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Background: Lymphedema (LE) is a significant clinical problem for breast cancer survivors. While the water displacement test and circumferential assessment using a tape measure (TM) are common methods to assess differences in arm volumes, faster and more reliable methods are needed. Study purposes, in breast cancer survivors (n = 294), were to compare the average total arm volumes and interlimb volume ratios for women with and without a history of LE, using a TM and three-dimensional (3D), whole-body surface scanner (3D scan); compare the level of agreement between arm volumes and interlimb volume ratios obtained using the two devices; and evaluate the percent agreement between the two measures in classifying cases of LE using three accepted thresholds. Methods and Results: Measurements were done using a spring-loaded TM and Fit3D ProScanner. Paired t-tests and Bland-Altman analyses were used to achieve the study aims. For circumference and volume comparisons, compared with the 3D scan, values obtained using the TM were consistently smaller. In terms of level of agreement, the Bland-Altman analyses demonstrated large biases and wide limits of agreement for the calculated arm volumes and volume ratios. In terms of the classification of caseness, using the 200-mL interlimb volume difference criterion resulted in 81.6% overall agreement; using the >10% volume difference between the affected and unaffected arms resulted in 78.5% overall agreement; and using the volume ratio ≥1.04 criterion resulted in 62.5% overall agreement. For all three accepted threshold criteria, the percentage of cases was significantly different between the TM and 3D scan techniques. Conclusions: The 3D technology evaluated in this study has the potential to be used for self-initiated surveillance for LE. With improvements in landmark identification and software modifications, it is possible that accurate and reliable total arm volumes can be calculated and used for early detection.

BACKGROUND Complications following vascular procedures involving the groin can lead to significant morbidity. Achieving stable soft tissue coverage over sites of revascularization can help mitigate complications. Prior evidence supports the use of muscle flaps in reoperative groins and in high risk patient populations to reduce postoperative complications. Data regarding the use of prophylactic muscle flap coverage of the groin is lacking. Therefore, the purpose of this study is to evaluate the effect of immediate prophylactic muscle flap coverage of vascular wounds involving the groin. METHODS A retrospective cohort study was performed on all patients undergoing primary open vascular procedures involving the groin for occlusive, aneurysmal, or oncologic disease between 2014 and 2020 at a single institution where plastic surgery was involved in closure. Patient demographics, comorbidities, surgical details, and postoperative complications were compared between patients who had sartorius muscle flap coverage of the vascular repair versus layered closure alone. RESULTS A total of 133 consecutive groins were included in our analysis. A sartorius flap was used in 115 groins (86.5%) and a layered closure was used in 18 (13.5%). Wound breakdown was similar between groups (25.2% sartorius vs. 38.9% layered closure, P = 0.26). However, the rate of reoperation was significantly higher in the layered closure group (50.0% vs. 12.2%, P < 0.01). Among patients who experienced wound breakdown (N = 36), a larger proportion of layered closure patients required operative intervention (71.4% vs. 20.7%, P = 0.02). Other rates of complications were not statistically different between groups. CONCLUSIONS In patients undergoing primary open vascular procedures involving the groin, patients who underwent prophylactic sartorius muscle flap closure had lower rates of reoperation. Although incisional breakdown was similar between the groups overall, the presence of a vascularized muscle flap overlying the vascular repair was associated with reduced need for reoperation and allowed more wounds to be managed with local wound care alone. Consideration should be given to this low morbidity local muscle flap in patients undergoing vascular procedures involving the groin.

We present a comparative series to utilize minimally invasive endoscopic, total extraperitoneal laparoscopic (TEP-lap), and transabdominal preperitoneal robotic perforator (TAP-RAP) harvest of the deep inferior epigastric (DIE) vessels for autologous breast reconstruction (ABR) to mitigate donor site morbidity. We hypothesized that TEP-lap and TAP-RAP harvests of abdominal-based free flaps are safe techniques associated with decreased fascial incision when compared with the endoscopic harvest.We designed a retrospective cohort series of subjects with newly diagnosed breast cancer who presented for ABR using endoscopic (control), laparoscopic, or robotic assistance between September 2017 and April 2019. The primary outcome variables were flap success (i.e., absence of perioperative flap loss), fascial incision length, and intraoperative complications. Secondary variables included operating time, costs, and postoperative complications within 90 days (arterial thrombosis, venous congestion, bulge/hernia, and operative revision). Exclusion criteria included90 days follow-up.In total 94, 38, and 3 subjects underwent endoscopic, TEP-lap, and TAP-RAP flap harvests. Mean lengths of fascial incisions for the endoscopic and laparoscopic cohorts were 4.5 ± 0.5 cm and 2.0 ± 0.6 cm (p 0.0001), while incision length depended on the concurrent procedure in the robotic cohort. No subjects required conversion to an open harvest. There were no bleeding complications, intra-abdominal injuries, flap losses, or abdominal bulges/hernias noted in the TEP-lap and TAP-RAP cohorts.Minimally invasive DIEP flap harvest may decrease fascial injury when compared with conventional open harvest. There are significant trade-offs among harvest methods. TEP-lap harvest may better balance the trade-off related to abdominal wall morbidity.

