Background: The deep inferior epigastric perforator (DIEP) flap has become a popular option for breast reconstruction because of reduced donor-site morbidity. As the number of perforators per flap is reduced, vascular compromise may develop. Venous congestion can occur despite patent primary venous anastomosis. Methods: A prospective series of 100 consecutive DIEP flaps in breast reconstruction were studied for vascular problems and outcomes. Results: Ninety-nine flaps were successful. No arterial compromise occurred. Overall, venous congestion occurred in 15 flaps. Eleven flaps developed intraoperative venous congestion, but only five flaps required vascular bypass between the superficial epigastric vein and chest wall vein for additional drainage. One flap was lost because of the authors' failure to recognize and manage inadequate venous outflow by the chosen perforator vein. One flap suffered major fat necrosis because of postoperative thrombosis of the saphenous vein bypass. Overall, fat necrosis occurred in 12 flaps. Conclusions: DIEP venous congestion, despite patent primary venous anastomosis, occurs in 5 percent of these flaps and can be managed successfully by a second venous bypass between the superficial epigastric vein and any chest wall vein. Failure to recognize and manage this can cause flap loss.
Coverage of complex perineal wounds resulting from surgical and radiation therapy results in significant morbidity. Acute complications occur in 25% to 60% of patients. Serious complications occur in 25% to 46% of patients. Musculocutaneous or omental flaps are used as primary or salvage procedures for nonhealing perineal wounds. Vertical rectus abdominis flaps are ideally suited to bring nonirradiated tissue into defects associated with radical surgical extirpation procedures and irradiated fields.A retrospective review of 73 cases using a vertical rectus abdominis flap for perineal reconstruction is reported. Acute perineal wound complications occurred in 17.8%, while serious complications requiring reoperation occurred in only 3.5%. There was 1 complete flap failure. Primary healing occurred in 84.9% of patients, with 94.5% of patients obtaining a healed perineal wound within 30 days. These results support the use of the transpelvic vertical rectus flap in difficult perineal wound reconstruction.
Abstract The tissue adjacent to breast tumors has been referred to as “normal-like” tissue despite exhibiting many alterations at epigenetic and gene expression levels consistent with enhanced proliferation and wound healing signatures. However, the influence of such alterations on the proliferation and differentiation of healthy breast progenitors is currently unknown. Fibroblasts are a major component of microenvironment for the healthy and malignant breast cells. We therefore, isolate fibroblast from primary breast tumors, tissue adjacent to tumors (TAT) and the healthy breast tissue and examine their ability to support proliferation of healthy and malignant breast cells. To characterize the TAT samples we first utilized clonal co-culture assays using breast cells obtained from the healthy breast tissue (reduction mammoplasty sample, RM) and the healthy fibroblasts. Our results suggested that the TAT samples surprisingly contained significantly decreased pool of progenitors compared to the RM samples. In order to study the underlying mechanism, we characterized fibroblasts derived from either the breast tumours (TAFs) or the TAT samples (TATF) or the RM normal samples (NAFs) and assessed their role on breast progenitor cell functions. Fibroblasts were isolated from the ER+ and ER- breast tumours and their adjacent breast tissue. We observed that matrigel co-cultures consisting of RM samples and NAFs led to a 5.5-fold expansion of the progenitors, whereas the co-cultures of TAT or the RM samples with either TAFs or TATFs failed to show expansion of epithelial progenitors. The comparative secretome analysis of the NAFs and the TATFs identified TGFβ as a candidate molecule primarily secreted only by the TATFs and not by NAFs. Interestingly, blocking TGFβ signaling restored both TAFs' and TATFs' ability to support the expansion of healthy progenitors in matrigel cultures. Lastly, we found that TAFs were able to enhanced breast cancer cell proliferation in vivo and in vitro but to a lesser extent than the TAFs. Our observations suggest that the tissues adjacent to breast tumours are transformed into a TGFβ-enriched environment that is supportive of breast tumour growth while suppressing the proliferation and differentiation potentials of the healthy breast progenitors. Our data also suggest that the use of TGFβ blockers may be important in reducing risk of local breast tumour recurrence. Citation Format: Chatterjee S, Berdnikov A, Lee-Wing V, Safneck J, Buchel E, Raouf A. Fibroblasts isolated from the “normal-like” tissue adjacent to breast tumours suppress healthy epithelial progenitor cell proliferation while supporting tumour cell growth [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-03-11.
Human breast cancer cells are known to activate adjacent "normal-like" cells to enhance their own growth, but the cellular and molecular mechanisms involved are poorly understood. We now show by both phenotypic and functional measurements that normal human mammary progenitor cells are significantly under-represented in the mammary epithelium of patients' tumor-adjacent tissue (TAT). Interestingly, fibroblasts isolated from TAT samples showed a reduced ability to support normal EGF-stimulated mammary progenitor cell proliferation in vitro via their increased secretion of transforming growth factor β. In contrast, TAT fibroblasts promoted the proliferation of human breast cancer cells when these were co-transplanted in immunodeficient mice. The discovery of a common stromal cell-mediated mechanism that has opposing growth-suppressive and promoting effects on normal and malignant human breast cells and also extends well beyond currently examined surgical margins has important implications for disease recurrence and its prevention.
The scratch assay is an in vitro assay that allows for high-throughput quantification of wound closure by keratinocytes and fibroblasts with relative ease. However, this assay is amenable to experimental variables, which can result in false-positive and false-negative data, making the interpretation of such data difficult. Also, data variability decreases the sensitivity of the scratch assay. Here, we identify important sources of data variation in the scratch assay and provide rational mitigation strategies that enable robust and highly reproducible quantification of scratch width and area, and ultimately the scratch closure rates. By eliminating these sources of variability, the sensitivity of the scratch assay is enhanced, thereby allowing for identification of dependent variables with wide-ranging impacts on wound closure in a robust and standardized manner.
Patients diagnosed with melanoma of the foot have been reported to have a poor prognosis. We reviewed our experience at a tertiary-care medical clinic to determine the disease course in patients diagnosed with melanoma of the foot.A retrospective review was performed of 38 patients with a diagnosis of primary or locally recurrent melanoma of the foot treated between January, 1988, and July, 2004. The main outcome measures included methods of diagnosis, clinical and histopathologic features, and patterns of recurrence.The mean age at diagnosis was 61 years; most were women (58%) and Caucasian (95%). The average time to diagnosis was 17 months. Initial clinical diagnosis had been considered benign in 12 (32%). The median Breslow thickness was 1.75 mm, T1 lesions were the most common, and acral lentiginous melanoma accounted for 42%. Thirteen patients (34%) had ulcerated lesions. Sentinel lymph node biopsy specimens of 25 patients identified four (16%) with metastatic disease. Surgical complications occurred in 12 patients, usually after skin graft or soft-tissue flap reconstruction. Systemic recurrence developed in six patients, four of whom also had regional recurrence.Most patients were elderly Caucasian women and most presented with early-stage disease, but diagnosis can be difficult and a subgroup presented with thick melanomas. Reconstructive surgical procedures had a high rate of complications; however, overall functional outcomes were good. Stage of cancer at diagnosis was associated with systemic metastases.
Autologous breast reconstruction has continued to evolve, with significant decreases in the abdominal-wall morbidity associated with these newer reconstructions. Recently, the superficial inferior epigastric artery (SIEA) flap has replaced the perforator flaps in the majority of the authors' autologous tissue breast reconstruction cases. They reported their series of 75 SIEA flaps for breast reconstruction with a discussion about the difficulties and limitations of using this specific flap.
