Stratification of Surgical Risk in DIEP Breast Reconstruction Based on Classification of Obesity.

BACKGROUND: From both a medical and surgical perspective, obese breast cancer patients are considered to possess higher risk when undergoing autologous breast reconstruction relative to nonobese patients. However, few studies have evaluated the continuum of risk across the full range of obesity. This study sought to compare surgical risk between the three World Health Organization (WHO) classes of obesity in patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: A retrospective review of 219 obese patients receiving 306 individual DIEP flaps was performed. Subjects were stratified into WHO obesity classes I (body mass index [BMI]: 30-34), II (BMI: 35-39), and III (BMI: ≥ 40) and assessed for risk factors and postoperative donor and recipient site complications. RESULTS: When examined together, the rate of any complication between the three groups only trended toward significance (p = 0.07), and there were no significant differences among rates of specific individual complications. However, logistic regression analysis showed that class III obesity was an independent risk factor for both flap (odds ratio [OR]: 1.71, 95% confidence interval [CI]: 0.91-3.20, p = 0.03) and donor site (OR: 2.34, 95% CI: 1.09-5.05, p = 0.03) complications. CONCLUSION: DIEP breast reconstruction in the obese patient is more complex for both the patient and the surgeon. Although not a contraindication to undergoing surgery, obese patients should be diligently counseled regarding potential complications and undergo preoperative optimization of health parameters. Morbidly obese (class III) patients should be approached with additional caution, and perhaps even delay major reconstruction until specific BMI goals are met.

Assessing Age as a Risk Factor for Complications in Autologous Breast Reconstruction.

BACKGROUND: Breast cancer is primarily a diagnosis of older women. Many patients seeking breast reconstruction are elderly women (aged 65 years or older). However, many surgeons anecdotally believe that surgery in elderly patients is inherently dangerous, or at least prone to more complications. METHODS: The authors conducted a retrospective cohort study composed of chart review of all deep inferior epigastric perforator flap breast reconstruction patients at a single institution divided into an elderly cohort (65 years or older) and a nonelderly cohort (younger than 65 years). Cohort was the primary predictor variable. Demographic and comorbidity data were secondary predictor variables. Primary outcomes were complete flap loss, partial flap loss, or need for flap reexploration. Secondary outcomes such as wound healing problems, seroma, and others were also assessed. RESULTS: There were 285 flaps in the nonelderly cohort and 54 flaps in the elderly cohort. The elderly cohort had higher rates of diabetes, hypertension, and hyperlipidemia. Chi-square analysis showed no significant differences in primary outcomes between the two cohorts. Breast wound dehiscence was significantly higher in the elderly cohort (p < 0.01). On logistic regression, being elderly was seen as a significant risk factor for complete flap loss (OR, 10.92; 95 percent CI, 0.97 to 122.67; p = 0.05). The overall success rate for the nonelderly cohort was 99.6 percent, whereas the success rate for the nonelderly cohort was 96.3 percent. CONCLUSIONS: Elderly women desire breast reconstruction. Free flap breast reconstruction is a viable and safe procedure in these patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Sandwiched White Adipose Tissue: A Microphysiological System of Primary Human Adipose Tissue.

White adipose tissue (WAT) is a critical organ in both health and disease. However, physiologically faithful tissue culture models of primary human WAT remain limited, at best. In this study we describe a novel WAT culture system in which primary human WAT is sandwiched between tissue-engineered sheets of adipose-derived stromal cells. This construct, called "sandwiched white adipose tissue" (SWAT), can be defined as a microphysiological system (MPS) since it is a tissue-engineered, multicellular, three-dimensional organ construct produced using human cells. We validated SWAT against the National Institutes of Health MPS standards and found that SWAT is viable in culture for 8 weeks, retains physiologic responses to exogenous signaling, secretes adipokines, and engrafts into animal models. These attributes position SWAT as a powerful tool for the study of WAT physiology, pathophysiology, personalized medicine, and pharmaceutical development.

