Review: Implant-Based Breast Reconstruction After Mastectomy for Breast Cancer: A Meta-analysis of Randomized Controlled Trials and Prospective Studies Comparing Use of Acellular Dermal Matrix (ADM) Versus Without ADM.

BACKGROUND: Breast cancer is the world's most prevalent cancer, and many breast cancer patients undergo mastectomy as the choice of treatment, often with post-mastectomy breast reconstruction. Acellular dermal matrix (ADM) use has become a method to improve outcomes of reconstruction for these patients. We aimed to compare postoperative complications and patient-reported outcomes, which are still poorly characterized, between groups utilizing acellular dermal matrix during reconstruction and those without. MATERIALS AND METHODS: We searched electronic databases from inception to 16 June 2022 for randomized controlled trials and prospective cohort studies comparing the outcomes of patients who have and have not received acellular dermal matrix in implant-based breast reconstruction. The results were quantitatively combined and analyzed using random-effects models. RESULTS: A total of nine studies were included, representing 3161 breasts. There was no significant difference in postoperative outcomes, such as seroma formation (p = 0.51), hematomas (p = 0.20), infections (p = 0.21), wound dehiscence (p = 0.09), reoperations (p = 0.70), implant loss (p = 0.27), or skin necrosis (p = 0.21). Only two of the studies included evaluated patient-reported outcomes between the use and non-use of ADM in implant-based breast reconstruction using BREAST-Q questionnaire, as well as self-reported pain. There was no reported significant difference in BREAST-Q or pain scores. CONCLUSIONS: This meta-analysis shows comparable short- and long-term outcomes between ADM and non-ADM breast reconstruction, suggesting that the use of ADM may not be necessary in all cases given their additional cost. However, there is a paucity of data for patient-reported outcomes, and further research is required to determine whether ADM use affects patient-reported outcomes.

Extensive Characterization of Mesenchymal Stem Cell Marker Expression on Freshly Isolated and In Vitro Expanded Human Adipose-Derived Stem Cells from Breast Cancer Patients.

Variation in numbers and functions of cells in fat tissues may affect therapeutic outcomes and adverse events after autologous fat tissue grafting in postmastectomy breast cancer patients; however, the relevant information regarding cellular components is still incomplete. Phenotypic characterization of heterogeneous cell subsets in stromal vascular fraction (SVF) isolated from fat tissues by flow cytometry was also limited to a combination of few molecules. This study, therefore, developed a polychromatic staining panel for an in-depth characterization of freshly isolated SVF and expanded adipose-derived stem cells (ADSC) from the patients. ADSC were found predominant in SVF (~65% of CD45- cells) with a homogenous phenotype of CD13+CD31-CD34+CD45-CD73+CD90+CD105-CD146- (~94% of total ADSC). Endothelial progenitor cells (EPC) and pericytes were minor (~18% and ~11% of CD45- cells, respectively) with large heterogeneity. Downregulation of CD34 and upregulation of CD105 in ADSC were profound at passage 3, showing a phenotype similar to the classical mesenchymal stem cells from the bone marrow. Results from this study demonstrated that fat tissue collected from patients contains ADSC with a highly homogenous phenotype. The in vitro culture of these cells maintained their homogeneity with modified CD34 and CD105 expression, suggesting the expansion from a single population of ADSC.

Nomogram to predict non-sentinel lymph node status using total tumor load determined by one-step nucleic acid amplification: first report from Thailand.

