Oncoplastic Level 2 Mammoplasty for Large DCIS: 5-Year Results.

BACKGROUND: Oncoplastic surgery (OPS) allows wider resections with immediate breast reshaping by mammoplasty. This study reviews our experience with level 2 mammoplasties in patients with histology-proven pure ductal carcinoma in situ (DCIS). METHOD: From a prospectively maintained database of 392 consecutive oncoplastic level 2 mammoplasties, 68 patients presented with pure DCIS. Involved margin rates and locoregional recurrence rates were calculated, with 76 months (0-166 months) median follow-up. RESULTS: The mean pathological tumor size was 34 mm (median 26 mm, range 2-106 mm). The mean resection weight was 191 g (median 131 g, range 40-1150 g). Margins were clear in 58 cases (85.3%) and involved in 10 cases (14.7%). Margins were involved in 1 out of 54 (1.9%) cases with tumor size under 50 mm and in 9 out of 14 (64.3%) cases with tumor size higher than 50 mm (p < 0.001). On multivariable analysis, only tumor size > 50 mm [odds ratio (OR) 95.400; p < 0.001] was independently associated with involved margins. Seven patients had mastectomy. The overall breast conservation rate was 89.4%, and 100% for tumors less than 5 cm. There were three local recurrences. The 5-year cumulative incidence for local recurrence was 5.5% (0-11.5%). CONCLUSIONS: OPS is a safe solution for large DCIS up to 50 mm, with an involved margin rate of only 1.9%, and can thus reduce the mastectomy rate in this group. As margin involvement significantly increases for tumors larger than 5 cm, better preoperative localization and/or wider excisions are necessary in this group.

A prospective randomized study comparing centrifugation and sedimentation for fat grafting in breast reconstruction.

BACKGROUND: Fat grafting is an efficient method to correct large volumetric defects after mastectomy. There is an ongoing debate regarding the best method of processing the harvested fat before fat grafting. This study aimed to introduce a new MRI model and to compare two fat processing techniques measuring the gain in soft tissue thickness after fat grafting to the chest wall. METHODS: Fifty-one mastectomy patients (one double sided), who required delayed implant reconstruction, with poor skin conditions were proposed fat grafting prior to implant reconstruction. At the time of fat grafting, patients were randomly assigned to centrifugation or sedimentation of the aspirated fat. The trial was undertaken in a single-center private practice setting. The gain in soft tissue thickness of the chest wall was measured using an MRI model, with 12 predefined points for measurement. Two MRIs were performed, one prior to fat grafting and one 8 weeks thereafter. The radiologist was blinded to the fat graft processing method used. RESULTS: Seven cases were excluded because they did not complete their second MRI. The analyses were thus based on 44 patients (one double sided). Centrifugation was performed in 21 cases and sedimentation in 24 cases. The mean gain in soft tissue thickness was +7.0 mm in the centrifugation group and +8.8 mm in the sedimentation group (p = .268). The mean operative time was 88 min in the centrifugation group and 78 min in the sedimentation group (p = .11). There were no adverse events for any of the patients. CONCLUSIONS: We developed a simple and reproducible MRI model to objectively measure and evaluate different fat processing techniques prior to fat grafting. At a median time of 8 weeks after one session of fat grafting, there was no benefit of centrifugation over sedimentation.

Occult cancer in specimens of reduction mammaplasty aimed at symmetrization. A multicentric study of 2718 patients.

Women who have undergone surgical treatment for breast cancer often benefit from a contralateral reduction mammaplasty (CRM) aimed at symmetrization of the contralateral breast unaffected by the initial cancer. In our 7-year multicentric study (12 centers) of 2718 patients, incidence of CRM cancers (CRMc) was 1.47% (n = 40) [95% CI 1.05%-2.00%]. The CRMc group had significantly more initial mammary cancers of invasive lobular carcinoma (ILC, 22.5% vs 12.0%) and ductal carcinoma in situ (DCIS, 35.0% vs 21.6%) types than the healthy CRM group (p = 0.017). 35.0% (n = 14) of patients had en bloc resection; 25.0% (n = 10) of surgical specimens were correctly oriented. En bloc resection and orientation of surgical specimens enable precise pinpointing of the CRMc. A salvage lumpectomy may be proposed as an option when margins are invaded. The histological distribution of the 40 CRMc (mean size 12.7 mm) was carcinoma in situ (CIS) 70%, ILC 12.5%, invasive ductal carcinoma (IDC) 12.5% and tubular carcinoma (TC) 5.0%.

