Increasing Diversity in Academic Medicine Via a Strategic Intermural Housestaff Leadership Development Program.

PROBLEM: By 2055, the United States will no longer have a single race or ethnic majority. As the nation's demographics change, the field of medicine must also change to meet the needs of diverse patients. APPROACH: In 2013, UT Southwestern Medical Center implemented the Housestaff Emerging Academy of Leaders (HEAL) program, which provides leadership development skills and training to underrepresented in medicine physician residents in preparation for academic medicine careers. Program leaders hypothesized that by providing housestaff with structured mentorship, career coaching, and individualized development plans, HEAL would increase interest in pursuing academic careers and prepare residents for faculty positions. HEAL has since expanded to graduate medical education programs nationwide. OUTCOMES: From 2013 to 2018, HEAL included housestaff at UT Southwestern and other Texas medical centers, totaling 392 enrollees. In 2019, the program increased to include housestaff from around the country. The first HEAL USA program had 39 housestaff, which increased to 173 in 2019, including 60 faculty from 31 U.S. academic medical centers. The 2019 HEAL USA preassessment survey (32 trainee responses) revealed that 10 (31%) of the housestaff were "extremely interested" in academic medicine, but only 1 (3%) felt "extremely confident" to pursue an academic medicine career. Postassessment responses to these same items (5 trainee responses) were 3 (60%) and 1 (20%), respectively, with 3 (60%) also feeling "extremely prepared" (1 [20%]) or "very prepared" (2 [40%]) to pursue an academic medicine career. Of 70 evaluable participants who attended at least 2 sessions and have graduated from residency, 47 (67%) have attained academic faculty positions, whereas 23 (33%) have pursued positions at nonacademic centers. NEXT STEPS: The next steps for HEAL USA will be continued expansion to additional medical centers and effective delivery of career development and leadership training to encourage participants to pursue academic medical careers.

Patient Satisfaction with and Use of Telemental Health Services in the Perinatal Period: a Survey Study.

We aimed to assess patients' utilization of and satisfaction with telemental health (TMH) in the perinatal period. We hypothesized that satisfaction with TMH would be at least equal to, if not greater than, with in-person appointments. We conducted a cross-sectional survey between March 2018-June 2019 to evaluate patient satisfaction with and use of TMH services in the perinatal period. Participants used TMH services across the second and third trimester of pregnancy and the first year post-partum. Nearly half of the patients (8/19, 42%) used TMH to see their provider within the first two weeks post-partum. Participants were most commonly in treatment for anxiety (14/19, 74%) and/or depression (9/19, 47%). Most participants agreed or strongly agreed (13/19, 69%) that TMH improved their access to healthcare and that they could see the clinician as well as if they met in person (14/19, 74%). TMH was a highly accepted and appreciated method of mental health care delivery for perinatal women when offered as an alternative to in-person or telephone sessions.

Mentoring Black Men in Medicine.

In recent years, there have been multiple publications about the dearth of Black men in medicine. Appreciating the fact that underrepresented minority physicians disproportionately care for America's underserved communities, the lack of diversity in health care is particularly disturbing. Of imminent concern is the critical shortage of Black men doctors. In this Perspective, the authors contend that while mentoring is often considered among the most important strategies to increase the number of Black men in medicine, unique challenges in this demographic can diminish its effectiveness. Among these challenges are below average primary school educational experiences and a general mistrust of society on the part of Black men, as well as difficulties overcoming stereotypes and social biases that others hold against them. Furthermore, acknowledging that mentorship is paramount in achieving success in the medical field, the authors provide a framework to assist mentors in recognizing and addressing situations and obstacles that may disrupt the mentoring relationship and hinder its potential to best serve Black men pursuing advancement in medicine. This framework is represented by the acronym RACE: Reluctance to discuss race, Access to mentors, Cultural mistrust and racial concordance, and Empathy.

Evolution in Monitoring of Free Flap Autologous Breast Reconstruction after Nipple-Sparing Mastectomy: Is There a Best Way?