Background Gender-affirming surgery is a medically necessary treatment to alleviate gender dysphoria for transgender patients. Although previous studies suggest improved psychosocial outcomes after gender-affirming surgery, there are no transgender-specific instruments available to assess its effects on patient quality of life. Methods Using qualitative methods, the authors developed the first quality-of-life survey, the University of California, San Francisco, Gender Quality of Life (UCSF Gender QoL) survey, for trans male patients undergoing gender-affirming mastectomy. The UCSF Gender QoL survey was then administered prospectively to 51 trans male patients undergoing inframammary mastectomy with free nipple grafting at the University of California, San Francisco. The brief version of the World Health Organization Quality of Life survey was also given as a measure of external validity. The Cronbach alpha was value calculated to measure internal validity. Results Thirty-six patients completed surveys 6 weeks after surgery, and 22 patients completed surveys 1 year after surgery, for response rates of 71 percent and 43 percent, respectively. The UCSF Gender QoL survey detected a significant improvement in quality of life 6 weeks and 1 year after chest surgery. The effect sizes were large, and the Cronbach alpha exhibited excellent internal validity. Conclusions This study establishes the UCSF Gender QoL survey as one of the first patient-reported outcomes tools for evaluating quality of life in trans male patients after gender-affirming chest reconstruction. Although the study is limited by a small cohort at a single center, establishing the validity of the UCSF Gender QoL survey provides an invaluable tool for future research into various aspects of gender-affirming chest surgery.

Background: Oncoplastic reduction mammoplasty is an accepted method of breast conserving surgery that also allows for potentially improved symmetry and aesthetics compared to other techniques and allows for larger tissue volumes to be removed with acceptable cosmetic outcomes. Neoadjuvant systemic chemotherapy (NAC) is increasingly used for the treatment of patients with breast cancer. While there is some data that oncoplastic reduction may delay timing of adjuvant radiation, we sought to examine this in our patients, and specifically to compare complications and time to radiation in patients who received NAC to those that didn’t. Methods: A retrospective analysis was done of all patients with DCIS or invasive cancer who underwent a reduction mammoplasty and received adjuvant radiation at our single institution from 2009-2018. Patients who received NAC were compared to those that did not. Results: A total of 114 patients underwent reduction mammoplasty as part of their oncologic surgery and received adjuvant radiation at our institution. Of those, 40.4% received neoadjuvant chemotherapy and 49.1% received no neoadjuvant treatment. A total of 38 patients (33.3%) had some postoperative complication with 8.8% having a serious complication that required intervention. Adjuvant radiation started after 8 weeks in 74.6% of patients and after 12 weeks in 38.6% of patients, with the majority of these delays due to non-clinical factors. A total of 29.4% of patients had a delay due to wound healing issues. There was no association between NAC and delayed radiation due to wound healing (p=0.18). Discussion: Oncoplastic reduction mammoplasty is a safe option for breast-conserving surgery in patients who have received NAC. The receipt of NAC in itself does not delay timing of adjuvant radiation or lead to increases in delayed wound healing. We are additionally examining other factors and their possible interaction with NAC, including diabetes, smoking, BMI and breast reduction size. In those with larger tumors receiving NAC who would otherwise not be candidates for breast conserving surgery, oncoplastic reduction should be considered as an appropriate option for surgical management. Reduction also allows for wider excision which may mitigate the impact of the longer time from surgery to radiation. Citation Format: Kelly Hewitt, Susan Wu, Laura Barnes, Joanna Yang, Merisa Piper. Reduction mammoplasty in the setting of neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-37.