A new level 1 oncoplastic technique for breast conserving surgery: rotation glandular flap.

BACKGROUND: When performing conservative surgery for breast cancer, breast reshaping can be a challenging procedure. Level 1 oncoplastic surgery (OPS) techniques, i.e., advancement or rotation of glandular flaps, should be performed when less than 20 per cent breast volume is excised. OBJECTIVE: A new Level 1 OPS technique is described. A wide centro-lateral glandular flap is created after extensive undermining of the skin and nipple-areolar complex, and rotated into the cavity. DISCUSSION: This rotation glandular flap is a new technique for use following a wide excision, in glandular, not fatty, breasts, and when standard closure of the cavity would not leave a satisfactory cosmetic result.

[Autologous fat grafting to the postmastectomy irradiated chest wall prior to breast implant reconstruction: a series of 68 patients]. / Transfert de tissu adipeux autologue préalable à la reconstruction mammaire par implant après mastectomie et irradiation : à propos d'une série de 68 cas.

INTRODUCTION: After radiotherapy, breast reconstruction with an implant carries a high risk of failure and complication. Clinical and experimental studies have demonstrated that grafting adipose tissue (lipofilling) in an irradiated area enhances skin trophicity. Thus, we have started performing preliminary fat grafting to the irradiated chest wall prior to implant reconstruction in order to limit complications and failure risk. PATIENTS AND METHODS: Patients were included in this study from 2007 to 2011. All patients had had mastectomy and irradiation for breast cancer. They all had one or more sessions of lipofilling prior to breast implant reconstruction. These patients were prospectively followed up in order to collect the following data: postoperative complications; cosmetic result; local breast cancer recurrences. RESULTS: Sixty-eight patients were included. The mean number of fat grafting sessions was 2.3 (range 1-6). An average volume of 115mL (70-275) was injected each time. The mean volume of breast implants was 300mL (185-400). The mean follow-up was 23months (450). No breast cancer local recurrence was diagnosed during follow-up. Implant explantation was performed in one case (1.47%) The mean cosmetic result was 4.5/5. CONCLUSION: Fat grafting to the irradiated chest wall prior to implant placement might be an alternative to flap reconstruction for patients who are not suitable or who refuse this option.

Adipose-tissue grafting to the post-mastectomy irradiated chest wall: preparing the ground for implant reconstruction.

INTRODUCTION: Breast implant reconstruction after radiotherapy carries a high risk of failure and complication. Nevertheless, it may be the only alternative for patients who are not suitable for autologous reconstruction or who refuse this option. As clinical and experimental studies have demonstrated that grafting adipose tissue (lipofilling) in an irradiated area improves the quality of the skin, we made the assumption that preliminary fat grafting of the chest wall might reduce the complication and failure rates of implant reconstruction by improving the implant coverage. PATIENTS AND METHODS: From 2007 to 2009, 28 patients had fat transfer to the chest wall, prior to implant reconstruction. All patients had had mastectomy and irradiation for breast cancer. Lipofilling was initiated 6 months after the end of radiotherapy. The mean number of fat-grafting sessions was 2 (range 1-3). An average volume of 115 cc (70-275 cc) was injected each time. Once the chest wall's skin seemed to have gained enough thickness, implant reconstruction was performed. RESULTS: The mean follow-up period was 17 months. Three minor complications occurred. Implant explantation was performed in one case for exposition. The cosmetic results were good and very good in >80% of the cases. CONCLUSION: This study points out the benefits of fat grafting to the irradiated chest wall prior to implant placement and demonstrates that lipofilling prepares the ground to implant breast reconstruction. This approach could be considered as an alternative to flap reconstruction for selected patients.

[Partial reconstruction after conservative treatment for breast cancer: classification of sequelae and treatment options]. / Séquelles esthétiques du traitement conservateur des cancers du sein: une classification pour les reconstructions après tumorectomie.

