Nipple sparing mastectomy with prepectoral immediate prosthetic reconstruction without acellular dermal matrices: a single center experience.

BACKGROUND: Nipple-sparing mastectomy (NSM) with immediate prosthetic breast reconstruction (IPBR) is an oncologically accepted technique that allows to improve aesthetic results and patient quality of life. Traditionally, implant for reconstruction have been placed in a submuscolar (SM) plane, beneath the pectoralis major muscle (PMM). Recently, prepectoral (PP) placement of prosthesis is increasingly used in order to avoid morbidities related to manipulation of PMM. The aim of the present study was to report our experience with 209 NSMs and IPBR using a prepectoral approach and polyurethane-coated implant without acellular dermal matrices (ADMs). METHODS: A retrospective review of breast cancer patients who underwent NSM followed by PP - IPBR from January 2018 to April 2021 was performed. Data were recorded in order to evaluate operative details, major complications and oncological outcomes. Aesthetic results and patient quality of life were measured by a specific "QOL assessment PRO" survey. RESULTS: Two hundred and nine patients (269 breasts) with PP - IPBR after NSM were included. Mean age was 47 (25-73) years and median follow-up was 14 (1-40) months. A simultaneous contralateral implant-based mammoplasty of symmetrization after unilateral NSM was carried out in six of 149 (4%) patients. Implant loss was observed in three of 209 patient (1.44%); two of 209 (0.96%) patients developed a full-thickness NAC necrosis that required excision. During follow-up one local relapse (0.48%) and two regional nodes recurrences (0,96%) was observed. Patient satisfaction, assessed using a personalized QOL Assessment PRO survey, in term of aesthetic results, chronic pain, shoulder dysfunction, sports activity, sexual and relationship life and skin sensibility, was excellent. CONCLUSIONS: Our experience shows that PP-IPBR using polyurethane-coated implant after NSM is a safe, reliable and effective alternative to traditional IPBR with excellent aesthetic outcomes and high patient quality of life; it is easy to perform, minimizes complications related to manipulation of PPM and reduces operative time while resulting also in a cost-effective technique.

Surgical management of BRCA pathogenic variant carriers with breast cancer: a recent literature review and current state of the art.

Surgical management of breast cancer patients carrying pathogenic variants (PV) on breast cancer genes (BRCA) 1 and 2 has changed throughout the last decade due to growing availability of genetic testing, and has shifted towards the diffusion of bilateral mastectomy. Today's scenario however is in further evolution because of emerging data that suggest a personalized modulation of treatment. In this work we aimed to gather recent evidence supporting a prophylactic or conservative surgical approach in order to define the state of the art in today's treatment of BRCA carriers with breast cancer. We reviewed the literature to identify studies providing evidence on surgical treatment in breast cancer patients with BRCA 1 and 2 PVs. We included articles comparing outcomes between patients undergoing breast conserving surgery (BCS) and mastectomy, and articles investigating contralateral risk-reducing mastectomy (CRRM), with a particular focus on recent literature. International guidelines were also reviewed. Optimal surgical management of BRCA PV carriers with breast cancer remains controversial. While the introduction of routine genetic testing has initially led surgeons to favor more radical treatments, recent literature provides evidence that a conservative approach is safe and feasible in selected cases. Guidelines are heterogeneous and provide guidance without constraining the surgeon. Patients should undergo adequate genetic and surgical counseling in order to receive the best tailored surgical treatment. Because guidelines vary in different countries and provide no definite protocol, they highlight the importance of accurate surgical planning. Clinical, familial and psychosocial factors should be taken into account when approaching a BRCA PV carrier with breast cancer, in order to guarantee the best evidence-based patient care in an era of personalized treatment.

Hormone Receptor Expression Variations in Normal Breast Tissue: Preliminary Results of a Prospective Observational Study.

Normal breast tissue undergoes great variations during a woman's life as a consequence of the different hormonal stimulation. The purpose of the present study was to examine the hormonal receptor expression variations according to age, menstrual cycle, menopausal state and body mass index. To this purpose, 49 tissue samples of normal breast tissue, obtained during surgery performed for benign and malignant conditions, were immunostained with Estrogen (ER), Progesterone (PR) and Androgen receptors (AR). In addition, Ki67 and Gross Cystic Disease Fluid Protein were studied. The data obtained revealed a great variability of hormone receptor expression. ER and AR generally increased in older and post-menopausal women, while young women presented a higher proliferative rate, evaluated with Ki67. PR increase was observed in women with BMI higher than 25. The different hormonal receptor expression could favor the development of breast cancer.