BACKGROUND: Free flap monitoring in autologous reconstruction after nipple-sparing mastectomy remains controversial. The authors therefore examined outcomes in nipple-sparing mastectomy with buried free flap reconstruction versus free flap reconstruction incorporating a monitoring skin paddle. METHODS: Autologous free flap reconstructions with nipple-sparing mastectomy performed from 2006 to 2015 were identified. Demographics and operative results were analyzed and compared between buried flaps and those with a skin paddle for monitoring. RESULTS: Two hundred twenty-one free flaps for nipple-sparing mastectomy reconstruction were identified: 50 buried flaps and 171 flaps incorporating a skin paddle. The most common flaps used were deep inferior epigastric perforator (64 percent), profunda artery perforator (12.1 percent), and muscle-sparing transverse rectus abdominis myocutaneous flaps (10.4 percent). Patients undergoing autologous reconstructions with a skin paddle had a significantly greater body mass index (p = 0.006). Mastectomy weight (p = 0.017) and flap weight (p < 0.0001) were significantly greater in flaps incorporating a skin paddle. Comparing outcomes, there were no significant differences in flap failure (2.0 percent versus 2.3 percent; p = 1.000) or percentage of flaps requiring return to the operating room (6.0 percent versus 4.7 percent; p = 0.715) between groups. Buried flaps had an absolute greater mean number of revision procedures per nipple-sparing mastectomy (0.82) compared with the skin paddle group (0.44); however, rates of revision procedures per nipple-sparing mastectomy were statistically equivalent between the groups (p = 0.296). CONCLUSION: Although buried free flap reconstruction in nipple-sparing mastectomy has been shown to be safe and effective, the authors' technique has evolved to favor incorporating a skin paddle, which allows for clinical monitoring and can be removed at the time of secondary revision. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Breast Tissue Expanders with Magnetic Ports: Clinical Experience at 1.5 T.

BACKGROUND: The purpose of this study was to evaluate breast tissue expanders with magnetic ports for safety in patients undergoing abdominal/pelvic magnetic resonance angiography before autologous breast reconstruction. METHODS: Magnetic resonance angiography of the abdomen and pelvis at 1.5 T was performed in 71 patients in prone position with tissue expanders with magnetic ports labeled "MR Unsafe" from July of 2012 to May of 2014. Patients were monitored during magnetic resonance angiography for tissue expander-related symptoms, and the chest wall tissue adjacent to the tissue expander was examined for injury at the time of tissue expander removal for breast reconstruction. Retrospective review of these patients' clinical records was performed. T2-weighted fast spin echo, steady-state free precession and gadolinium-enhanced spoiled gradient echo sequences were assessed for image artifacts. RESULTS: No patient had tissue expander or magnetic port migration during the magnetic resonance examination and none reported pain during scanning. On tissue expander removal (71 patients, 112 implants), the surgeons reported no evidence of tissue damage, and there were no operative complications at those sites of breast reconstruction. CONCLUSION: Magnetic resonance angiography of the abdomen and pelvis in patients with certain breast tissue expanders containing magnetic ports can be performed safely at 1.5 T for pre-autologous flap breast reconstruction perforator vessel mapping. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Profunda Artery Perforator Flap Experience for Breast Reconstruction.

BACKGROUND: The profunda artery perforator flap was first introduced for breast reconstruction in 2010. In this article, the authors analyze the results of all profunda artery perforator flaps performed by their group to date. METHODS: A retrospective review was completed of consecutive profunda artery perforator flaps performed by the senior author (R.J.A.) from 2010 to 2014. Patient demographics, indications, operative techniques, flap specifics, complications, and number of operations were recorded. RESULTS: Ninety-six patients have undergone 164 profunda artery perforator flap operations for breast reconstruction since 2010. Reconstructions were performed following breast cancer management (59.5 percent), following prophylactic mastectomy for cancer risk reduction (35.7 percent), and for congenital breast deformity (4.8 percent). The average age of the patients was 48 years (range, 24 to 64 years) and their average body mass index was 22.5 kg/m. Average flap weight was 367.4 g and average pedicle length was found to be 10.2 cm. The success rate of the profunda artery perforator flap was greater than 99 percent, with a 3 percent take-back rate and only one flap loss recorded. Complications included hematoma (1.9 percent), seroma (6 percent), fat necrosis (7 percent), and donor-site infection (1.9 percent). CONCLUSIONS: The profunda artery perforator flap is an excellent option for breast reconstruction. Advantages include a reliable blood supply, long pedicle, thick donor tissue, and a favorable donor site. Currently, the profunda artery perforator flap is second only to the deep inferior epigastric artery perforator among flaps used by the authors for breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

To Resect or Not to Resect: The Effects of Rib-Sparing Harvest of the Internal Mammary Vessels in Microsurgical Breast Reconstruction.