Versatility of subscapular chimeric free flaps in the secondary reconstruction of composite posttraumatic defects of the upper face.

High energy injuries to the upper face present challenging reconstructive problems. In some cases, initial reconstructive efforts result in unfavorable outcomes that require secondary intervention. Chimeric free flaps based on the subscapular system offer the tissue components and volume needed for these complex reconstructions. This is a series of five patients who underwent secondary reconstruction of the middle and upper face following traumatic injury. Mechanism of injury, prior attempts at reconstruction, and characteristics of the tissue defects and the flaps used in their reconstruction are described. Two patients were female and three were male. Three injuries resulted from gunshot wounds, and two from motor vehicle accidents. All patients had multiple prior failed attempts at reconstruction using local/regional tissue. Defects included symptomatic oronasal or oro-orbital fistulas, enophthalmos, and forehead contour deformities. Two of the flaps used included scapular bone and latissimus muscular components, and three included scapular bone and thoracodorsal artery perforator-based skin paddle components. All free tissue transfers were successful, and no patients suffered significant complications. Chimeric free flaps based on the subscapular system offer a valuable secondary strategy for reconstruction of composite defects of the upper face when other options have been exhausted through previous efforts.

Treatment of submucous cleft palate with selective use of the Furlow Z-palatoplasty.

PURPOSE: Submucous cleft is an uncommon entity that can be complicated by functional abnormalities, specifically velopharyngeal incompetence (VPI), secondary to abnormal palatal muscular insertion. This study aims to characterize our experience using the Furlow Z-palatoplasty for the treatment of VPI in patients with submucous clefts. METHODS: A retrospective chart review was conducted looking at 24 patients diagnosed with symptomatic submucous clefts between 2000 and 2007 at Children's Hospital of New Orleans. Demographics such as age, gender, diagnosis, need for surgical correction, type of operation, complications, presence of genetic syndromes, need for secondary surgery, and need for myringotomy tubes were examined. RESULTS: The average age at initial surgery for the entire study population was 6.2 years. The success rate of our Furlow procedure was 66.7%, with 33.3% requiring secondary pharyngeal flaps. The genetic syndromic patient population had an average age at initial surgery of four years and experienced a lower primary success rate of 50%. The non-syndromic patient population had an average age at initial surgery of 7.3 years, with an 85.7% primary success rate. CONCLUSIONS: Our data supports the notion that Furlow Z-palatoplasty is an effective procedure in the treatment of submucous cleft palate with VPI, frequently without the need for secondary surgical procedures in the majority of patients, particularly those patients without syndromes.

Localization of the dominant deep inferior epigastric artery perforator by computed tomography angiogram: does the standard deep inferior epigastric artery perforator flap design include the dominant perforator?

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) free flap is the optimal autogenous reconstructive technique in many patients undergoing postmastectomy. Our aim was to evaluate the standard DIEP free flap design in relation to the dominant perforating vessels using computed tomography angiography (CTA). METHODS: We retrospectively reviewed CTAs from 75 patients who had undergone perforator flap reconstruction within the past year. Locations of the largest perforator with a minimum diameter of 2.0 mm piercing the anterior rectus fascia were recorded. RESULTS: Of 150 hemiabdomens reviewed, 146 (97.3%) had a dominant perforator. The median location for the dominant perforator was 3.3 cm lateral and 0.9 cm below the umbilicus. One hundred twenty-one (83%) of the dominant perforators arose within 3 cm of the umbilicus. One hundred one (69%) arose at or below the level of the umbilicus. Forty-five (31%) arose above the level of the umbilicus. Thirteen (9%) arose more than 2 cm above the umbilicus. CONCLUSIONS: The standard DIEP flap design incorporates most of the dominant perforating vessels. However, a significant number of perforators arise at or above the umbilicus, which would be near the edge or out of the standard design of the DIEP. Our findings support the use of preoperative CTA in the evaluation of patients undergoing DIEP free flap reconstruction. Modification of flap design to include the dominant perforating vessels should be considered when the dominant vessel is outside the standard design of the DIEP.