Background In the last decade, a number of studies have demonstrated the utility of indocyanine green (ICG) angiography in predicting mastectomy skin flap necrosis for immediate breast reconstruction. However, data are limited to investigate this technique for autologous breast reconstruction. Although it may have the potential to improve free flap outcomes, there has not been a large multicenter study to date that specifically addresses this application. Methods A thorough literature review based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines was conducted. All studies that examined the use of intraoperative ICG angiography or SPY to assess perfusion of abdominally based free flaps for breast reconstruction from January 1, 2000, to January 1, 2020, were included. Free flap postoperative complications including total flap loss, partial flap loss, and fat necrosis were extracted from selected studies. Results Nine relevant articles were identified, which included 355 patients and 824 free flaps. A total of 472 free flaps underwent clinical assessment of perfusion intraoperatively, whereas 352 free flaps were assessed with ICG angiography. Follow-up was from 3 months to 1 year. The use of ICG angiography was associated with a statistically significant decrease in flap fat necrosis in the follow-up period (odds ratio = 0.31, P = 0.02). There was no statistically significant difference for total or partial flap loss. Conclusions From this systematic review, it can be concluded that ICG angiography may be an effective and efficient way to reduce fat necrosis in free flap breast reconstruction and may be a more sensitive predictor of flap perfusion than clinical assessment alone. Future prospective studies are required to further determine whether ICG angiography may be superior to clinical assessment in predicting free flap outcomes.

Although rates of total skin-sparing (nipple-sparing) mastectomies are increasing, the oncologic safety of this procedure has not been evaluated in invasive lobular carcinoma (ILC). ILC is the second most common type of breast cancer, and its diffuse growth pattern and high positive margin rates potentially increase the risk of poor outcomes from less extensive surgical resection. We compared time to local recurrence and positive margin rates in a cohort of 300 patients with ILC undergoing either total skin-sparing mastectomy (TSSM), skin-sparing mastectomy, or simple mastectomy between the years 2000–2020. Data were obtained from a prospectively maintained institutional database and were analyzed by using univariate statistics, the log-rank test, and multivariate Cox proportional hazards models. Of 300 cases, mastectomy type was TSSM in 119 (39.7%), skin-sparing mastectomy in 52 (17.3%), and simple mastectomy in 129 (43%). The rate of TSSM increased significantly with time (p

Background As our population ages, the demand for total knee arthroplasty (TKA) will dramatically increase to ensure an independent lifestyle with unimpeded and pain-free ambulation. Complications will be inevitable, especially in that patient with preexisting soft tissue deficits or extensive scarring in the knee region. Under these circumstances, prophylactic soft tissue augmentation should be strongly considered and be extremely beneficial. Methods A retrospective review of all TKA procedures at our institutions over the past two decades revealed seven patients who specifically had soft tissue augmentation prior to their definitive TKA. Each had a single perforator flap used to achieve this. In no cases was a muscle flap used for this purpose. Excluded were all patients who had a flap of any kind for coverage of an exposed prosthesis or to accomplish wound healing after the TKA. Results Seven perforator flaps were utilized in seven patients for soft tissue replacement prior to the ultimate TKA. For smaller defects in three patients, a local island medial sural artery perforator flap was used. For larger defects in four patients, an anterolateral thigh perforator free flap was necessary. All flaps were successful. The only complication was an implant infection after one anterolateral thigh free flap that required a revision arthroplasty that eventually allowed salvage. Unrestricted ambulation was possible in all patients except for one who had a preexisting contralateral below-knee amputation. Conclusion As the number of TKA procedures in the near future increases, prevention of the absolute number of complications becomes even more important. An awareness that any knee region suboptimal soft tissue base can lead to wound breakdown and then periprosthetic infection should alert all involved that prevention of this sequela can be best achieved by prior soft tissue augmentation. Preferably, this may be possible by capturing the assets of local and free perforator flaps.