BACKGROUND: The internal mammary vessels are the most commonly used recipients for microsurgical breast reconstructions. Often, the costal cartilage is sacrificed to obtain improved vessel exposure. In an effort to reduce adverse effects associated with traditional rib sacrifice, recent studies have described less-invasive, rib-sparing strategies. METHODS: After obtaining institutional review board's approval, a retrospective review of all patients undergoing microsurgical breast reconstruction at a single institution between November 2007 and December 2013 was conducted. Patients were divided into two cohorts for comparison: rib-sacrificing and rib-sparing internal mammary vessel harvests. RESULTS: A total of 547 reconstructions (344 patients) met inclusion criteria for this study. A total of 64.9% (n = 355) underwent rib-sacrificing internal mammary vessel harvest. Cohorts were similar in baseline patient characteristics, indications for surgery, and cancer therapies. However, patients undergoing rib-sparing reconstructions had significantly shorter operative times (440 vs. 476 minutes; p < 0.01), and significantly less postoperative pain on postoperative day (POD) 1 (2.8/10 vs. 3.4/10; p = 0.033) and POD2 (2.4/10 vs. 3.0/10; p = 0.037). Furthermore, patients undergoing rib-sparing techniques had greater incidence of fat necrosis requiring excision (12.5 vs. 2.8%; p < 0.01) and a trend toward higher incidence of hematoma, venous thrombosis, and arterial thrombosis when compared with rib-sacrificing patients. CONCLUSIONS: Rib-sparing harvest of internal mammary vessels is a feasible technique in microsurgical breast reconstruction. However, given the significant increase in fat necrosis requiring surgical excision, the trend toward increased postoperative complications, and no significant difference in postoperative revision rates, the purported benefits of this technique may fail to outweigh the possible risks.

Stromal Indian hedgehog signaling is required for intestinal adenoma formation in mice.

BACKGROUND & AIMS: Indian hedgehog (IHH) is an epithelial-derived signal in the intestinal stroma, inducing factors that restrict epithelial proliferation and suppress activation of the immune system. In addition to these rapid effects of IHH signaling, IHH is required to maintain a stromal phenotype in which myofibroblasts and smooth muscle cells predominate. We investigated the role of IHH signaling during development of intestinal neoplasia in mice. METHODS: Glioma-associated oncogene (Gli1)-CreERT2 and Patched (Ptch)-lacZ reporter mice were crossed with Apc(Min) mice to generate Gli1CreERT2-Rosa26-ZSGreen-Apc(Min) and Ptch-lacZ-Apc(Min) mice, which were used to identify hedgehog-responsive cells. Cyp1a1Cre-Apc (Apc(HET)) mice, which develop adenomas after administration of ß-naphthoflavone, were crossed with mice with conditional disruption of Ihh in the small intestine epithelium. Apc(Min) mice were crossed with mice in which sonic hedgehog (SHH) was overexpressed specifically in the intestinal epithelium. Intestinal tissues were collected and analyzed histologically and by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction. We also analyzed levels of IHH messenger RNA and expression of IHH gene targets in intestinal tissues from patients with familial adenomatous polyposis (n = 18) or sessile serrated adenomas (n = 15) and normal colonic tissue from control patients (n = 12). RESULTS: Expression of IHH messenger RNA and its targets were increased in intestinal adenomas from patients and mice compared with control colon tissues. In mice, IHH signaling was exclusively paracrine, from the epithelium to the stroma. Loss of IHH from Apc(HET) mice almost completely blocked adenoma development, and overexpression of SHH increased the number and size of adenomas that developed. Loss of IHH from Apc(HET) mice changed the composition of the adenoma stroma; cells that expressed α-smooth muscle actin or desmin were lost, along with expression of cyclooxygenase-2, and the number of vimentin-positive cells increased. CONCLUSIONS: Apc mutant epithelial cells secrete IHH to maintain an intestinal stromal phenotype that is required for adenoma development in mice.

Autologous breast reconstruction: preoperative magnetic resonance angiography for perforator flap vessel mapping.

