Sub-muscular Reconstruction after NAC Sparing Mastectomy: Direct to Implant Breast Reconstruction with Human ADM Versus Tissue Expander.

BACKGROUND: Nipple areola complex (NAC) sparing mastectomy allows good oncological and aesthetic results. The study compares the results, in terms of self-evaluated satisfaction and symmetry, of direct to implant (DTI) sub-muscular breast reconstruction, with the aid of human acellular dermal matrix (ADM) versus two-stage reconstruction with sub-muscular tissue expander, followed by implant. MATERIALS AND METHODS: This is a retrospective, observational, single-center, non-randomized, case-control study. Inclusion criteria were: unilateral NAC sparing mastectomy at Forlì Hospital between 2014 and 2018; sub-muscular reconstruction; minimum follow-up of 12 months from the reconstructive stage; no history of radiotherapy. Patients were divided into two groups: group A included patients who underwent DTI breast reconstruction with the aid of human ADM; group B were those who underwent a two-stage reconstruction with tissue expander then implant. We collected data on: (1) Self-evaluated satisfaction by Breast Q questionnaire (scores from 0 to 100). (2) Observer-evaluated symmetry. Bi-dimensional photographs were collected and evaluated by 11 breast surgeons blinded to each other, who assigned a score for symmetry (from 0 to 10). (3) Symmetry of anthropometric measures collected by hand and volume estimated by Breast V application. RESULTS: Group A included 28 patients; group included B 26 patients. Breast-Q questionnaires reported the following results: satisfaction with breasts in group A 65 ± 12 versus group B 68 ± 14; satisfaction with outcome in group A 88 ± 16 versus group B 93 ± 11; psychosocial well-being in group A 71 ± 20 versus group B 76 ± 17; sexual well-being in group A 63 ± 26 versus group B 60 ± 13; physical well-being in group A 68 ± 15 versus group B 60 ± 12. The average symmetry breast score assigned to group A was 6.9, versus group B 7.2. Regarding the anthropometric measures in group A, the differences between right and left were major to those in group B. Regarding breast volume, the mean difference between right and left in group A was 31.89 cc ± 24.97, whereas in group B was 25.46 cc ± 23.59. CONCLUSION: Our data show better symmetry and better psychosocial well-being in the two-stage reconstruction, and higher satisfaction with sexual and physical well-being in DTI reconstructions. These aspects should be discussed with the patient while collecting the informed consent. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bipedicled Nipple-Sparing Mastectomy Versus Traditional Nipple-Sparing Mastectomy: Comparison of 2 Alternative Techniques in Order to Save Nipple-Areola Complex.

BACKGROUND: Nipple-areola complex-sparing mastectomy (NSM) represents, when a mastectomy is unavoidable, the best treatment possible that can be offered to attenuate the negative impact of surgery on patients' quality of life. Unfortunately, NSM can be used only in selected patients with small and nonptotic breasts. In order to save the nipple-areola complex (NAC) also in patients with large and ptotic breast, otherwise subjected to a skin-sparing mastectomy with the sacrifice of the NAC, we described the bipedicled nipple-sparing mastectomy (BNSM). The aim of this study is to obtain a formal outcome assessment of BNSM and analyze the complications rate of this technique compared with traditional NSM. We furthermore attempt to describe the surgical procedures present in the literature that allow to preserve NAC also in large and ptotic breasts presenting the complication rates observed and comparing with our technique. Aesthetic outcome has also been evaluated. METHODS: We retrospectively reviewed 42 procedures of consecutive patients undergoing immediate reconstruction with tissue expanders after NSM (20 patients) or BNSM (19 patients). We divided them in 2 groups focused on surgical complications and aesthetic outcome. RESULTS: On a total of 42 procedures, the principal major complication was dehiscence of surgical wound procedures needing 1-day surgery revision occurring in 3 (14.3%) of the BNSM group and 1 (4.8%) of the NSM group, whereas as principal minor complication 4 partial NAC necrosis not requiring surgery in BNSM (19%) and 2 (9.5%) in NSM. No tissue expanders required explantation. Concerning cosmetic results, the overall appearance of the breast and NAC was acceptable in 85.7 % and 77.2%, respectively, in the NSM group and 80.7% and 66.7%, respectively, in the BNSM group. CONCLUSIONS: Bipedicled nipple-sparing mastectomy is a valid technique to improve patients' quality of life in large and ptotic breasts otherwise candidate to a skin-sparing mastectomy, but only a progressive learning curve can minimize complications. No significant statistical differences have been observed in terms of complication rates and aesthetical outcomes between the 2 groups. An accurate selection of patients is mandatory in order to obtain low complication rates and good aesthetical outcome.

