces to two-dimensional or multidimensional data. The Spline Interpolation procedure fits smooth curves to X-Y data by linear, cubic, or tension spline interpolation. Polynomial Regression is used to fit a polynomial regression model of a dependent variable on one or more independent variables using polynomials up to degree nine. This study was approved by the Institutional Review Board (IRB) of the University of Michigan Hospitals (IRB study #2003-0128). A retrospective analysis of data from all patients admitted to the University of Michigan Hospitals from 1993 to 2009 who underwent aortic arch replacement via a median sternotomy was performed (n=721). Figure 2 Kaplan-Meier survival analysis stratified by presence of type A aortic dissection. While TEVAR was not an option for the majority of patients in this study, it is important to note that certain groups emerge as ideal candidates for application of this newer technology for the arch aorta. Annals of Cardiothoracic Surgery (Ann Cardiothorac Surg, Print ISSN 2225-319X; Online ISSN 2304-1021).
The standard management of an ipsilateral breast tumor recurrence following breast-conserving surgery and radiation is salvage mastectomy, while local excision and radiation are optimal treatment of a chest wall recurrence following initial mastectomy.
The management of each patient requires a multidisciplinary approach that depends not only on factors specific to the recurrence itself but also on factors related to the original treatment. There is a strong association between local recurrence and the appearance of simultaneous or subsequent distant metastases. Four of these trials report similar risks of local failure associated with these two methods of treatment for early-stage invasive breast cancer. In another radical mastectomy series, Donegan et al[21] observed a similar crude failure rate of 67% for ages 20 to 29 years and 46% for ages 20 to 39 years, compared with < 25% for those ? 40 years of age. Pisansky et al[16] also used multivariate analysis to show that tumor size, nodal status, and estrogen-receptor (ER) status, not age, were significant independent factors for locoregional recurrence. In a series of 57 patients with gross multicentric disease treated by mastectomy, Fowble et al [31] reported a low (< 10%) risk of chest wall recurrence in the absence of ? 4 positive nodes or T3 tumor size.
For example, the model predicts that in order to have a 90% probability of accurately ruling out 4 or more positive nodes, a patient with 1, 2, or 3 positive nodes and a T1 tumor size would need 8, 15, or 20 nodes examined, respectively. Benson and Thorogood[35] reported a prospective nonrandomized trial of total mastectomy with either an axillary dissection or axillary sampling. The largest reported series of patients with 1 to 3 positive nodes treated with mastectomy and adjuvant systemic chemotherapy has recently been updated by Recht et al.[26] Among 983 patients with T1-2 tumors and 1 to 3 positive nodes, the 10-year cumulative incidence of local failure was only 8%.
Two-thirds of these patients were assessed using gross margins, which is less accurate than microscopic assessment,[42] and one-quarter also received postmastectomy radiation, which minimizes the rate of chest wall failure with a close or positive margin.[46] The crude local recurrence rate was nearly four times higher in patients with a margin of 5 mm or less compared to patients with margins greater than 5 mm (11% vs 3%), but this finding was not statistically significant. In the aforementioned series of mastectomies for T1-2 tumors investigated by O’Rourke et al,[50] there was a 36% risk of chest wall recurrence with lymphovascular invasion, compared to a 19% risk without lymphovascular invasion. Approximately 2,108 patients received adjuvant systemic chemotherapy with (815) or without (1,293) tamoxifen or with oophorectomy (166), and 722 patients received no systemic therapy or only one cycle of chemotherapy. The Kaplan-Meier survival curve generated for the entire cohort is demonstrated in Figure 1. When separated by indication for intervention, the survival of the group presenting with acute type A aortic dissection has a poorer prognosis than those presenting with other pathology.
Early results indicate that the dreaded complications of arch repair, namely death and stroke, can occur at rates under 5%. These include older patients, those with renal failure, and those with acute type A dissection. Long-term results from a 12-year experience with endovascular therapy for thoracic aortic disease. Prospective comparative study of brain protection in total aortic arch replacement: deep hypothermic circulatory arrest with retrograde cerebral perfusion or selective antegrade cerebral perfusion.
Retrograde and antegrade cerebral perfusion: results in short elective arch reconstructive times. Selective antegrade cerebral perfusion via right axillary artery cannulation reduces morbidity and mortality after proximal aortic surgery.

Contemporary open aortic arch repair with selective cerebral perfusion in the era of endovascular aortic repair. The aortopathy of bicuspid aortic valve disease has distinctive patterns and usually involves the transverse aortic arch.
Methods: A retrospective review was performed of 258 consecutive patients with aortic stenosis (AS) who underwent AVR between August 2002 and December 2010 at Juntendo University Hospital.