BACKGROUND: Selection of a vascular pedicle for autologous breast reconstruction is time consuming and depends on visual evaluation during the surgery. Preoperative imaging of donor site for mapping the perforator artery anatomy greatly improves the efficiency of perforator selection and significantly reduces the operative time. In this article, we present our experience with magnetic resonance angiography (MRA) for perforator vessel mapping including MRA technique and interpretation. METHODS: We have performed over 400 MRA examinations from August 2008 to August 2013 at our institution for preoperative imaging of donor site for mapping the perforator vessel anatomy. Using our optimized imaging protocol with blood pool magnetic resonance imaging contrast agents, multiple donor sites can be imaged in a single MRA examination. Following imaging using the postprocessing and reporting tool, we estimated incidence of commonly used perforators for autologous breast reconstruction. RESULTS: In our practice, anterior abdominal wall tissue is the most commonly used donor site for perforator flap breast reconstruction and deep inferior epigastric artery perforators are the most commonly used vascular pedicle. A thigh flap, based on the profunda femoral artery perforator has become the second most used flap at our institution. In addition, MRA imaging also showed evidence of metastatic disease in 4% of our patient subset. CONCLUSION: Our MRA technique allows the surgeons to confidently assess multiple donor sites for the best perforator and flap design. In conclusion, a well-performed MRA with specific postprocessing provides an accurate method for mapping perforator vessel, at the same time avoiding ionizing radiation.

Microsurgical breast reconstruction in thin patients: the impact of low body mass indices.

BACKGROUND: The purpose of this investigation was to examine patients with low body mass index (BMI) regarding the feasibility to perform autologous breast reconstruction in such patients, as well as to determine optimal donor sites and evaluate outcomes accordingly. PATIENTS AND METHODS: All patients undergoing microsurgical breast reconstruction were divided into three cohorts based on BMI. Group 1 included patients with BMI greater than or equal to 22 kg/m(2) and was defined "low-normal BMI." Patients with BMI 22 to 25 kg/m(2) were placed in Group 2, labeled as "high-normal BMI." Group 3, defined as "overweight," included patients with BMI greater than 25 kg/m(2), but less than 30 kg/m(2). Patients were then analyzed based on demographics, breast cancer history, intraoperative details, complications, and revisionary surgeries. F-tests, chi-square goodness-of-fit tests, and Freeman-Halton extension of the Fisher exact tests were used for statistical analysis. RESULTS: During the study period, a total of 259 reconstructions were performed. Group 1 included 30 patients (n = 49 flaps), Group 2 included 58 patients (n = 98 flaps), and Group 3 included 69 patients (n = 112 flaps). Patients undergoing nipple-areolar sparing mastectomy were more likely to be in Groups 1 (39% [n = 19]) and 2 (37% [n = 37]) as compared with Group 3 (14.2% [n = 16]) (p < 0.001) as compared with the overweight cohort. Patients with increasing BMI were more likely to undergo abdominally based free flaps as compared with alternative donor sites (Group 1 = 2.26, Group 2 = 7.9, Group 3 = 27 [p < 0.001]). CONCLUSIONS: Abdominally based free flaps are possible in the majority of patients, however alternative harvest sites have to be used more frequently in low BMI patients.

Induction of ectopic taste buds by SHH reveals the competency and plasticity of adult lingual epithelium.

Taste buds are assemblies of elongated epithelial cells, which are innervated by gustatory nerves that transmit taste information to the brain stem. Taste cells are continuously renewed throughout life via proliferation of epithelial progenitors, but the molecular regulation of this process remains unknown. During embryogenesis, sonic hedgehog (SHH) negatively regulates taste bud patterning, such that inhibition of SHH causes the formation of more and larger taste bud primordia, including in regions of the tongue normally devoid of taste buds. Here, using a Cre-lox system to drive constitutive expression of SHH, we identify the effects of SHH on the lingual epithelium of adult mice. We show that misexpression of SHH transforms lingual epithelial cell fate, such that daughter cells of lingual epithelial progenitors form cell type-replete, onion-shaped taste buds, rather than non-taste, pseudostratified epithelium. These SHH-induced ectopic taste buds are found in regions of the adult tongue previously thought incapable of generating taste organs. The ectopic buds are composed of all taste cell types, including support cells and detectors of sweet, bitter, umami, salt and sour, and recapitulate the molecular differentiation process of endogenous taste buds. In contrast to the well-established nerve dependence of endogenous taste buds, however, ectopic taste buds form independently of both gustatory and somatosensory innervation. As innervation is required for SHH expression by endogenous taste buds, our data suggest that SHH can replace the need for innervation to drive the entire program of taste bud differentiation.