A New Human-Derived Acellular Dermal Matrix for Breast Reconstruction Available for the European Market: Preliminary Results.

INTRODUCTION: The introduction of acellular dermal matrices (ADMs) contributed to the growing diffusion of direct-to-implant breast reconstruction (DTI-BR) following mastectomy for breast cancer. According to specific legislations, European specialists could not benefit from the use of human-derived ADMs, even though most evidence in the literature are available for this kind of device, showed optimal outcomes in breast reconstruction. The Skin Bank of the Bufalini Hospital (Cesena, Italy) obtained in 2009 the approval for the production and distribution of a new human cadaver-donor-derived ADM (named with the Italian acronym, MODA, for matrice omologa dermica acellulata) from the Italian National Transplant Center and National Health Institute. We report preliminary results of MODA application in direct-to-implant breast reconstruction following nipple-areola complex (NAC)-sparing mastectomy for breast cancer treatment. MATERIALS AND METHODS: We prospectively enrolled all women undergoing NAC-sparing mastectomy for breast cancer and DTI-BR in our breast surgical unit from June 2015 to January 2017. We enrolled a selected population without previous chest wall irradiation, not being heavy tobacco smokers or diabetic, with a BMI < 30 kg/m2 and requiring less than 550 cc silicone implants. We assessed short-term outcomes, defined as postoperative complications presenting in the first 30 postoperative days and long-term outcomes at 6 and 12 months. RESULTS: From June 2015 to January 2017, we treated 56 breasts. At a mean follow-up of 14 months, we observed only two minor complications described as limited wound dehiscences, conservatively managed with complete resolution without implant exposure or re-intervention. CONCLUSIONS: Our preliminary results show very good performance of MODA in direct-to-implant breast reconstruction following NAC-sparing mastectomy for breast cancer treatment. This is particularly relevant for the European market, where no other human-derived devices are available for breast reconstruction due to regulatory restrictions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A rare case of primary necrotising fasciitis of the breast: combined use of hyperbaric oxygen and negative pressure wound therapy to conserve the breast. Review of literature.

Necrotising fasciitis is a rare but potentially fatal disease. It is even more unusual as a primary disease of the breast. Surgical treatment is required in order to gain control over the spreading infection and mastectomy is reported to be the most common procedure. We report the first case of an otherwise healthy woman exhibiting a primary necrotising fasciitis of the breast, which was treated combining conservative surgery with hyperbaric oxygen (HO) and negative pressure wound therapy (NPWT). A 39-year-old woman presented to the emergency room with fever and swelling of her right breast. The physical examination showed oedema and erythema of the breast, with bluish blisters on the lower quadrant. Ultrasound and CT scans showed diffuse oedema of the entire right breast, with subdermal gas bubbles extending to the fascial planes. Few hours later the necrotic area extended regardless an IV antibiotic therapy; a selective debridement of all breast necrotic tissue was performed and repeated 7 days later. The HO was started immediately after the first surgery and repeated daily (2·8 Bar, 120 min) for 18 days and then a NPWT (120-135 mmHg) was applied. Forty-five days after the last debridement, the breast wound was covered with a full-thickness skin graft. Several months later, an excellent cosmetic result was observed. This is the first case of primary necrotising fasciitis of the breast treated associating HO and NPWT to surgical debridement only; this combination resulted in a complete recovery with the additional benefit of breast conservation. Such result is discussed in light of the available literature on the treatment of primary necrotising fasciitis of the breast.

Formal analysis of the surgical pathway and development of a new software tool to assist surgeons in the decision making in primary breast surgery.

BACKGROUND: The increased complexity of the decisional process in breast cancer surgery is well documented. With this study we aimed to create a software tool able to assist patients and surgeons in taking proper decisions. METHODOLOGY: We hypothesized that the endpoints of breast cancer surgery could be addressed combining a set of decisional drivers. We created a decision support system software tool (DSS) and an interactive decision tree. A formal analysis estimated the information gain derived from each feature in the process. We tested the DSS on 52 patients and we analyzed the concordance of decisions obtained by different users and between the DSS suggestions and the actual surgery. We also tested the ability of the system to prevent post breast conservation deformities. RESULTS: The information gain revealed that patients preferences are the root of our decision tree. An observed concordance respectively of 0.98 and 0.88 was reported when the DSS was used twice by an expert operator or by a newly trained operator vs. an expert one. The observed concordance between the DSS suggestion and the actual decision was 0.69. A significantly higher incidence of post breast conservation defects was reported among patients who did not follow the DSS decision (Type III of Fitoussi, N = 4; 33.3%, p = 0.004). CONCLUSION: The DSS decisions can be reproduced by operators with different experience. The concordance between suggestions and actual decision is quite low, however the DSS is able to prevent post- breast conservation deformities.