Background. Immediate tissue expander placement in postmastectomy breast reconstruction can be complicated by seroma or infection, requiring further imaging studies or interventions. This study compares dual-port tissue expanders, with both an aspiration and expansion port, with single-port expanders in terms of postoperative complications and further interventions. Methods:. Patients with immediate tissue expander placement from March 2019 to March 2020 were reviewed. Complications included seroma, infection, hematoma, necrosis, and malposition of the expander. Further intervention included aspiration, ultrasound imaging, interventional radiology (IR) drainage, or return to operating room. Results:. In total, 128 dual-port expanders were compared with 125 single-port expanders. Patients with single-port expanders were younger (P = 0.022) and of lower BMI (P = 0.01). There were no significant differences in key complications between these groups. In multivariate analysis, single-port expanders had a 3.4× higher odds of postoperative ultrasound imaging when controlling for texture, placement, and age (P = 0.01). Mean time to IR drain placement in the dual-port group was approximately 30 days after placement in single port (51.1 versus 21.4 days, P = 0.013). Thirty-four percent of dual-port expanders had at least one aspiration in clinic performed by plastic surgery, versus 2% of single port that required ultrasound-guided aspiration (P < 0.001). Conclusions:. There were no differences in key postoperative complications between the two expander cohorts. Dual-port expanders significantly reduced postoperative ultrasound imaging, and delayed IR drain placement. The added convenience of clinic aspirations likely reduced costs related to utilization of resources from other departments.

Background: Invasive lobular carcinoma of the breast (ILC) has higher rates of false negative imaging than invasive ductal carcinoma, and lower rates of neoadjuvant therapy (NAT) use. We evaluated the accuracy of Breast Imaging Reporting And Data System (BIRADS) findings on magnetic resonance imaging (MRI) after either neoadjuvant chemotherapy or endocrine therapy, and determined whether imaging change correlates with disease free survival. Methods: We queried a database of 674 ILC cases treated at UCSF from 1981-2017 and identified all patients treated with NAT. We reviewed MRI reports and recorded BIRADS descriptors of findings, maximal tumor diameter for mass or non-mass enhancement (NME), and subjective radiologist comments on progression or improvement. We used the t-test, chi-squared test, Pearson's correlation, and Kaplan Meier survival estimates to evaluate the accuracy of MRI after NAT compared to true tumor size on pathology, and the relationship between imaging change and disease free interval in Stata 14.2. Results: Of 136 patients with ILC treated with NAT, we included 101 women who had a post-treatment breast MRI report available. Of these, 58.4% received neoadjuvant chemotherapy, and 41.6% neoadjuvant endocrine therapy. After NAT, MRI findings were mass only in 43%, both mass/NME in 33%, NME only in 18%, and neither in 5%. Maximal diameter of mass on post-treatment MRI underestimated true size by a mean of 3.3 cm (range -3.6 to 15.3 cm). NME size on post-treatment MRI underestimated true size by a mean of 1.87 cm (range -7.2 to 9.7 cm). Mass size on MRI underestimated true size by ≥1 cm in 61.5% of cases; this size discrepancy was associated with increased positive margins (46.4% versus 20%, p=0.011). NME size on MRI underestimated true size by at ≥1 cm in 65.6%. The correlation coefficient between mass size on MRI and true size was 0.34 (p=0.0041), which increased to 0.67 (p Table 1.Patient and tumor characteristics. Neoadjuvant chemotherapy (n=59)Neoadjuvant endocrine therapy (n=42)P valueMean age (yrs, 95% CI)53.6 (50.9-56.3)61.3 (58.4-64.1)0.0002Subtype 0.105ER+ PR+ HER2-29 (53.7%)23 (62.16%) ER+ PR- HER2-14 (25.9%)13 (35.14%) ER- PR- HER2-1 (1.85%)0 HER2+10 (18.5%)1 (2.7%) Grade 0.076114 (25%)16 (38.1%) 237 (66.1%)26 (61.9%) 35 (8.93%)0 Surgical stage Conclusions: Maximal tumor diameter on MRI after NAT in ILC vastly underestimates true tumor size. While these findings suggest using caution when using an MRI for surgical planning in patients with ILC, particularly if there is associated NME, the trend towards improved disease free survival in those with a subjective improvement is intriguing and suggests that MRI changes could become an early predictor of outcomes. Citation Format: Fahrner-Scott KE, Wong JM, Piper M, Ewing C, Alvarado M, Esserman LJ, Hylton N, Mukhtar RA. Accuracy of MRI after neoadjuvant therapy for invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-15-15.