In vitro assessment of MRI issues at 3-Tesla for a breast tissue expander with a remote port.

OBJECTIVES: A patient with a breast tissue expander may require a diagnostic assessment using magnetic resonance imaging (MRI). To ensure patient safety, this type of implant must undergo in vitro MRI testing using proper techniques. Therefore, this investigation evaluated MRI issues (i.e., magnetic field interactions, heating, and artifacts) at 3-Tesla for a breast tissue expander with a remote port. METHODS: A breast tissue expander with a remote port (Integra Breast Tissue Expander, Model 3612-06 with Standard Remote Port, PMT Corporation, Chanhassen, MN) underwent evaluation for magnetic field interactions (translational attraction and torque), MRI-related heating, and artifacts using standardized techniques. Heating was evaluated by placing the implant in a gelled-saline-filled phantom and MRI was performed using a transmit/receive RF body coil at an MR system reported, whole body averaged specific absorption rate of 2.9-W/kg. Artifacts were characterized using T1-weighted and GRE pulse sequences. RESULTS: Magnetic field interactions were not substantial and, thus, will not pose a hazard to a patient in a 3-Tesla or less MRI environment. The highest temperature rise was 1.7°C, which is physiologically inconsequential. Artifacts were large in relation to the remote port and metal connector of the implant but will only present problems if the MR imaging area of interest is where these components are located. CONCLUSIONS: A patient with this breast tissue expander with a remote port may safely undergo MRI at 3-Tesla or less under the conditions used for this investigation. These findings are the first reported at 3-Tesla for a tissue expander.

Venous coupler size in autologous breast reconstruction--does it matter?

BACKGROUND: Autologous microvascular breast reconstruction is an increasingly common procedure. While arterial anastomoses are traditionally being hand-sewn, venous anastomoses are often completed with a coupler device. The largest coupler size possible should be used, as determined by the smaller of either the donor or recipient vein. While its efficacy has been shown using 3.0-mm size and greater couplers, little is known about the consequences of using coupler sizes less than or equal to 2.5 mm. METHODS: A retrospective chart review of patients undergoing autologous breast reconstruction was conducted at NYU Medical Center between November 2007 and November 2011. Flaps were divided into cohorts based on coupler size used: 2.0 mm, 2.5 mm, and 3.0 mm. Outcomes included incidence of arterial or venous insufficiency, hematoma, fat necrosis, partial flap loss, full flap loss, and need for future fat grafting. RESULTS: One-hundred ninety-seven patients underwent 392 flaps during the study period. Patients were similar in age, type of flap, smoking status, and radiation history. Coupler size less than or equal to 2.0 mm was found to be a significant risk factor for venous insufficiency (P = 0.038), as well as for development of fat necrosis (P = 0.041) and future need for fat grafting (P = 0.050). In multivariate analysis, body mass index was found to be an independent risk factor for skin flap necrosis (P = 0.010) and full flap loss (P = 0.035). CONCLUSIONS: Complications were significantly increased in patients where couplers of 2.0 mm or less were used, therefore to be avoided whenever possible. When needed, more aggressive vessel exposure through rib harvest, the use of thoracodorsal vessels or hand-sewing the anastomosis should be considered in cases of internal mammary vein caliber of 2.0 mm or less. CLINICAL QUESTION: Therapeutic. LEVEL OF EVIDENCE: Level III.

Stacked profunda artery perforator flaps for unilateral breast reconstruction: a case report.

A patient with a severe case of Poland syndrome presented with a painful capsular contracture from a previous implant-based breast reconstruction. She desired the implant to be removed and to proceed with autologous reconstruction, sizeable enough to match the volume of her contralateral breast. A paucity of abdominal donor tissue combined with the patient's hesitancy to acquire an anterior scar excluded this location as a free tissue transfer option. As an alternative donor site, the profunda artery perforator (PAP) flap was chosen. Bilateral PAP flaps were harvested and stacked using anterograde and retrograde anastomoses to the internal mammary vessels. Enough volume was present to fill her chest wall concavity and provide adequate projection to achieve symmetry with her contralateral breast. Her donor sites healed well and remained inconspicuous, without generating difficulties sitting. In conclusion, stacked PAP flaps provide an excellent alternative to an abdominal donor site for achieving large volume unilateral breast reconstruction.