Most patients presenting with breast cancer are treated by breast conserving treatment (BCT). Some of these patients present with poor cosmetic results and ask for partial breast reconstruction. These reconstructions following BCT are presenting more frequently to plastic surgeons as a difficult management problem. We have defined and published a classification of the different cosmetic sequelae (CS) after BCT into three types. This classification helps to analyse these complex deformities aggravated by radiotherapy. Furthermore, our classification helps to choose between the different surgical techniques and propose the optimal option for their surgical correction. Our initial publications reported 35 and 85 patients: we have currently operated more than 150 cases of CS after BCT. Type-1 CS are defined by an asymmetry between the two breasts, with no distortion or deformity of the radiated breast. Type-2 CS are those with an obvious breast deformity, that can be corrected with a partial reconstruction of the breast. Type-3 CS are those with such a deformity that only a mastectomy with total reconstruction of the breast can be performed. Most of the patients present with type-2 CS, but are reluctant to undergo what they feel is a major reconstructive procedure: in a initial prospective series of 85 patients operated for CS after BCT, 48 (56.5%) had type-1 CS, 33 patients (38.8%) type-2 CS and four patients (4.7%) type-3 CS. Type-1 patients should be managed essentially by contralateral symmetrizing procedures. One should limit any surgery on the radiated breast, as a mammoplasty or an augmentation is at high risk of complications. Type-2 is the most difficult to manage and requires all the surgical armamentarium of breast reconstructive surgery. The insetting of a myocutaneous flap is often necessary and autologous fat grafting is a promising tool in selected cases. Type-3 CS requires mastectomy and immediate reconstruction with a myocutaneous flap. The major development though in the past 10 years has been the development of oncoplastic techniques at the time of the original tumour removal, in order to avoid most of type 2 and type 3 deformities. This paper reaffirms the validity of the Cosmetic Sequelae classification as a simple, practical guide for breast reconstructive surgeons. It discusses the various choices of reconstructive procedures available, the importance of "preventing" these CS and defining the role of the plastic surgeon in the management of these patients.

[Breast reconstruction: late cosmetic results of implant reconstruction]. / Reconstruction mammaire par prothèse: vieillissement et résultats esthétiques tardifs.

The long cosmetic outcome of breast implant reconstruction is unknown. The morbidity and cosmetic outcome of 360 patients who underwent immediate breast reconstruction with various types of implant has been prospectively analysed over a 10-year period. 334 patients who completed their reconstruction were suitable for evaluation of their cosmetic outcome. The early complication rate (<2 months) was 9.1%, with an explantation rate of 1.6%. The late complication rate (>2 months) was 23%, with a pathological capsular contracture rate of 11% at two years and 15% at five years, and an implant removal rate of 7%. The revisional surgery rate was 30.2%. The cosmetic results were prospectively assessed using an objective five point global scale. Every patient was scored at each visit once surgery was completed. The overall cosmetic outcome deteriorates in a linear fashion from an initial acceptable result in 86% of patients two years after completion of their reconstruction to only 54% at five years. This fall off in the cosmetic outcome was not associated with the type of implant used, the volume of the implant, the age of the patient or the type of mastectomy incision employed. Radiotherapy was not a significant factor as only 28 patients were irradiated. However, on Cox model analysis pathological capsular contracture was the only factor which significantly contributed to a poor cosmetic outcome(P<0.0001 (relative risk 6.3). In spite of a high revisional surgery rate, deterioration still occurred, suggesting that other unaccounted for variables were responsible. On photographic retrospective review of those patients without a capsular contracture who demonstrated a deterioration in their cosmetic scores, it became clear that a possible reason for their poor result was late asymmetry produced by the failure of both breasts to undergo symmetrical ptosis as the patients aged.

Nicotine-stimulated elastase activity release by neutrophils in patients with abdominal aortic aneurysms.

Elevated elastase activity in patients with chronic obstructive pulmonary disease (COPD) is attributable to the direct effect of nicotine. COPD is also known to be an independent predictor of abdominal aortic aneurysm (AAA) growth and rupture. The purpose of this study is to determine the effect of nicotine on elastase activity release from neutrophils of AAA patients. Human neutrophils were extracted from the blood of subjects in the following six groups, n = 10 in each group: smoking AAA (SAAA), nonsmoking AAA (NSAAA), smoking aortic occlusive disease (SAOD), nonsmoking aortic occlusive disease (NSAOD), smoking controls (SC), and nonsmoking controls (NSC). After incubation with varying nicotine concentrations (0-1000 microg/ml), the released elastase activity was determined. There is generally an elevation in elastase activity release by neutrophils of smokers compared to nonsmokers. Nicotine exposure stimulated increased elastase activity release in AOD and AAA, and the increase was especially pronounced in the SAAA and SAOD groups. The elevation was greatest in the SAAA group while the release was lowest in the NSAOD group. There is a direct correlation between elastase activity release and nicotine concentration. The data suggest that COPD and AAA development, which may occur by similar initial mechanisms may also be aggravated by nicotine-induced neutrophil elastase activity release. In addition, the results indicate that nicotine is playing an active role in the development of vascular disease by inducing neutrophils to release elastase activity.