BACKGROUND: Axillary staging is a significant prognostic factor often used to determine the treatment course for breast cancer. One-step nucleic acid amplification (OSNA) is now the most accepted method for intra-operative assessment of sentinel lymph nodes (SLN) as it can semi-quantitatively determine the tumor burden in these SLN. Axillary lymph node dissection (ALND) may be omitted in patients with limited disease in the axilla. The objective was to create nomogram for prediction of non-sentinel lymph node (NSLN) status using OSNA to avoid unnecessary ALND. PATIENTS AND METHODS: Patients with invasive breast cancer T1-T3 and clinically negative axillary lymph nodes underwent SLN biopsy assessed by OSNA. The patients with positive SLN underwent ALND. Correlations between total tumor load (TTL), clinicopathological parameters, and NSLN status were analyzed by Chi square statistic and logistic regression. Model discrimination was evaluated using receiver-operating characteristic (ROC) analysis. RESULTS: The total number of patients who underwent SLN biopsies was 278. There were 89 patients with positive SLN. NSLNs were positive in 40 patients. Larger tumor size, presence of lymphovascular invasion (LVI) and higher log TTL were independent factors that predicted positive NSLN. TTL can discriminate NSLN status with area under the ROC curve of 0.789 (95% CI 0.686-0.892). Two nomograms using different parameters obtained pre- and post-operatively can predict NSLN involvement with better area under the ROC curve (0.801, 95% CI 0.702-0.900 and 0.849, 95% CI 0.766-0.932, respectively). CONCLUSIONS: Nomograms using results obtained via OSNA can predict NSLN status, as well as aid in deciding to omit the use of ALND.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Surgeons' Recommendation is the Factor in Determining the Breast Cancer Surgery Procedures: an Experience from Rural Hospital in Thailand

Introduction: The majority of breast cancer patients in rural hospital in developing countries still warrant for total mastectomy. Surgeon advice regard surgical procedure is one of the most important factors in decision making. Our study aims to compare the rate of breast-conserving surgery (BCS), mastectomy (MT) and mastectomy with immediate breast reconstruction (MTIBR) between the surgeons who offer only MT (group A) and who offer BCS MT and MTIBR (group B). Method: A retrospective cohort study was conducted at Ratchaburi hospital, Thailand from January 2010 to April 2014. We categorized patients into 2 groups (group A and B). Univariated analysis was selected to determine the factors that associated with the breast surgery procedures. Results: From January 2010 to April 2014, we recruited 310 breast cancer patients, 221 patients (71.2%) were treated by surgeons in group A, 89 patients (28.7%) by surgeons in group B. The choice of breast surgery is significantly different between 2 groups (P<0.001). In group A, 213 (96.3%) patient had MT and only 3 (1.3%) BCS and 5 (2.2%) MTIBR. Whilst in group B, 58 (65.1%) patient had MT and 11 (12.3%) BCS and 20(22.4%) MTIBR. Choice of breast surgery in patients with stage 1,2,3 are significantly different between 2 groups (P=0.004, <0.001, 0.025 respectively). Age is the only factor that significantly affects the choice of surgery in the group B but not in group A. Conclusion: Surgeon's competency and comprehensive preoperative consultation by offering BCS, MT and MTIBR can affect the choice of surgical procedure for breast cancer patient.

Conservative mastectomy versus nipple-sparing mastectomy: preliminary considerations of oncological safety on 30 patients not receiving intra-operative radiotherapy.

BACKGROUND: For several years, there has been broad consensus that nipple-sparing mastectomy is a safe surgical treatment for breast cancer. However, the technique is associated with a relatively high risk of local recurrence (LR) behind the nipple-areola complex (NAC). It is for this reason that some years ago we introduced intraoperative radiotherapy with electrons (ELIOT) targeted specifically to the NAC to reduce the probability of recurrence there. However, in some cases we preferred to avoid ELIOT when the NAC appears to have a poor blood supply to ensuring the best chance of NAC survival. METHODS: From July 2003 to April 2010 at our institute, 30 patients received nipple-sparing mastectomy but neither ELIOT nor external radiotherapy, as the surgeon considered the irradiation would markedly compromise the chances of NAC survival, because of sub-optimal vascularization. RESULTS: After a median follow-up of 5 years there were no LRs with minor post-operative complications. CONCLUSIONS: This preliminary case series indicates that the presented technique can be a safe procedure in breast cancer surgery, but requires greater number of cases and a longer follow-up to confirm the oncological safety.

Giant benign phyllodes tumor with lactating changes in pregnancy: a case report.