Background Prepectoral breast reconstruction following mastectomy has become a more widely performed technique in recent years because of its numerous benefits for women. These include full pectoralis muscle preservation, reduced loss of strength, reduced pain, and elimination of animation deformity. As with any breast reconstruction technique, widespread adoption is dependent on a low morbidity profile in the setting of postmastectomy radiation therapy, as this adjuvant therapy is routine in breast cancer treatment. The authors assess the clinical outcomes of patients undergoing postmastectomy radiation therapy following prepectoral breast reconstruction, and compare these to outcomes of patients undergoing postmastectomy radiation therapy with submuscular reconstruction. Methods A single surgeon's experience with immediate prepectoral breast reconstruction, followed by postmastectomy radiation therapy, from 2015 to 2017 was reviewed. Patient demographics and incidence of complications during the tissue expander stage were assessed. In addition, the morbidity profile of these patients was compared to that of patients undergoing submuscular/dual-plane reconstruction and postmastectomy radiation therapy over the same period. Results Over 3 years, 175 breasts underwent immediate prepectoral reconstruction, and 236 breasts underwent immediate submuscular/dual-plane reconstruction. Overall rates of adjuvant radiation therapy (postmastectomy radiation therapy) were similar between prepectoral [26 breasts (14.9 percent)] and submuscular [31 breasts (13.1 percent)] (p = 0.6180) reconstruction. There were no significant differences in complication rates between the two reconstructive cohorts, in the setting of postmastectomy radiation therapy, including rates of explantation (15.4 percent versus 19.3 percent; p = 0.695). Conclusions Prepectoral breast reconstruction is a safe and effective option in the setting of postmastectomy radiation therapy. The morbidity profile is similar to that encountered with submuscular reconstruction in this setting. Clinical question/level of evidence Therapeutic, III.

Background Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described. Methods We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS). Results In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p = 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p = 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy. Conclusions Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.

Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons' knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer.

Invasive lobular carcinoma (ILC) of the breast grows in a diffuse pattern, making complete surgical excision difficult. This results in high rates of positive margins and low rates of successful breast-conserving surgery. We hypothesized that utilizing oncoplastic surgical techniques and selective shave margins would be associated with lower positive margin rates and increased breast conservation in women with ILC. We performed a retrospective cross-sectional analysis in a large cohort of prospectively collected ILC cases who received surgical treatment at the University of California, San Francisco, between 1992 and 2017. We identified all patients with histologically proven, unilateral or bilateral, stage 1–3 ILC. The primary outcome was positive margin rates, defined as no ink on tumor. We identified 365 tumors in 358 women, with an average age of 61 years, who underwent breast-conserving surgery, and found that the use of oncoplastic techniques (odds ratio [OR] 0.4, 95% confidence interval [CI] 0.21–0.79, p = 0.008) and the selective use of shave margins (OR 0.393, 95% CI 0.22–0.7, p = 0.002) were significantly associated with lower positive margin rates, when adjusted for tumor size and multifocality. The success rate for breast-conservation surgery was 75%, with a 25% conversion rate to mastectomy. Surgeons should consider routine use of oncoplastic techniques and shave margins when performing breast-conservation surgery for women with ILC as these methods are associated with significantly lower odds of having positive margins and higher breast-conservation rates.

Background: Invasive lobular carcinoma (ILC) of the breast differs from invasive ductal carcinoma in its non-cohesive growth pattern. These diffuse tumors pose challenges for accurate size assessment as well as surgical resection. Patients with ILC have higher rates of positive margins and lower rates of successful breast conservation surgery. Oncoplastic surgical techniques such as oncoplastic reduction mammoplasty and lumpectomy with oncoplastic closure can allow for removal of larger areas of breast tissue than lumpectomy alone. Whether or not these techniques improve the success of breast conservation in patients with ILC is unknown. Methods: We queried a prospectively maintained surgical database and identified 384 women treated for ILC at UCSF between 1992 and April 2017. We reviewed pathology and operative reports, and clinical outcomes data, and identified 199 women who had an initial attempt at breast conservation. Data were analyzed in Stata 14.2. Results: Average age was 61 years (range 39-84), and 69% of patients underwent lumpectomy, 16% had lumpectomy with oncoplastic closure, and 15% had oncoplastic reduction mammoplasty. The majority of tumors were hormone receptor positive, Her2 negative, grade 2, T1 or T2, and 28% were node positive. A total of 156 women (78%) had successful breast conservation; of these, 34% had one re-excision, and 1 patient had two re-excisions. Positive margins were seen in 40% of patients overall, and were significantly lower in the lumpectomy with oncoplastic closure group and those who had shave margins taken. Among the patients who underwent lumpectomy only, obtaining shave margins was significantly associated with final negative margins (71% versus 53%, p = 0.033). Patients with oncoplastic reduction mammoplasty had significantly larger average tumor size (4.1 cm), and significantly more tissue removed (167 cm3). LumpectomyLumpectomy with oncoplastic closureOncoplastic reduction mammoplastyP valueTumor size (mean)2.4 cm2.1 cm4.1 cm Conclusions: Tailoring the surgical treatment to tumor size can increase the rate of successful breast conservation surgery for these diffuse, often non-palpable lobular cancers. For the women with the largest tumors, oncoplastic reduction mammoplasty was often recommended. This group likely represents women who were borderline candidates for breast conservation; despite this, oncoplastic reduction mammoplasty allowed 77% to ultimately have successful breast conservation. For the women with smaller tumors, removing additional tissue with shave margins and using oncoplastic techniques for closure when necessary clearly reduced positive margin rates. Surgeons should routinely obtain shave margins when performing partial mastectomy for women with ILC. Citation Format: Wong JM, Piper ML, Ewing C, Alvarado M, Esserman LJ, Sbitany H, Foster RD, Mukhtar RA. The use of oncoplastic surgical techniques to increase successful breast conservation in invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-16.