Virtual surgical planning in complex composite maxillofacial reconstruction.

BACKGROUND: Complex osteocutaneous maxillofacial reconstruction requiring multiple free flaps and with an extensive zone of injury can be fraught with complications and difficulty. Often, the remnants of native mandible are malpositioned and the skeletal structure of the upper face is distorted. The authors seek to extend the use of virtual planning to complex maxillofacial reconstruction by presenting their early experience in these difficult patients. METHODS: A retrospective chart review of 10 consecutive patients who underwent complex maxillofacial reconstruction using virtual surgical planning was undertaken. The authors define complex maxillofacial reconstruction as that requiring an osteocutaneous flap in which multiple osteotomies were required in addition to at least one of the following: need for multiple free flaps, history of osteoradionecrosis, and ballistic injury. Synthes Proplan CMF surgical planning was performed using computed tomographic scanning of the maxillofacial area and the donor site. Jigs and cutting guides were created and plates were prebent. The flap was harvested and osteotomized using the jigs and inset. Postoperative computed tomographic scanning was performed to evaluate the reconstruction. RESULTS: Ten consecutive patients who met the criteria underwent review. There were no intraoperative complications. Postoperative computed tomographic scans showed excellent contour of the osseous flaps. All patients had functional mandibular range of motion. CONCLUSIONS: Use of virtual surgical planning allows for complex maxillofacial reconstruction with multiple simultaneous free flaps to be performed reliably and successfully. The use of prefabricated jigs and precontoured plates eases osteocutaneous flap molding and inset, allowing for a more complex procedure to be successful.

Prospective dual role of mesenchymal stem cells in breast tumor microenvironment.

Breast cancer tissue is a heterogeneous cellular milieu comprising cancer and host cells. The interaction between breast malignant and non-malignant cells takes place in breast tumor microenvironment (TM), and has a crucial role in breast cancer progression. In addition to cellular component of TM, it mainly consists of cytokines released by tumor cells. The tumor-tropic capacity of mesenchymal stem cells (MSCs) and their interaction with breast TM is an active area of investigation. In the present communication, the interplay between the breast resident adipose tissue-derived MSCs (B-ASCs) and breast TM was studied. It was found that a distinct subset of B-ASCs display a strong affinity for conditioned media (CM) from two breast cancer cell lines, MDA-MB 231 (MDA-CM) and MCF-7 (MCF-CM). The expressions of several cytokines including angiogenin, GM-CSF, IL-6, GRO-α and IL-8 in MDA-CM and MCF-CM have been identified. Upon functional analysis a crucial role for GRO-α and IL-8 in B-ASCs migration was detected. The B-ASC migration was found to be via negative regulation of RECK and enhanced expression of MMPs. Furthermore, transcriptome analysis showed that migratory subpopulation express both pro- and anti-tumorigenic genes and microRNAs (miRNA). Importantly, we observed that the migratory cells exhibit similar gene and miRNA attributes as those seen in B-ASCs of breast cancer patients. These findings are novel and suggest that in breast cancer, B-ASCs migrate to the proximity of tumor foci. Characterization of the molecular mechanisms involved in the interplay between B-ASCs and breast TM will help in understanding the probable role of B-ASCs in breast cancer development, and could pave way for anticancer therapies.

Aging alters tissue resident mesenchymal stem cell properties.