The role of autologous fat grafting in secondary microsurgical breast reconstruction.

BACKGROUND: Autologous breast reconstruction offers higher rates of patient satisfaction, but not all patients are ideal candidates, often due to inadequate volume of donor sites. Although autologous fat grafting is frequently used to augment volume and contour abnormalities in implant-based breast reconstruction, its clear utility in microsurgical breast reconstruction has yet to be defined. Here, we examined patients undergoing autologous microsurgical breast reconstruction with and without the adjunct of autologous fat grafting to clearly define utility and indications for use. METHODS: A retrospective review of all patients undergoing autologous breast reconstruction with microvascular free flaps at a single institution between November 2007 and October 2011 was conducted. Patients were divided into 2 groups as follows: those requiring postoperative fat grafting and those not requiring fat grafting. Patient demographics, indications for surgery, history of radiation therapy, patient body mass index, mastectomy specimen weight, need for rib resection, flap weight, and complications were analyzed in comparison. RESULTS: Two hundred twenty-eight patients underwent 374 microvascular free flaps for breast reconstruction. One hundred (26.7%) reconstructed breasts underwent postoperative fat grafting, with an average of 1.12 operative sessions. Fat was most commonly injected in the medial and superior medial poles of the breast and the average volume injected was 147.8 mL per breast (22-564 mL). The average ratio of fat injected to initial flap weight was 0.59 (0.07-1.39). Patients undergoing fat grafting were more likely to have had deep inferior epigastric perforator and profunda artery perforator flaps as compared to muscle-sparing transverse rectus abdominis myocutaneous. Patients additionally were more likely to have a prophylactic indication 58% (n = 58) versus 42% (n = 117) (P = 0.0087), rib resection 68% (n = 68) versus 54% (n = 148) (P < 0.0153), and acute postoperative complications requiring operative intervention 7% (n = 7) versus 2.1% (n = 8) (P < 0.0480). Additionally, patients undergoing autologous fat grafting had smaller body mass index, mastectomy weight, and flap weight. CONCLUSIONS: Fat grafting is most commonly used in those breasts with rib harvest, deep inferior epigastric perforator flap reconstructions, and those with acute postoperative complications. It should be considered a powerful adjunct to improve aesthetic outcomes in volume-deficient autologous breast reconstructions and additionally optimize contour in volume-adequate breast reconstructions.

Microsurgical breast reconstruction for nipple-sparing mastectomy.

BACKGROUND: Nipple-sparing mastectomy warrants thorough preoperative evaluation to effectively achieve risk reduction, high patient satisfaction, and improved aesthetic outcome. To the authors' knowledge, this review represents the largest series of microsurgical breast reconstructions following nipple-sparing mastectomies. METHODS: All patients undergoing nipple-sparing mastectomy with microsurgical immediate breast reconstruction treated at New York University Medical Center (2007-2011) were identified. Patient demographics, breast cancer history, intraoperative details, complications, and revision operations were examined. Descriptive statistical analysis, including t test or regression analysis, was performed. RESULTS: In 51 patients, 85 free flap breast reconstructions (n = 85) were performed. The majority of flaps were performed for prophylactic indications [n = 55 (64.7 percent)], mostly through vertical incisions [n = 40 (47.0 percent)]. Donor sites included abdominally based [n = 66 (77.6 percent)], profunda artery perforator [n = 12 (14.1 percent)], transverse upper gracilis [n = 6 (7.0 percent)], and superior gluteal artery perforator [n = 1 (1.2 percent)] flaps. The most common complications were mastectomy skin flap necrosis [n = 11 (12.7 percent)] and nipple necrosis [n = 11 (12.7 percent)]. There was no correlation between mastectomy skin flap or nipple necrosis and choice of incision, mastectomy specimen weight, body mass index, or age (p > 0.05). However, smoking history was associated with nipple necrosis (p < 0.01). CONCLUSIONS: This series represents a high-volume experience with nipple-sparing mastectomy followed by immediate microsurgical reconstruction. When appropriately executed, it can deliver low complication rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Nipple-sparing mastectomy and immediate free-flap reconstruction in the large ptotic breast.