Background:Nipple-sparing mastectomy with immediate prosthetic reconstruction is routinely performed because of excellent aesthetic results and safe oncologic outcomes. Typically, subpectoral expanders are placed, but in select patients, this can lead to significant postoperative pain and animation

Introduction Plantar melanoma tumors are traditionally treated with wide local excision based on depth of invasion, followed by delayed reconstruction once negative surgical margins are confirmed. However, delayed reconstruction requires care for an open wound, a prolonged treatment course, and the need for an additional surgery. Immediate reconstruction has been shown to be oncologically safe in head and neck melanoma, but little is described in the literature regarding immediate reconstruction in plantar melanoma. We present our experience with immediate reconstruction after wide local excision for lower extremity plantar melanomas. Methods We performed a retrospective review of all patients with biopsy-proven plantar melanoma who underwent wide local excision followed by immediate reconstruction of any type between 1999 and 2014 at the University of California, San Francisco. Patient demographics, postoperative complications, reoperation rates, and oncologic outcomes were collected. Results Thirty-eight patients were identified, with a mean follow-up of 34 months. Skin grafts were the most common method of reconstruction, followed by primary closure, local flaps, and free flaps. Only 1 patient had a major complication, which was skin graft loss requiring reoperation. Eight patients had either local or distant recurrence (21%). Discussion Immediate reconstruction for plantar melanomas can be safely performed with recurrence rates comparable and in line with previously published studies of wide local excision for plantar melanoma. This technique has the potential to achieve oncologically safe outcomes with less overall morbidity.

The concern about cancer recurrence has traditionally resulted in delaying kidney transplantation for 2-5 years after a cancer diagnosis in patients who are otherwise eligible for transplant. This period of inactive status to observe the tumor biology can result in significant morbidity and decreased quality of life for patients with end-stage renal disease (ESRD). We reported the novel application of genomic profiling assays in breast cancer to identify low-risk cancers in two patients with ESRD who were able to have the mandatory inactive status eliminated prior to kidney transplantation.

Approximately 50,000 women in the United States undergo mastectomy and immediate prosthetic breast reconstruction annually, and most receive postoperative prophylactic antibiotics. The effect of these antibiotics on the risk of surgical-site infections remains unclear.The authors searched the Medline, Embase, and Cochrane Library databases for studies that compared less than 24 hours and greater than 24 hours of antibiotics following immediate prosthetic breast reconstruction. Primary outcomes were surgical-site infections and implant loss. Conservative random effects models were used to obtain pooled relative risk estimates.The authors identified 927 studies, but only four cohort studies and one randomized controlled trial met their inclusion criteria. Unadjusted incidences of surgical-site infections were 14 percent with more than 24 hours of antibiotics, 19 percent with less than 24 hours of antibiotics, and 16 percent overall. Unadjusted incidences of implant loss were 8 percent with more than 24 hours of antibiotics, 10 percent with less than 24 hours of antibiotics, and 9 percent overall. The pooled relative risk of implant loss was 1.17 (95 percent CI, 0.39 to 3.6) with less than 24 hours of antibiotics, which was not statistically significant.Prolonged antibiotic use did not have a statistically significant effect on reducing surgical-site infections or implant loss. There was significant heterogeneity between studies, and prolonged antibiotics may have increased the risk of implant loss in the randomized controlled trial. Definitive evidence may only be obtained with data from more prospective randomized controlled trials.