Tissue resident mesenchymal stem cells (MSCs) are known to participate in tissue regeneration that follows cell turnover, apoptosis, or necrosis. It has been long known that aging impedes an organism's repair/regeneration capabilities. In order to study the age associated changes, the molecular characteristics of adipose tissue derived MSCs (ASCs) from three age groups of healthy volunteers, i.e., young, middle aged, and aged were investigated. The number and multilineage differentiation potential of ASCs declined with age. Aging reduces the proliferative capacity along with increases in cellular senescence. A significant increase in quiescence of G2 and S phase was observed in ASCs from aged donors. The expression of genes related to senescence such as CHEK1 and cyclin-dependent kinase inhibitor p16(ink4a) was increased with age, however genes of apoptosis were downregulated. Further, an age-dependent abnormality in the expression of DNA break repair genes was observed. Global microRNA analysis revealed an abnormal expression of mir-27b, mir-106a, mir-199a, and let-7. In ubiquitously distributed adipose tissue (and ASCs), aging brings about important alterations, which might be critical for tissue regeneration and homeostasis. Our findings therefore provide a better understanding of the mechanism(s) involved in stem cell aging and regenerative potential, and this in turn may affect tissue repair that declines with aging.

Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection.

BACKGROUND: Tissue resident mesenchymal stem cells (MSCs) are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. The ability of single cell clones isolated from adipose tissue resident MSCs (ASCs) to differentiate into cells of hematopoietic lineage has been previously demonstrated. In the present study, we investigated if the hematopoietic differentiated (HD) cells derived from ASCs could productively be infected with HIV-1. RESULTS: HD cells were generated by differentiating clonally expanded cultures of adherent subsets of ASCs (CD90+, CD105+, CD45-, and CD34-). Transcriptome analysis revealed that HD cells acquire a number of elements that increase their susceptibility for HIV-1 infection, including HIV-1 receptor/co-receptor and other key cellular cofactors. HIV-1 infected HD cells (HD-HIV) showed elevated p24 protein and gag and tat gene expression, implying a high and productive infection. HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC. HIV-1 restricting factors like APOBEC3F and TRIM5 also showed up regulation. HIV-1 infection increased apoptosis and cell cycle regulatory genes in HD cells. Although undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10. CONCLUSIONS: Considering the presence of profuse amounts of ASCs in different tissues, these findings suggest the possible role that could be played by HD cells derived from ASCs in HIV-1 infection. The undifferentiated ASCs were non-permissive to HIV-1 infection; however, HIV-1 exposure increased the expression of some hematopoietic lineage related genes. The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.

Persistent high glucose concentrations alter the regenerative potential of mesenchymal stem cells.

Type 2 diabetes is associated with numerous long-term complications. This study aims to investigate whether impaired function of tissue-resident multipotent cells play role in pathogenesis of allied complications. Adipose-tissue-derived mesenchymal stem cells (ASCs) derived from nondiabetic (nASCs) and diabetic (dASCs) donors were compared with regard to glucose metabolism, cell replication, apoptosis, and differentiation potential. The data evidenced that elevation of glucose reduces proliferative capacity of both dASCs and nASCs, but impacts dASCs more significantly. Incorporation of insulin enhanced cell replication especially in nASCs. dASCs show higher levels of cellular senescence and apoptosis than nASCs. Unlike nASCs, apoptosis is induced via intrinsic pathway in dASCs. Data also evidenced that high glucose concentrations cause prominent disparities in nASCs and dASCs in expression of genes involved in insulin resistance such as adiponectin and resistin. Some changes in gene expression were irreversible in dASCs when treated with insulin. Additionally, high glucose concentrations reduce osteogenic and chondrogenic potential of ASCs, but enhance adipogenic potential. These results indicate that in addition to involvement in insulin resistance, impaired function of mesenchymal stem cells that reside in adipose tissue as one of the major sources of adult stem cells might be responsible for complications related to diabetes type 2.

Microvascular free tissue transfer in organ transplantation patients: is it safe?