Chromosome X aneusomy and androgen receptor gene copy number aberrations in apocrine carcinoma of the breast.

Carcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.

Methylation Profile of X-Chromosome-Related Genes in Male Breast Cancer.

Background: Androgen receptor (AR) has been described to play a prominent role in male breast cancer (MBC). It maps on chromosome X, and recent reports indicate that X-chromosome polysomy is frequent in MBC. Since the response to anti-androgen therapy may depend on AR polysomy and on its overexpression similarly to prostate cancer, the aim of the present study was to investigate the DNA methylation level of AR and its coregulators, especially those mapped on the X-chromosome, that may influence the activity of AR in MBC. Methods: The DNA methylation level of AR, MAGEA2, MAGEA11, MAGEC1, MAGEC2, FLNA, HDAC6, and UXT, mapped on the X-chromosome, was evaluated by quantitative bisulfite-NGS. Bioinformatic analysis was performed in a Galaxy Project environment using BWA-METH, MethylDackel, and Methylation Plotter tools. The study population consisted of MBC (41 cases) compared with gynecomastia (17 cases). Results: MAGEA family members, especially MAGEA2, MAGEA11, MAGEC, and UXT and HDAC6 showed hypomethylation of several CpGs, reaching statistical significance by the Kruskal-Wallis test (p < 0.01) in MBC when compared to gynecomastia. AR showed almost no methylation at all. Conclusions: Our study demonstrated for the first time that MAGEA family members mapped on the X-chromosome and coregulators of AR are hypomethylated in MBC. This may lead to their overexpression, enhancing AR activity.

Results obtained with level II oncoplastic surgery spanning 20 years of breast cancer treatment: Do we really need further demonstration of reliability?

Oncoplastic surgery (OPS) has demonstrated its superiority above traditional breast conserving surgery, but is still struggling to consolidate its role in breast cancer therapeutic protocols mainly because of contrasting scientific evidences and reduced follow-up results available. The objective of our contribution is to analyze results obtained with 381 patients consecutively treated in our Multidisciplinary Breast Center by means of level II OPS between January 1998 and January 2018 for unilateral, primary breast cancer. Surgical endpoints were mean specimen weight and volume, mean diameter of main lesion (MLD), rates of positive margins (PMR), re-excision (RR), conversion to mastectomy (CMR), complications (CR) and oncological endpoints as overall survival (OS), disease-free survival (DFS), and local recurrence rate (LR). About 29.1% were treated for multifocal/multicentric disease, and 29.1% previously underwent neo-adjuvant chemotherapy (NACT). Regarding surgical techniques, 53.0% of patients received "inverted T" and 30.1% "J" mammoplasties, whereas 13.6% underwent "round block," 2.3% "Grisotti," and 1% "batwing" techniques. Regarding surgical outcomes, mean specimen weight was 215 g (50-2157) and volume 345 mm3 (21-7980). MLD 23 mm, PMR 7.6%, RR 3.6%, CMR 1.6%, and CR 5.8%. With a mean follow-up of 118 months, oncological outcomes were: OS 93.7%, DFS 82.3%, LR 4.4%. In conclusion, our analysis confirmed level II OPS reliability even for longer follow-up timing and in difficult situations as multifocal disease or after NACT.

Incidence and Impact of Variant Celiacomesenteric Vascularization and Vascular Stenosis on Pancreatic Surgery Outcomes: Personal Experience.

Ischemic complications after pancreatic surgery can raise postoperative mortality from 4 to 83 per cent. Variants in vascular anatomy play a major role in determining such complications, but they have been only occasionally reported in the literature. We retrospectively analyzed 100 records of patients consecutively treated between January 2011 and December 2013 for resectable malignant diseases who underwent pancreaticoduodenectomy (PD) or total pancreatectomy to state the statistical impact of anatomical vascular variations in surgical outcomes (mean surgical timing, mean blood loss during surgery, and postoperative major complications onset) and to state whether preoperatively undetected vascular anomalies (VA) can raise the risk of postoperative ischemic complications. PD was performed in 89 patients, requiring multiorgan resections in three cases and total pancreatectomy was performed in 11 cases, which was associated to splenectomy in four patients. Incidence of VA was 25/100 (25%), whereas in 18/25 cases (72%) they were detected by preoperative radiologic setting. Their presence in patients undergoing PD significantly raised mean surgical timing (P = 0.003) and increased mean blood loss (P < 0.0001). Preoperatively undetected VA resulted in a major risk of postoperative acute liver ischemia (P = 0.008). Celiacomesenteric aberrant anatomy was proven to be related to an increased risk of intraoperative complications. If undetected preoperatively, they can be associated with anastomotic complications and liver failure. Maximal efforts must be done to detect and to preserve vascular anatomy of celiacomesenteric district.