INTRODUCTION The combined approach using both an implant and autologous tissue for breast reconstruction has become more common over the last 10 years. We sought to provide a systematic review and outcomes analysis of this technique. METHODS We searched PubMed and the Cochrane Library database to identify studies that described implant augmentation of autologous flaps for breast reconstruction. The references of selected articles were also reviewed to identify any additional pertinent articles. RESULTS We identified 11 articles, which included 230 patients and 378 flaps. Implants used ranged in size from 90 to 510 cc, with an average size of 198 cc. Implants were more frequently placed at the time of autologous reconstruction and in the subpectoral plane. There were no total flap losses, and partial flap loss occurred in 3 patients (1%). There were no cases of venous or arterial thrombosis and no early return to the operating room for flap compromise. Eight implants (2%) were lost because of infection or extrusion, and capsular contracture occurred in 9 breasts (3%). When stratified by the timing of implant placement (immediate vs delayed), there were no significant differences in any postoperative outcomes except the immediate group had a higher infection rate. CONCLUSIONS The criteria for women to be candidates for autologous tissue breast reconstruction can be expanded by adding an implant underneath the flap. We found the overall flap loss rate is comparable with standard autologous flap reconstruction, and the implant loss rate is lower than that in patients who undergo prosthetic reconstruction alone.

Rates of positive margins after surgical resection of invasive lobular carcinoma (ILC) are high (ranging from 18 to 60%), yet the efficacy of re-excision lumpReceptor subtypeectomy for clearing positive margins is unknown. Concerns about the diffuse nature of ILC may drive increased rates of completion mastectomy to treat positive margins, thus lowering breast conservation rates. We therefore determined the success rate of re-excision lumpectomy in women with ILC and positive margins after surgical resection. We identified 314 cases of stage I-III ILC treated with breast conserving surgery (BCS) at the University of California, San Francisco. Surgical procedures, pathology reports, and outcomes were analyzed using univariate and multivariate statistics and Cox-proportional hazards models. We evaluated outcomes before and after the year 2014, when new margin management consensus guidelines were published. Positive initial margins occurred in 118 (37.6%) cases. Of these, 62 (52.5%) underwent re-excision lumpectomy, which cleared the margin in 74.2%. On multivariate analysis, node negativity was significantly associated with successful re-excision (odds ratio [OR] 3.99, 95% CI 1.15–13.81, p = 0.029). After 2014, we saw fewer initial positive margins (42.7% versus 25.5%, p = 0.009), second surgeries (54.6% versus 20.2%, p p

Summary:. Anterolateral thigh (ALT) free flaps have become reliable options for head-to-toe reconstruction. Although perforator anatomy is fairly predictable, in cases of eccentric perforator location, we proposed shifting the entire flap laterally and preserving a medial bipedicled flap between the original incision and the new medial flap margin. This facilitates primary donor site closure instead of harvesting a flap larger than anticipated. We conducted a retrospective chart review of ALT flaps performed between 2007 and 2019 and identified patients who underwent bipedicled closure of the donor site. Demographics, flap characteristics, and surgical technique were evaluated. Six patients had bipedicled donor site closure related to primary perforators located lateral to the original flap design. The mean defect size was 91 cm2, and bipedicled flap width ranged from 4 to 6 cm. All donor sites were closed primarily. Five of the donor thigh sites healed without complications, and 1 patient had superficial delayed healing of the medial bipedicled incision, which healed with local wound care. The ALT has become an invaluable flap in microsurgical reconstruction, yet it is not without limitations. Primary donor site closure is generally not feasible for larger flaps, thus necessitating skin grafting of the donor site and/or prolonged wound care. Our technique facilitates primary closure of the donor site in patients who otherwise would have required harvest of a larger than necessary flap based on eccentric perforator anatomy. The medial bipedicled flap is straightforward, reproducible, and allows for modifications of the original flap design to better fit the defect.