BACKGROUND: Phyllodes tumor in pregnancy is extremely rare. We present the first case ever reported of a giant benign phyllodes tumor with lactating changes during pregnancy. PRESENTATION OF CASE: A 36-year-old female patient at the 32nd week of pregnancy presented with a huge mass in left breast for 5-6 months. Physical examination revealed a firm palpable 20 cm mass occupying the whole left breast. Ultrasound guided core needle biopsy demonstrated a fibroepithelial lesion suggestive of benign phyllodes tumor. She was scheduled for mastectomy three weeks after birth delivery. The microscopic examination of the resected specimen revealed the mass consisted mainly of lactating components with areas of hypercellular stroma and epithelial proliferation in leaf-like pattern. Finally, the pathological report confirmed a giant benign phyllodes tumor with lactating changes and frees all surgical margins. DISCUSSION: Phyllodes tumor in pregnancy is rare with just nine cases reported. It is unknown if the rapidly growing mass in pregnant patient is hormone-dependent. This is the first report of a giant benign phyllodes tumor with lactating changes in pregnant patient. In these large phyllodes tumors, heterogeneous stromal components are common. It is occasionally difficult to distinguish between benign phyllodes tumor with lactating changes and lactating adenoma. Because the surgical treatment and local recurrence rate are different between these two diseases, we need to clearly differentiate benign phyllodes tumors from other benign breast diseases. CONCLUSIONS: This case emphasizes the heterogeneity of giant phyllodes tumors. Therefore, it is important to thoroughly examine the resected specimen for possible additional components. The key point is that adequate and clear surgical margins in any phyllodes tumors must be achieved to reduce local recurrence.

Nipple sparing mastectomy: does breast morphological factor related to necrotic complications?

BACKGROUND: Nipple sparing mastectomy (NSM) can be performed for prophylactic mastectomy and the treatment of selected breast cancer with oncologic safety. The risk of skin and nipple necrosis is a frequent complication of NSM procedure, and it is usually related to surgical technique. However, the role of the breast morphology should be also investigated. METHOD: We prospectively performed an analysis of 124 NSM from September 2012 to January 2013 at the European Institute of Oncology, Milan, Italy, focusing on necrotic complications. We analyzed the association between the risks of skin necrosis and the breast morphology of the patients. RESULTS: Among 124 NSM in 113 patients, NSM procedures were associated with necrosis in 22 mastectomies (17.7%) among which included partial necrosis of nipple-areolar complex (NAC) in 15 of 124 NSM (12.1%) and total necrosis in 4 cases (3.5%). The NAC was removed in 5 NSM cases (4%). The volume of breast removed was the only significant factor increasing the risk of skin necrosis. The degree of ptosis was not significantly related to the necrosis risk. CONCLUSIONS: Large glandular specimen increases the risk of NAC necrosis. The degree of ptosis and the distance between the sternal notch and the NAC have no significant impact on necrotic complications in NSM. To reduce the necrotic complications in large breast after NSM, reconstruction should better be performed with autologous flap or slow skin expansion using the expander technique.

Axillary web syndrome self-assessment questionnaire: Initial development and validation.

INTRODUCTION: Despite the great strides made in medical knowledge, surgery still remains a necessary part of the breast cancer treatment. Surgical procedures still lead to post surgical sequelae. The axillary web syndrome (AWS) is one such sequela, which can lead to disability, reduced arm mobility and compromised quality of life. It is often unidentified and the literature regarding its assessment is limited. To improve diagnosis and patient education, the Screening Test AWS (ST-AWS) questionnaire was drafted and applied at the European Institute of Oncology (EIO). MATERIALS AND METHOD: We prospectively recruited patients from October 2012 to December 2012. Patients who underwent sentinel lymph node biopsy and/or axillary dissection procedures were registered. Physical examination was set as a gold standard. RESULTS: 88 patients completed the questionnaire. Among these, 32 patients had axillary web syndrome diagnosed, thus a 36% incidence. The questionnaire achieved a sensitivity of 94%, a specificity of 91%, a positive prevalence value (PPV) of 86%, a negative prevalence value (NPV) of 96% and an accuracy of 92%. CONCLUSION: Our questionnaire achieves high sensitivity and predictive values, and we would recommend it as a screening-tool for auto-diagnosis of the AWS. The main objective of the questionnaire is to enhance patient and therapist awareness of the problem, and prompt management to shorten the effects of this disability. Moreover, it may offer a tool to enhance body image acceptance after surgery. Further studies whereby the efficacy of the questionnaire is investigated in a larger, heterogeneous group and in different situations are warranted.