Inhibition by protease inhibitors of chemotaxis induced by elastin-derived peptides.

We studied the effect of two inhibitors of human neutrophil proteases on neutrophil chemotaxis induced by the hexapeptide Val-Gly-Val-Ala-Pro-Gly (VGVAPG), a recurring sequence in the elastin molecule. The inhibitors were tosyl-Phe chloromethyl ketone (TFCK) and N-methoxysuccinyl-Ala-Ala-Pro-Val chloromethyl ketone (MAAPVCK). We assayed chemotactic activity by the double-membrane technique in a modified Boyden chamber, after incubating the cells for 1 hr with varying concentrations of inhibitor. We observed a concentration-dependent inhibitory effect. We also measured the potency of the two chloromethyl ketones as protease inhibitors. The more potent protease inhibitor, MAAPVCK, was also the more effective in inhibiting VGVAPG-induced chemotaxis; its inhibitor dissociation constant was KI = 28 nM with elastase and KI = 33 nM with cathepsin G. For TFCK the corresponding KI values were 37 microM and 200 microM. The incubating concentration required to lower chemotaxis by half its uninhibited value was C0.5 = 0.64 microM for MAAPVCK, compared to C0.5 = 3.4 microM for TFCK. A third peptide, triglycinate (gly3), which did not inhibit the proteolytic activity of either elastase or cathepsin G, did not inhibit chemotaxis. Chemotaxis induced by formyl Met-Leu-Phe (fMLP) was weakly inhibited by both chloromethyl ketones with TFCK being somewhat more effective than MAAPVCK. We concluded that inhibition of VGVAPG-induced chemotaxis is in part specific, receptor mediated. We suggest that proteolytic inhibitors protect the extracellular matrix from degradation by inhibiting chemotaxis. Comparing the inhibitor concentrations required to half proteolytic activity with the concentration required to half chemotactic activity, we further suggest that the two functions may be of comparable significance.

Role of the neutrophil in abdominal aortic aneurysm development.

Elastase release by neutrophils has been implicated in the etiology of abdominal aortic aneurysm (AAA). The present study investigated whether neutrophils in patients with AAA actively synthesize the neutrophil elastase enzyme and the effect of elastin-derived peptides on neutrophil elastase release. Total neutrophil elastase in patients with AAA was significantly higher than in those with aortic occlusive disease and controls. The neutrophil elastase gene was not expressed in any patient group. Elastin-derived peptides induced elastase release, which was significantly higher in patients with AAA than in those with aortic occlusive disease and controls. These data indicate that the peptides of elastin degradation stimulate the release of elastase, but that continuing production of elastase is absent in circulating neutrophils. It is concluded that: (1) neutrophils do not actively synthesize elastase but act as 'mules' or carriers of the enzyme; and (2) elastin breakdown products stimulate the release of elastase at the aortic wall by circulating neutrophils, which in patients with AAA have a predetermined increased amount of elastase.

Increased intestinal permeability: implications for thoracoabdominal aneurysm repair.

Coagulopathy and massive bleeding plays a major role in the mortality of thoraco-abdominal aneurysm repair. Increasing supraceliac aortic cross-clamp time from 0 to 90 minutes increases the degree of disseminated intravascular coagulation, which occurs as a result of occlusion and reperfusion of the superior mesenteric artery. The purpose of this study was to investigate the mechanism of the superior mesenteric artery reperfusion disseminated intravascular coagulation. Twenty dogs were divided into four groups: cross-clamp time of 30 minutes; cross-clamp time of 60 minutes; cross-clamp time of 90 minutes; and control. Permeability was determined by lactulose/mannitol absorption. The venous effluent was sampled for endotoxin, potassium, bacteria, and pH every hour and urine was collected for six hours. Lactulose absorption was significantly higher in all of the experimental groups. There was increased permeability in the 60 and 90 minute groups which correlated significantly with time. Venous endotoxin, potassium, and blood cultures for bacteria did not change significantly. The pH was significantly lower every hour for six hours in the 90 minute group. These data suggest that intestinal permeability is increased with supraceliac aortic clamping and can be kept to a minimum for clamp times of under one hour.