Repeat sentinel lymph node biopsy in patients with ipsilateral recurrent breast cancer after breast-conserving therapy and negative sentinel lymph node biopsy: a prospective study.

BACKGROUND: Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery with negative sentinel lymph node biopsy need a new axillary staging procedure. However, the best surgical option, i.e. repeat sentinel lymph node biopsy or axillary lymph node dissection, is still debated. Purpose of the study is to assess the performance of repeat sentinel lymph node biopsy. METHODS: In a multicenter study, lymph node biopsy completed by back-up axillary lymph node dissection was undertaken for ipsilateral breast tumor recurrence or new ipsilateral primary tumor. Tracer uptake was used to identify and isolate the sentinel lymph node during surgery, and it was classified after staining with hematoxylin and eosin and monoclonal anti-cytokeratin antibodies. Aside from negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. A multicenter, prospective study was conducted performing 30 repeat sentinel lymph node biopsy completed by back-up axillary lymph node dissection for ipsilateral breast tumor recurrence or new ipsilateral primary tumor in patients formerly treated with previous breast conservative surgery and negative sentinel lymph node biopsy. Negative predictive value, overall accuracy and false-negative rate of repeat sentinel lymph node biopsy were assessed. RESULTS: Sentinel lymph nodes were mapped in 27 patients out of 30 (90%). Aberrant drainage pathways were observed in one patient (3.7%). Tracer uptake was sufficient to identify and isolate the sentinel lymph node during surgery in 23 cases (76.6%); the patients in whom lymphoscintigraphy failed or no sentinel lymph nodes could be isolated underwent axillary lymph node dissection. The negative predictive value was 95.2%, the accuracy was 95.6% and the false-negative rate was 33%. CONCLUSIONS: Repeat sentinel lymph node biopsy is feasible and accurate, with a high negative predictive value. Patients with ipsilateral breast tumor recurrence or new ipsilateral primary tumor after previous breast conservative surgery and negative sentinel lymph node biopsy can be treated with repeat sentinel lymph node biopsy for the axillary staging and can be spared axillary dissection in case of absence of metastases. However, repeat sentinel lymph node biopsy may prove technically impracticable in about one quarter of cases and thus axillary lymph node dissection remains the only viable option in such instance.

Nipple areola complex sparing mastectomy.

Breast conservative therapy (BCT) is established as a safe option for most women with early breast cancer (BC). The best conservative mastectomy that can be performed, when mastectomy is unavoidable, is nipple-areola-complex sparing mastectomy (NSM), which allows the complete glandular dissection preserving the skin envelope and the nipple areola complex. In the treatment of BC, the cosmetic outcomes have become fundamental goals, as well as oncologic control. NSM is nowadays considered an alternative technique to improve the overall quality of life for women allowing excellent cosmetic results because it provides a natural appearing breast. The breast surgeon must pay attention to details and skin incision must be planned to minimize vascular impairment to the skin and the nipple. Preservation of the blood supply to the nipple is one of the most important concern during NSM because nipple or areolar necrosis is a well-described complication of this surgery. Another issue associated with the nipple preservation and the surgical technique is oncological safety related to nipple-areola-complex (NAC) involvement in patients with invasive BC. The authors present their experience on 252 NSM performed in the Breast Surgery Unit in Forlì. Careful selection of patients for this surgical procedure is imperative and many patients are not ideal candidates for this procedure because of concerns about nipple-areolar viability as women with significant large/ptotic breast, pre-existing breast scars and history of active cigarette smoking. To extend the benefits of nipple preservation to patients who are perceived to be at higher risk for nipple necrosis the authors describe technical modifications of NSM to allow nipple preservation and obtain good cosmetic outcomes.

Role of androgen and estrogen receptors as prognostic and potential predictive markers of ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a heterogeneous disease that has not been investigated as widely as invasive breast cancer. Thus, the search for biomarkers capable of identifying DCIS lesions that may recur or progress to invasive cancer is ongoing. Although conventional steroid hormone receptors, cell proliferation and other important tumor markers have been extensively studied in invasive tumors, little is known about the role played by androgen receptors (ARs), widely expressed in breast cancer, in DCIS. METHODS: We performed a retrospective study in a series of 43 DCIS patients treated with quadrantectomy only and followed up for a period ranging from 5 to 13 years, to evaluate the prognostic relevance of conventional biomarkers (estrogen receptor [ER], progesterone receptor [PgR], Ki67, human epidermal growth factor receptor 2 [HER2]) and AR. RESULTS: Our findings showed that AR and ER were not independent prognostic variables and that an AR/ER ratio cutoff of 1.13 showed a sensitivity of 75% and a specificity of 94% in predicting in situ relapse or progression to the invasive phenotype. Moreover, while the variables considered singly showed area under the curve (AUC) values ranging from 0.52% to 0.77%, the AR/ER ratio reached a very high AUC (0.92%). CONCLUSIONS: These preliminary results highlight the potentially important role of AR and ER and, in particular, of their ratio, as prognostic indicators of DCIS evolution.