In many cases, local recurrence may be a manifestation of a more aggressive tumor biology that heralds the presence of distant metastases. Multidisciplinary management of an isolated chest wall recurrence after mastectomy and an ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery and radiation will be discussed separately. The National Cancer Institute (NCI) and the European Organization for Research and Treatment of Cancer (EORTC) trials reported significantly higher rates of local failure for patients treated with breast-conserving surgery and radiation, compared to those treated with mastectomy. Viewed in another way, the odds that a patient with a T1 tumor and 1, 2, or 3 positive nodes but with only 7 nodes examined actually has 4 or more positive nodes are 13%, 55%, or 93%, respectively. The risk of a chest wall recurrence was 16%, 21%, or 27% for grade I, II, or III tumors, respectively. This difference remained significant on multivariate analysis, as did lymph node status and tumor grade. In those treated with mastectomy, there was no difference in the subsequent chest wall failure rate, with or without overexpression. At 20 years, there was no significant difference (15% vs 13%) in the rate of locoregional recurrence as a first event, with or without chemotherapy. As the Stanford group has suggested in their analysis of patients presenting with bicuspid aortic valve and ascending aneurysms, most patients will have enlargement in the root and proximal ascending aorta, where the complex anatomy of the sinuses, sinotubular junction and the coronary ostia make TEVAR unfeasible with current technology (11). Regardless of this association, durable local salvage is important in preventing the consequences of uncontrolled locoregional disease.
Inadequate surgery for the primary may have contributed to the higher rate of IBTR in these trials, since only gross removal of the tumor was required. The model suggests that these randomized trials found higher rates of locoregional recurrence in patients with 1 to 3 positive nodes because a significant number were understaged by the small median number of nodes removed.
Recht et al[26] found that a greater number of nodes examined—from 2 to 5, 6 to 10, or ? 11—was associated with a decreased risk of locoregional failure that was independent of the number of positive nodes on multivariate analysis.
These differences remained significant on multivariate analysis, as did lymph node status and lymphovascular invasion. In contrast, Zellars et al[52] found that p53-positive patients had a higher risk of local failure after mastectomy—with or without radiation—that remained significant on multivariate analysis. Although not identified as an independent risk factor on multivariate analysis, type A dissection did have an important time-dependent effect on mortality, particularly during the early postoperative period (Figure 2). Late results suggest important risk factors for death include age, impaired renal function and a prior history of CABG. Their work suggests that in identifying an endovascular solution to the ascending aorta, a valved conduit that addresses the coronary arteries may need to be considered as an option. Thus, operative mortality was higher in the older patients compared with the younger patients, but was not statistically significant between the two groups. A prolonged interval between initial treatment and local recurrence is the most important prognostic factor for subsequent outcome, and when combined with other favorable characteristics, can predict 5-year survival rates of 70% or higher. However, if distant metastases are a common but not universal outcome after clinically isolated local recurrence, there may be a subgroup of patients for whom successful local salvage could result in long-term disease-free and overall survival. Outcome and independent prognostic factors after salvage of a local recurrence will be reviewed, with particular attention given to the association between the clinically isolated local recurrence and subsequent distant metastases.
For example, in the breast-conserving surgery arm of the EORTC trial, 81% had T2 tumors, and 48% of all patients had microscopically positive margins. In another series of 404 mastectomy patients with T1-2 tumors and 1 to 3 positive nodes, Katz et al[36] reported a locoregional recurrence risk of 24% with less than 10 nodes removed vs 11% for 10 or more nodes removed (P = .02). Seminal work by Crawford and associates demonstrated that these techniques could result in death and stroke rates of 10% and 7% respectively (3).
Multivariate models were constructed to identify factors that were independently associated with each of the outcomes of interest. Given the emerging role of thoracic aortic endovascular repair (TEVAR) and its encroachment into the arch segment, we initiated an evaluation of open arch reconstruction to identify the important risk factors for poor outcomes, and define its late results (4). Patients aged 80 years and older were significantly more likely to suffer from respiratory failure after surgery than younger patients, but there were no significant differences in any other complications between the two age groups.
Three-year survival was 84% in patients aged more than 80 years, and 83% of these elderly patients were living at home at the last follow-up.
In this population, the most common structural cardiac disease is degenerative calcified aortic stenosis [1]. Current guidelines [2,3] demonstrated AVR as class I recommendation in symptomatic patients with AS, however, there remains significant reluctance to recommend AVR in patients greater than 80 years old [4] due mainly to the increased risk of operative mortality and morbidity in this age group.
A recent study indicated that about 40% of octogenarians with AS either refused or were not proposed for AVR, although the operation was indicated on the basis of current guidelines [4].In recent years, transcatheter aortic valve implantation (TAVI) has emerged as a less invasive alternative to AVR for patients with AS considered to be at very high surgical risk.
Therefore, there is increasing interest in evaluation of outcomes after AVR in elderly patients. The aim of this study was to report our clinical experience in a contemporary series of AVR for AS with or without CABG, compare the early and mid-term results between patients aged more than 80 years and those aged less than 80 years, and determine the risk factors for early morbidity and mortality, non-home discharge, and mid-term mortality.2. Patients and DataBetween August 2002 and December 2010, 258 consecutive patients underwent AVR for AS at Juntendo University Hospital, including 82 patients with concomitant CABG.
Patients were excluded from this cohort study if they required concomitant mitral or tricuspid valve surgery.