International oncoplastic breast surgery training.

Breast cancer mortality is being dramatically reduced in past decades. Breast cancer survivors are seeking their quality of lives after treatment along with effective and curative oncological control. Surgical options both on ablative and reconstructive purpose procedures are more widely performed in different techniques, making the breast cancer surgery becoming an individualized or tailoring surgery. Multidisciplinary team approach in breast cancer is becoming a standard practice. Training in oncoplastic breast surgery will improve the quality of breast cancer patient care. International program should be established to develop collaboration in academic and science all over the globe.

Bilateral breast reconstruction with bipedicle transverse rectus abdominis myocutaneous (TRAM) flap for simultaneous delayed and immediate breast reconstruction after therapeutic modified radical mastectomy and prophylactic nipple sparing mastectomy.

Contralateral prophylactic mastectomy (CPM) rate is increasing worldwide recently due to better understanding of genetic and hereditary breast cancer. The evolution of mastectomy technique from modified radical mastectomy to nipple sparing mastectomy with immediate or delayed breast reconstruction is also a potential cause of increasing mastectomy rate. This case report presents a young woman who had breast cancer at very young age then she decided for CPM due to her sister and mother are also breast cancer victim. We report clinical course and immediate outcome of the oncologic and reconstructive surgery in this case.

Stem cell and tissue engineering in breast reconstruction.

Breast cancer worldwide is the most common cancer in women with incidence rate varying from geographic areas. Guidelines for management of breast cancer have been largely established and widely used. Mastectomy is one of the surgical procedures used treating breast cancer. Optionally, after mastectomy, appropriately selected patients could undergo breast reconstruction to create their breast contour. Many techniques have been used for breast reconstructive surgery, mainly implant-based and autologous tissue reconstruction. Even with highly-experienced surgeon and good-quality breast and autologous substitute tissue, still there could be unfilled defect after mastectomy with reconstruction. Stem cell, in particular, adipose-derived stem cell residing within fat tissue, could be used to fill the imperfection providing optimal breast shape and natural feeling of fat tissue. However, whether surgical reconstruction alone or in combination with stem cell and tissue engineering approach be used, the ultimate outcomes are patient safety first and satisfaction second.

Metabolic syndrome and outcome after breast reconstruction.

Metabolic syndrome with its core components including obesity, insulin resistance, dyslipidemia and hypertension; is has been proven as a multiplex risk factor for cardiovascular disease. It is also recently shown by meta-analysis for its association with increased risk of common cancers including breast cancer. Multiple studies have shown metabolic syndrome prone to have poor perioperative outcome and complications for multiple type of surgery including vascular and flap surgery due to compromising microvascular circulation in this group of patient. However, lack of data on consequences of metabolic syndrome on breast cancer surgery as well as in breast reconstructive surgery indicate the need of further study in this area for the improvement of outcome of breast cancer and reconstructive surgery.

Platysma myocutaneous flap interposition in surgical management of large acquired post-traumatic tracheoesophageal fistula: A case report.