Smooth muscle cell elastase, atherosclerosis, and abdominal aortic aneurysms.

Smooth muscle cells (SMC) were obtained by outgrowth of human aortic explants from abdominal aortic aneurysm (AAA) patients, aortic occlusive disease (AOD) patients, and transplant donors (controls). Specimens were incubated with medium alone or medium with either elastin-derived peptides (EDP, 5 micrograms/mL) or low-density lipoproteins (LDL, 5 micrograms/mL). Elastase activity (ng/mg total protein) was assayed from 4-week-old cultures. Control aortas obtained from patients significantly younger secrete an increased amount of elastase at baseline compared with AOD and AAA patients (p less than 0.05). Elastin-derived peptides caused a significant increase in elastase secretion in all groups. The increase in elastase secretion in response to EDP in AAA patients was significantly higher compared with AOD or control. Low-density lipoprotein had no effect on SMC elastase secretion. These data suggest that (1) aortic SMCs secrete elastase in response to EDP, (2) SMC elastase is age dependent, and (3) AAA SMC secrete an abnormally high amount of elastase compared with AOD and control aortas in response to EDP. Like the neutrophil, the SMC is highly responsive to the degradation products of elastin and in AAA patients secrete significantly increased amounts of elastase in response to the breakdown products of atherosclerosis.

In vivo inactivation of antithrombin III is promoted by heparin during cardiopulmonary bypass.

To study the in vivo effect of heparin on antithrombin III (AT3) when elastase is elevated, the blood of 20 patients undergoing cardiopulmonary bypass (CPB) was assayed for elastase and AT3. The model was chosen because CPB is known to increase plasma elastase and the patients were heparinized. The blood of 20 patients undergoing cardiac surgery was assayed for elastase and AT3 one day preoperatively, every half hour during CPB, and one day postoperatively. Elastase increased significantly and AT3 decreased significantly during CPB. There was a direct correlation between the rise in elastase and decrease in AT3. AT3 decreased even further when elastase was elevated and patients were heparinized (AT3/elastase = 0.04 + 0.07), compared with the drop with elevated elastase alone (AT3/elastase = 0.11 + 0.14) (P less than .0015). These data indicate that (1) CPB is associated with an increase in plasma elastase, (2) elevated plasma elastase is associated with a reduction in AT3, and (3) heparin promotes the inactivation of AT3 when serum elastase is increased. These data confirm the in vitro observation that heparin accelerates the inactivation of AT3 in the presence of elastase.

Neutrophil chemotaxis and neutrophil elastase in the aortic wall in patients with abdominal aortic aneurysms.

To test the hypothesis that elastin-derived peptides (EDP) from human aortic tissue may be chemotactic for inflammatory cells, we studied the chemotaxis of neutrophils and monocytes to EDP derived from abdominal aortic aneurysm (AAA), aortic occlusive disease (AOD), and control aortas. In addition, we determined if neutrophils deliver neutrophil elastase to the aorta in vivo by staining for neutrophil elastase (NE) throughout the course of abdominal aortic aneurysms with the monoclonal antibody to human NE. EDP from AAA, AOD, and control tissue demonstrated significant chemotactic activity for both neutrophils and monocytes. All neutrophils had a greater attraction to EDP from AAA tissue compared to AOD and control aorta. Neutrophils from AAA patients were more attracted to EDP of AAA tissue than were neutrophils of AOD or control patients attracted to their respective aortic EDP. Neutrophil elastase stained positive in the adventitia and thrombus throughout the course of the aneurysm, but was not found in the intima, media, or plaque of the aorta.

The inactivation of antithrombin III by serum elastase in patients with surgical infections.

The relationship between serum elastase and antithrombin III was determined in septic surgical patients as a possible mechanism for intravascular thrombosis and hypercoagulability during sepsis. Eighteen patients with surgical infections and elevated white blood cell counts had their blood assayed daily for white blood cell count, serum elastase, and antithrombin III, until the patient's white blood cell count returned to normal. Antithrombin III was significantly lower (0.87%) when elastase was above the normal range (greater than 14.2 micrograms/ml). Elastase was significantly higher (30.6 micrograms/ml), when antithrombin III was less than normal. These data indicate that elevated serum elastase is associated with a significant reduction in circulating antithrombin III. Stimuli that increase serum elastase, i.e. surgery, trauma, or sepsis may promote intravascular thrombosis by the inhibition of antithrombin III at the blood-endothelial cell interface.