Outcome measures included operative mortality, postoperative complications (respiratory failure, renal failure, stroke, reoperation for any reason, deep sternal wound infection, gastrointestinal complication, systemic infection, pacemaker implantation for complete atrioventricular heart block), non-home discharge, and mid-term mortality.

Operative mortality was defined as death within 30 days of surgery or as death at any time before discharge from hospital. Respiratory failure was defined as prolonged postoperative ventilation (>24 hours) or need for reintubation or tracheostomy. Operative ProceduresAll surgical procedures were performed through a median sternotomy using cardiopulmonary bypass with systemic normothermia.
Myocardial protection was achieved using antegrade and retrograde administration of high-potassium cold blood cardioplegia. Statistical AnalysisCategorical variables are given as percentage and were compared between groups using chi-square test or Fischer’s exact test. Continuous variables are reported as mean ± standard deviation and were compared between groups using the unpaired t-test.
Variables that achieved a p value less than 0.1 in the univariate analysis were then examined using multivariate analysis by multiple logistic regression to evaluate independent risk factors for outcomes.
Independent predictors of mid-term survival were determined with the Cox proportional hazards multivariate analysis. RESULTSDemographic Data, Preoperative Risk Factors, and Operative Data.A total of 258 patients were studied.
Operative mortality was higher in the older patients compared with the younger patients, but was not statistically significant. Postoperative ComplicationsForty-six patients (17.8%) developed at least one postoperative complication (Table 3).
Among the major postoperative complications examined, the incidence of respiratory failure was significantly greater in the patients aged 80 years and older, but there were no significant differences in any other complications between the age groups (Table 3). Therefore, the higher incidence of postoperative complications in patients aged 80 years and older is explained by a greater incidence of respiratory failure in this group.
There was no statistical significance between the two age groups regarding mid-term survival.
DISCUSSIONWith increasing number of patients with AS, particularly in elderly patients with relevant concomitant disease, being referred for surgery, evaluation of surgical results in patients aged more than 80 years has become a major concern [1,4]. In recent years, TAVI has emerged as a less invasive alternative to AVR for elderly patients with AS at very high surgical risk, particularly in octogenarians, but controversy exists about whether high risk elderly patients actually benefit from TAVI compared with AVR [6]. Therefore, we have evaluated the early and mid-term outcomes after AVR between patients aged more than 80 years and those aged less than 80 years,Figure 1. Overall survival stratified by age: 80 years and older (solid line) and less than 80 years (dashed line). Overall survival stratified by NYHA class: NYHA class III-IV (solid line) and NYHA class II (dashed line). Operative MortalityThe results of the current study demonstrate that good results after AVR can be expected in patients aged 80 years and older with slightly increased risk of operative mortality and morbidity compared with younger patients.
Mid-term results in patients aged 80 years and older are also satisfactory with more than 80% of survival at 3 years.
Previous studies, in the mid-1990s and earlier, analyzing results of isolated AVR or AVR + CABG reported operative mortality between 9% and 28% in patients aged over 80 years [7-9].
However, studies in the last decade have demonstrated improvement in operative mortality between 5% and 10% [10-15] (Table 5). Our routine adjunctive perioperative practice includes CT scan for detection of vascular calcification, preoperative nasal culture of MRSA (methicillin-resistant staphylococcus aureus), both antegrade and retrograde administration of cardioplegia, and routine postoperative cardiac rehabilitation.
This might be due to the small number of patients in our study, but similar results have been reported in large studies analyzing outcome of AVR in octogenarians [11,14] (Table 5). Postoperative Complications and Non-Home DischargeThe current study showed a statistically significant increase of postoperative complications in the older patients compared with the younger patients. This is largely due to the significantly higher incidence of respiratory failure in patients aged more than 80 years. However, there was no difference in any other complication between the two age groups (Table 3).
The recent literature has shown similar morbidity results, and reported that elderly patients were significantly more likely to suffer from respiratory failure than younger patients [11,14].Non-home discharge as a measure of postoperative recovery is an important issue when evaluating outcome of AVR. At the last follow-up in the current study, 6 out of 9 patients aged more than 80 years discharged to non-home location returned home and are leading satisfactory lives, and thus a total of 83% (n = 34)Table 5.
Mid-Term SurvivalIn the current study, survival estimates for patients aged more than 80 years at 1, 3, and 5 years were 89%, 84%, and 84%, respectively (Figure 1).
This compares well with recent large studies reporting long-term survival of AVR in octogenarians (Table 5). LimitationsThe current study is limited by its retrospective nature and selection bias inherent in the data. Another limitation is that relatively small number of patients, which might be a reason of why potential risk factors such as old myocardial infarction, diabetes mellitus, and concomitant CABG, were not found to be of multivariate significance of outcomes.5. CONCLUSIONGood results after AVR can be expected in patients aged 80 years and older, with slightly higher operative mortality and morbidity compared with younger patients. Midterm survival in elderly patients is very acceptable, with more than 80% survival at 3-year after AVR. These satisfactory results of conventional AVR in patients aged 80 years and older, as well as independent risk factors for outcomes found in the current study have to be taken into consideration in the decision-making process regarding treatment strategy for patients with AS.

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