INTRODUCTION: Acquired post-traumatic tracheoesophageal fistula (TEF) is an uncommon entity requiring early diagnosis. Among the many strategies in surgical management, we report a case successfully treated with a single-stage tracheal resection and esophageal repair with platysma myocutaneous interposition flap. PRESENTATION OF CASE: A 24-year-old man had a motor vehicle accident with head injury and cerebral contusion who required mechanical ventilation support. Three weeks later, he developed hypersecretion, and recurrent episodes of aspiration pneumonia. The chest computed tomography, esophagogastroduodenoscopy, and bronchoscopy revealed a large TEF diameter of 3cm at 4.5cm from carina. Single-stage tracheal resection with primary end-to-end anastomosis and esophageal repair with platysma myocutaneous interposition flap was performed. A contrast esophagography was done on post-operative day 7 and revealed no leakage. He was discharged on post-operative day 10. Esophagogastroduodenoscopy at 1 month revealed patient esophageal lumen. At present he is doing well without any evidence of complications such as esophageal stricture or fistula. DISCUSSION: There are many choices of myocutaneous muscle flaps in trachea and esophageal closure or reinforcement. The platysma myocutaneous flap interposition is simple with the advantage of reduced bulkiness. Concern on the vascular supply is that flap should be elevated with the deep adipofascial tissue under the platysma to ensure that the flap survival is not threatened. CONCLUSION: The treatment of acquired TEF with platysma myocutaneous flap is an alternative procedure for a large uncomplicated TEF as it is effective, technically ease, minimal donor site defect and yields good surgical results.

Incidence, predictive factors, and prognosis for winged scapula in breast cancer patients after axillary dissection.

PURPOSE: Axillary lymph node dissection is part of breast cancer surgery, and winged scapula is a possible sequela. Data regarding its incidence, predictive factors, and patient prognosis remains inconsistent. Ignorance of its diagnosis may lead to undertreatment with physical morbidity. METHODS: Breast cancer patients with axillary lymph node dissection were prospectively recruited. Postoperative examinations by the physiotherapy staff were performed. RESULTS: One hundred eighty-seven patients were recruited during July-October 2012; 51 patients had a positive diagnosis (27.2 %), with 38 patients (86 %) who recovered completely from the winged scapula, while 6 patients (13 %) still had winged scapula at 6 months after surgery. One hundred thirty patients underwent mastectomy and 100 cases had immediate reconstruction. Age, BMI, previous shoulder joint morbidity, and breast surgery were not associated with winged scapula. Neoadjuvant treatment, mastectomy or conservative surgery, immediate reconstruction, tumor size, and nodal involvement also did not show any correlation. Breast reconstruction with prosthesis, even with serratus muscle dissection, does not increase the incidence of winged scapula. CONCLUSION: Winged scapula is not an uncommon incidence after breast cancer surgery. Physiotherapy is related to the complete recovery. The severity or grading of the winged scapula and the recovery time after physiotherapy should be investigated in the future studies.

Vascular endothelial growth factor ­634G/C polymorphism is associated with increased breast cancer risk and aggressiveness.

Polymorphisms in the promoter and 5' untranslated region of vascular endothelial growth factor (VEGF) have been associated with VEGF levels. To investigate the role of VEGF polymorphisms in breast cancer, the VEGF ­2578C/A, ­1498C/T, ­1154G/A and ­634G/C polymorphisms were genotyped in 483 breast cancer patients and 524 healthy controls. VEGF mRNA levels in breast cancer tissue were determined using semi­quantitative RT­PCR. The genotypes, ­634G/C and ­634C/C, were associated with an increased risk for breast cancer when compared with the ­634G/G genotype. The VEGF ­634G/C genotype was associated with tumor size >20 mm, perineural invasion and stage II­IV. Individuals with ­634C/C had lower disease­free survival. Patients with the VEGF ­634C/C genotype exhibited the highest VEGF mRNA levels. High VEGF mRNA expression correlated with tumor size >20 mm, presence of lymphovascular invasion and axillary nodal metastasis. These observations suggested that VEGF ­634G/C polymorphisms have a significant role in breast cancer susceptibility and aggressiveness.

Immediate breast reconstruction with expander in pregnant breast cancer patients.