Intra-operative radiological margins assessment in conservative treatment for non-palpable DCIS: correlation to pathological examination and re-excision rate.

What constitutes an adequate surgical margin in partial mastectomy is still controversial: intra-operative specimen radiogram is commonly used during partial mastectomy for nonpalpable lesions in order verify the adequacy of the resection but what margin is to be considered "adequate" is still debatable. An intraoperative specimen mammogram was performed during all consecutive conservative resections for nonpalpable DCIS and a 15-mm radiological margin was considered "adequate". Margins were pathologically assessed and classified as "negative", "close" or "positive" and the rate of margin involvement constitued the main outcome of the study. Among 272 conservative interventions, 80.51% had negative margins at final pathology, 3.31% had close margins and 16.18% had positive margins. An intraoperative "adequate" margin of 15 mm as defined on intraoperative specimen mammogram granted a high rate of histologically negative margin at primary surgery; this finding was paralleled by confirmation of the treatment as conservative in 95% of cases.

Biofunctional characteristics of in situ and invasive breast carcinoma.

PURPOSE: The increasing use of breast-conserving surgery makes it essential to identify biofunctional profiles responsible for the progression of in situ to invasive carcinomas to facilitate the detection of lesions that are most likely to relapse or progress and, thus, to be able to offer patients tailored treatment options. Our objective was to analyse and compare biofunctional profiles in ductal carcinomas in situ (DCIS) and invasive ductal carcinomas (IDC). We also aimed to identify markers in tumor and normal surrounding tissues that may be predictive of locoregional recurrence in patients with DCIS. METHODS: Biofunctional parameters including mitotic activity, estrogen receptor, progesterone receptor, microvessel density (MVD), c-kit and p27 expression were evaluated in 829 in situ and invasive carcinomas. The impact of the biomarker profiles of DCIS, IDC and normal surrounding tissues on loco-regional recurrence was analyzed. RESULTS: A progressive increase in cell proliferation and a concomitant decrease in steroid hormone receptor-positive lesions was observed during the transition from in situ to invasive carcinomas, as also within each subgroup as grade increased. Conversely, p27 expression and MVD dramatically decreased during the transition from in situ to invasive carcinomas. Finally, we found that a low c-kit expression was indicative of IDC relapse. CONCLUSIONS: Cell proliferation, hormonal and differentiation characteristics differed in DCIS with respect to IDC, and the main variation in the transition between the two histologic lesions was the decrease in p27 expression and MVD.

Improved sub-areolar breast tissue removal in nipple-sparing mastectomy using hydrodissection.

We report on a new technique of dissection of the nipple-areola-complex (NAC) in nipple-sparing mastectomy (NSM). NACs removed due to the presence of tumor cells beneath them were histologically examined for the presence of normal breast glandular tissue. Cases were divided into cohort 1, where NACs were dissected by sharp isolation, coring the nipple, and cohort 2, where the same procedure was preceded by hydrodissection of the areola. In 20 (17.4%) cases the planned NSM was converted to skin-sparing mastectomy (SSM) because of intraoperative findings of cancer in retro-areolar tissue. Histological examination of 20 NSMs converted to SSM showed the presence of glandular tissue in 12 out of 13 cohort 1 cases (92%) and in 1 out of 7 cohort 2 cases (14%). We conclude that hydrodissection creates a subdermal plane facilitating NAC dissection and permitting a more complete removal of breast tissue in NSM. Such radicality could prove important in the treatment of breast cancer and in BRCA 1-2 mutation carriers because of its potential for reducing the risk of relapse.

18FDG-PET evaluation correlates better than CT with pathological response in a metastatic colon cancer patient treated with bevacizumab-based therapy.

Around 20-30% of patients with hepatic metastasis from colorectal cancer can undergo liver resection, but the increased response rate obtained with the addition of monoclonal antibodies to chemotherapy regimens could result in a higher rate of liver surgery. In this report we describe the case of a patient who underwent a liver resection after neoadjuvant treatment with capecitabine, oxaliplatin and bevacizumab and who achieved a complete pathological response of the liver metastasis. A preoperative CT scan demonstrated a partial response to the treatment while 18FDG-PET scan correctly evaluated the complete pathological response in the liver and detected an active interaortocaval lymph node metastasis. New specific studies are required to evaluate the imaging response in metastatic colorectal cancer patients especially after treatment with new, targeted agents.