BACKGROUND: Traditionally, organ transplantation has been synonymous with patients with poor prognosis and outcome. Surgeons felt that the risks posed by immunosuppressive drugs outweighed the benefits of non-life-threatening procedures. With the enormous advances in the field of organ transplantation, a growing number of transplant patients present for a variety of surgical procedures. The objective of this report was to study the surgical outcome of organ transplantation patients who required reconstructive surgery using free tissue transfer. METHODS: A multicenter retrospective study was conducted on organ transplant patients who underwent elective microvascular free flap procedures. Patient chart review included cause of organ failure, medications, reconstruction site, flap choice, days hospitalized, complications, and outcome. RESULTS: Five independent medical centers participated in the study. Nineteen organ transplant patients required free flaps. Free flaps were used to reconstruct a variety of surgical defects, including breast, head and neck, and upper and lower extremities. There were no flap losses. Flaps used included musculocutaneous (n = 13), fasciocutaneous (n = 5), and osteocutaneous (n = 1) free flaps. Hospital length of stay ranged from 3 to 17 days. Complications included loss of skin graft, suture line dehiscence, and hematoma formation. Delayed wound healing was observed in two patients. CONCLUSIONS: In the properly selected patient, microvascular free tissue transfer can be performed safely and with acceptable surgical outcome. Contrary to popular belief, delayed wound healing from immunosuppressive agents was uncommon. Free tissue transfer in healthy organ transplant patients can be considered in reconstructive surgery decision making.

A 10-year retrospective review of 758 DIEP flaps for breast reconstruction.

This study examined 758 deep inferior epigastric perforator flaps for breast reconstruction, with respect to risk factors and associated complications. Risk factors that demonstrated significant association with any breast or abdominal complication included smoking (p = 0.0000), postreconstruction radiotherapy (p = 0.0000), and hypertension (p = 0.0370). Ninety-eight flaps (12.9 percent) developed fat necrosis. Associated risk factors were smoking (p = 0.0226) and postreconstruction radiotherapy (p = 0.0000). Interestingly, as the number of perforators increased, so did the incidence of fat necrosis. There were only 19 cases (2.5 percent) of partial flap loss and four cases (0.5 percent) of total flap loss. Patients with 45 flaps (5.9 percent) were returned to the operating room before the second-stage procedure. Patients with 29 flaps (3.8 percent) were returned to the operating room because of venous congestion. Venous congestion and any complication were observed to be statistically unrelated to the number of venous anastomoses. Overall, postoperative abdominal hernia or bulge occurred after only five reconstructions (0.7 percent). Complication rates in this large series were comparable to those in retrospective reviews of pedicle and free transverse rectus abdominis musculocutaneous flaps. Previous studies of the free transverse rectus abdominis musculocutaneous flap described breast complication rates ranging from 8 to 13 percent and abdominal complication rates ranging from 0 to 82 percent. It was noted that, with experience in microsurgical techniques and perforator selection, the deep inferior epigastric perforator flap offers distinct advantages to patients, in terms of decreased donor-site morbidity and shorter recovery periods. Mastery of this flap provides reconstructive surgeons with more extensive options for the treatment of postmastectomy patients.

Cheek and inferior eyelid reconstruction after skin cancer ablation.

Most patients with actinic lesions and skin cancer are skin type I or II, older than 50 years of age, and have a history of extensive sunlight exposure. These patients have been treated in our units according to universal principles. A multidisciplinary team approach can produce encouraging long-term results. The size and depth of the lesion are assessed in planning the ablation. The residual defect after the tumor resection is anticipated in the preoperative plan. Adequate resection is mandatory, even if the reconstruction must be delayed to ensure clear margins. Attention to unit and subunit anatomy facilitates adequate reconstruction with acceptable deformity. Placing scars in borders or along the lines of minimal skin tension reduces deformity. Planning the flap so that the donor site is in tissue areas with maximum laxity guards against donor site deformity. Flaps must be planned to avoid excess tension on the lower lid and central face. Attempts should be made to reduce scarring in the central face as seen in the frontal view. Respecting these principles will allow for reconstruction of the largest facial unit in a manner acceptable to the patient.