Because of increased risk for nipple necrosis, many surgeons believe large ptotic breasts to be a relative contraindication to nipple-sparing mastectomy (NSM). A retrospective review was performed on 85 consecutive patients who underwent NSM with 141 immediate perforator free-flap breast reconstructions. We analyzed the subset of patients with large ptotic breasts, defined as cup size C or greater, sternal notch to nipple distance greater than 24 cm and grade 2 or 3 breast ptosis. Of the 85 patients, 19 fit the inclusion criteria. Breast cup size ranged from 34C to 38DDD. There was 1 case of nipple necrosis in the patient with previous breast radiation (5%), 1 hematoma (5%), and no flap losses. Five (26%) patients underwent subsequent mastopexy or breast reduction, a mean of 6.6 months after the primary procedure. We demonstrate that NSM and free-flap breast reconstruction can be safely and reliably performed in selected patients.

Breast reconstruction with the profunda artery perforator flap.

BACKGROUND: The use of perforator flaps has allowed for the transfer of large amounts of soft tissue with decreased morbidity. For breast reconstruction, the deep inferior epigastric perforator flap, the superior and inferior gluteal artery perforator flaps, and the transverse upper gracilis flap are all options. The authors present an alternative source using posterior thigh soft tissue based on profunda artery perforators, termed the profunda artery perforator flap. METHODS: Preoperative imaging helps identify posterior thigh perforators from the profunda femoris artery. These are marked, and an elliptical skin paddle, approximately 27 × 7 cm, is designed 1 cm inferior to the gluteal crease. Dissection proceeds in a suprafascial plane until nearing the perforator, at which point subfascial dissection is performed. The flap has a long pedicle (approximately 7 to 13 cm), which allows more options when performing anastomosis at the recipient site. The long elliptical shape of the flap allows coning of the tissue to form a more natural breast shape. RESULTS: All profunda artery perforator flaps have been successful. The donor site is well tolerated and scars have been hidden within the gluteal crease. Long-term follow-up is needed to evaluate for possible fat necrosis of the transferred tissue. CONCLUSIONS: The authors present a new technique for breast reconstruction with a series of 27 flaps. This is an excellent option when the abdomen is not available because of the long pedicle, muscle preservation, ability to cone the tissue, and hidden scar. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor.

In many organ systems such as the skin, gastrointestinal tract and hematopoietic system, homeostasis is dependent on the continuous generation of differentiated progeny from stem cells. The rodent incisor, unlike human teeth, grows throughout the life of the animal and provides a prime example of an organ that rapidly deteriorates if newly differentiated cells cease to form from adult stem cells. Hedgehog (Hh) signaling has been proposed to regulate self-renewal, survival, proliferation and/or differentiation of stem cells in several systems, but to date there is little evidence supporting a role for Hh signaling in adult stem cells. We used in vivo genetic lineage tracing to identify Hh-responsive stem cells in the mouse incisor and we show that sonic hedgehog (SHH), which is produced by the differentiating progeny of the stem cells, signals to several regions of the incisor. Using a hedgehog pathway inhibitor (HPI), we demonstrate that Hh signaling is not required for stem cell survival but is essential for the generation of ameloblasts, one of the major differentiated cell types in the tooth, from the stem cells. These results therefore reveal the existence of a positive-feedback loop in which differentiating progeny produce the signal that in turn allows them to be generated from stem cells.

Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma.

The Hedgehog (Hh) signaling pathway is inappropriately activated in certain human cancers, including medulloblastoma, an aggressive brain tumor. GDC-0449, a drug that inhibits Hh signaling by targeting the serpentine receptor Smoothened (SMO), has produced promising anti-tumor responses in early clinical studies of cancers driven by mutations in this pathway. To evaluate the mechanism of resistance in a medulloblastoma patient who had relapsed after an initial response to GDC-0449, we determined the mutational status of Hh signaling genes in the tumor after disease progression. We identified an amino acid substitution at a conserved aspartic acid residue of SMO that had no effect on Hh signaling but disrupted the ability of GDC-0449 to bind SMO and suppress this pathway. A mutation altering the same amino acid also arose in a GDC-0449-resistant mouse model of medulloblastoma. These findings show that acquired mutations in a serpentine receptor with features of a G protein-coupled receptor can serve as a mechanism of drug resistance in human cancer.