Integrated breast cancer surgical treatment: novel aspects of minimally-invasive treatments.

The surgical management of breast cancer has been undergoing continuous and profound changes over the last 40 years. The evolution from aggressive and mutilating treatment to conservative approach has been long but constant, despite the controversies arising every time a new procedure came to light. Today, the esthetic satisfaction of breast cancer patients coupled with oncological safety is the goal of the modern breast surgeon. Breast-conserving surgery with adjuvant radiotherapy is considered the gold standard approach for patients with early stage breast cancer and the recent introduction of "oncoplastic techniques" has furtherly increased the use of breast-conserving procedures. Mastectomy still remains a valid surgical alternative in selected cases and is usually associated with immediate reconstructive procedures. New surgical procedures called "conservative mastectomies" are emerging as techniques that combine oncological safety and esthetic outcome by entirely removing the breast parenchyma sparing the breast skin and nipple-areola complex. Staging of the axilla has also gradually evolved toward less aggressive approaches with the adoption of sentinel node biopsy and new therapeutic strategies are emerging in patients with a pathological positivity in sentinel lymph node biopsy. The present special article will highlight the new surgical treatment options, which are more and more effective and respectful of breast cancer patients.

Improved outcomes for rectal cancer in the era of preoperative chemoradiation and tailored mesorectal excision: a series of 338 consecutive cases.

Neoadjuvant chemoradiation (CRT), tailored mesorectal excision, and intraoperative radiotherapy (IORT) have become the leading measures for rectal cancer treatment. The objective of this study was to evaluate early and long-term results of a multimodal treatment model for rectal cancer followed by curative surgery. Prospectively collected hospital records of 338 patients surgically treated for rectal cancer between January 1998 and December 2008 were retrospectively reviewed. Patients with high rectum level cancers and those with middle and low rectum cancers with clinical stage T1 to T2 underwent surgery, whereas those with T3 to T4 and N+ disease at the middle and low rectum received neoadjuvant CRT in 96.2 per cent of cases. Short-course neoadjuvant radiotherapy was not considered for neoadjuvant treatment. Postoperative major complications and mortality rates were 12.7 and 2.3 per cent, respectively. Overall 5-year disease-specific and disease-free survival were 80 and 73.1 per cent, respectively, whereas local recurrence rate was 6.1 per cent. At multivariate analysis, nodal status and circumferential margin status were independently associated with poor survival; local recurrence rates were independently affected by nodal and marginal status and tumor stage. The extent of mesorectal excision should be tailored depending on tumor location and the use of neoadjuvant chemotherapy, combined with IORT in advanced middle and low rectal cancer, leading to remarkable tumor downstaging with excellent prognosis in responding patients.

Locally recurrent rectal cancer: prognostic factors and long-term outcomes of multimodal therapy.

BACKGROUND: Pelvic recurrent rectal cancer is still a challenging clinical problem, and patients generally have a dismal prognosis and a poor quality of life. Surgical resection represents the only potentially curative treatment; neoadjuvant treatments are presently being taken into consideration to increase the resectability rate and to improve long-term survival. METHODS: Among 157 patients observed with recurrent rectal cancer, a series of 58 patients who underwent surgical exploration with curative intent for isolated local recurrence at a single referral institution was retrospectively analyzed. Demographic, pathologic, and therapeutic factors were evaluated to assess long-term prognosis and local control. RESULTS: Forty-four (75.9%) of 58 patients underwent surgical resection. The overall 5-year survival rate for patients who underwent surgical resection was 54.2%, whereas none of the unresected patients lived 5 years (P < 0.001). Patients with R0 resection showed a statistically higher 5-year overall survival and local control rate (72.4 and 70.2%, respectively) compared to R1 patients (37.5 and 31.2%, respectively). At multivariate survival analysis, feasibility of a surgical resection and radicality of excision proved to be independent positive prognostic factors. In contrast, increased presalvage carcinoembryonic antigen serum levels, back pain at diagnosis, and an increasing degree of fixation of recurrent disease to the pelvic wall at preoperative computed tomographic scan were statistically significantly linked to decreased overall survival. Preoperative chemoradiation and radicality of the surgical excision independently influenced the local control among surgically resected patients. CONCLUSIONS: Surgical resection still remains the most important therapeutic and prognostic factor for patients with locally recurrent rectal cancer. Multimodal treatments can be safely performed by an experienced team in referral tertiary centers and can result in a safer outcome, better local disease control, and even long-term survival in carefully selected patients.