BACKGROUND: Breast reconstruction after mastectomy is currently considered an essential component in managing breast cancer patients, particularly those diagnosed at a young age. However, no studies have been published on the feasibility of immediate breast reconstruction in patients diagnosed and operated during the course of gestation. METHOD: We retrospectively identified all breast cancer patients who were subjected to mastectomy and immediate breast reconstruction during pregnancy at the European Institute of Oncology between 2002 and 2012. Patient demographics, gestational age at surgery, tumor stage, adjuvant treatment, details of the surgical procedures, surgical outcomes and fetal outcomes were analyzed. RESULTS: A total of 78 patients with breast cancer diagnosed during pregnancy were subjected to a surgical procedure during the course of gestation. Twenty-two patients had mastectomy; of whom 13 were subjected to immediate breast reconstruction. Twelve out of 13 patients had a two-stage procedure with tissue expander insertion. Median gestational age at surgery was 16 weeks. No major surgical complications were encountered. Only one patient elected to have an abortion, otherwise, no spontaneous abortions or pregnancy complications were reported. Median gestational age at delivery was 35 weeks (range: 32-40 weeks). No major congenital malformations were reported. At a median follow-up of 32 months, all patients are alive with no long-term surgical complications. CONCLUSIONS: This is the first study of immediate breast reconstruction in pregnant breast cancer patients. Tissue expander insertion appears to ensure a short operative time, and does not seem to be associated with considerable morbidity to the patient or the fetus. Hence, it could be considered in the multidisciplinary management of women diagnosed with breast cancer during pregnancy.

Locoregional recurrence in patients with HER2 positive breast cancer.

Literature shows that HER2/neu positive breast cancer cells are more sensitive to radiation-induced apoptosis by targeting the epidermal growth factor receptor family tyrosine kinase. We selected 466 patients with pT1-2 HER2/neu positive tumors who received adjuvant trastuzumab for primary invasive breast cancer. Patients were divided into three groups [Quadrantectomy followed by conventional radiotherapy vs Quadrantectomy followed by Intra-operative radiotherapy with electrons vs Mastectomy without radiotherapy]. After a median follow-up of 52 months, the 5-year cumulative incidence of locoregional recurrence (LRR) was 1.9%, 11.5% and 5.0% respectively (p < 0.01). At the multivariate analysis, extensive perivascular invasion, Luminal B HER2/Progesterone Receptor (PgR) negative status and Quadrantectomy followed by Intra-operative radiotherapy with electrons have significantly increased the risk of LRR. Our results suggest that HER2/neu positive breast cancer might have better outcomes when treated simultaneously with external radiotherapy and trastuzumab. Moreover, we underline the importance of PgR and further new stratification of risk among luminal subtypes.

Do clinicopathological features of the cancer patient relate with nipple areolar complex necrosis in nipple-sparing mastectomy?

BACKGROUND: The selections of nipple-sparing mastectomy (NSM) are principally depending on oncologic indication and oncologic safety. The main complication of NSM is nipple areolar complex (NAC) necrosis, and it is usually related to surgical technique. However, the patients' clinicopathological factors should be also considered. METHOD: We retrospectively reviewed 934 consecutive NSM patients during 2002-2007 at the European Institute of Oncology, Milan, Italy. We identified a group of patient who had NAC excision because of NAC necrosis and compared this group with those who had successful NAC conservation. We analyzed the association between the risk of NAC necrosis and the clinicopathological features of the patients. RESULTS: Among 934 NSM, 772 were invasive cancers and 162 were in situ cancers. Of the 934, 40 NAC (4.2%) were removed during the postoperative period because of necrosis. When we considered age, BMI, menopausal status, smoking status, tumor size, axillary lymph node status, in situ or invasive cancer histology, presence of extensive situ component, grading, estrogen receptor, progesterone receptor, HER2/neu overexpression, Ki-67 proliferative index, and peritumoral vascular invasion, no association was observed between patients' clinicopathological features and NAC necrosis incidence. CONCLUSIONS: In our study, clinicopathological features have no significant impact on necrosis complication in therapeutic NSMs. Positive retroareolar margin is the risk of necrosis. Further studies are required to avoid bias due to the different cancer treatments such as different reconstruction techniques and intraoperative radiation protocols. The correlation between breast morphology and NAC necrosis should also be investigated in the future.