Background Advances in medicine and surgery have allowed patients, who in the past would have required more aggressive amputations, to maintain longer stump lengths. Microvascular free tissue transfer has become increasingly popular to preserve limb length and optimize functionality. We present our experience using microvascular free flap reconstruction to preserve lower extremity limb length in the setting of high-energy trauma. Methods We conducted an Institutional Review Board-approved retrospective review of patients at three San Francisco hospitals who underwent free flap reconstruction after high-energy trauma between 2003 and 2015. We included all patients who underwent free flap reconstruction for lower extremity limb length preservation. We reviewed patient demographics, preoperative variables, intraoperative details, and postoperative outcomes, including complications, functional status, reoperation rates, and need for revision amputation. Results Twelve patients underwent microvascular free tissue transfer for limb length preservation. Overall, the patients had similar preoperative comorbidities and a mean age of 44. Six patients had postoperative complications: three minor complications and three major complications. Seven patients had additional surgeries to improve the contour of the flap. One patient required revision amputation, while the remaining 11 patients preserved their original limb length. The majority of patients were fully ambulatory, and four used a prosthesis. Conclusion Microvascular free tissue transfer can be used to effectively maintain lower extremity stump length following trauma. Although these patients often require multiple surgeries and face lengthy hospital courses, this technique enables preservation of a functional extremity that would otherwise require a more proximal amputation.

Background Deep inferior epigastric perforator (DIEP) flaps are routinely elevated on a single dominant perforator from the deep epigastric vascular system. However, the single perforator may not always perfuse an entire flap adequately, particularly suprascarpal tissue. We often perform “dual-plane” single perforator DIEP flaps by rerouting the superficial (SIEA/V) system directly into a branch of the deep (DIEA/V) vascular system pedicle, thus allowing both systems to contribute and enhance flap perfusion. Methods A prospectively collected database of patients undergoing microvascular breast reconstruction was reviewed for patients undergoing “dual-plane” DIEP flaps. These were matched to a similar cohort of patients undergoing “traditional” single perforator DIEP free flaps over the same time period. Treatment demographics and flap-specific morbidity outcomes were assessed, including performance in the setting of radiation. Results Over 2 years, 23 “dual-plane” DIEP flaps were performed (15 patients), compared with 35 single-perforator “traditional” DIEP flaps (23 patients). Rates of delayed healing were similar between both cohorts (2.9 vs. 4.3%, p = 0.28). Rates of palpable fat necrosis were significantly lower in “dual-plane” DIEP flaps compared with “traditional” flaps (0 vs. 14.3%, p = 0.03). Rates of clinically palpable fat necrosis following radiation were significantly lower in the “dual-plane” flaps (4.3 vs. 40%, p = 0.02). Conclusion The “dual-plane” DIEP flap is one we routinely consider in our algorithm, as it allows for full preservation of functional abdominal musculature, and offers enhanced flap perfusion by incorporating both the deep and superficial (dominant) vascular systems. This results in lower fat necrosis rates, particularly in the setting of post-reconstruction radiation.

Reconstruction of partial mastectomy defects with oncoplastic approaches has become increasingly popular as a strategy for improving aesthetic outcomes and extending the option of breast conservation therapy. However, interpretation of reported oncologic outcomes and postoperative complications has been challenging because of limited data and significant variability in surgical technique and degree of tissue rearrangement.Studies describing oncoplastic mammoplasty or partial mastectomy reconstruction were identified from the MEDLINE and Cochrane databases. Only studies reporting the use of oncoplastic reduction mammoplasty techniques with significant breast parenchymal rearrangement were included for analysis. Primary outcomes assessed were postoperative complications and oncologic outcomes, including local recurrence rates and need for re-excision or completion mastectomy.Seventeen articles met the inclusion criteria, representing 1324 oncoplastic cases. Reported follow-up ranged from 20 to 73 months. Of the 12 studies with at least 2 years' mean/median follow-up, the pooled local-regional recurrence rate was 3.1%. Fifteen articles reported re-excision and completion mastectomy rates (3.5% and 3.7%, respectively). Twelve articles reported postoperative complications. Overall, 4.6% of patients had wound dehiscence, 4.3% developed fat necrosis, 2.8% developed an infection, 0.9% had either partial or total nipple necrosis, and 0.6% had seromas.Partial mastectomy reconstruction with oncoplastic reduction techniques is associated with high rates of successful breast conservation and low rates of required re-excisions, likely due to the ability to take wide tumor margins without compromising aesthetic outcome. Future studies should consistently report complications, recurrences, and patient-reported outcomes to improve our ability to evaluate the use of this technique.

Axillary web syndrome (AWS) is a poorly understood but common cause of significant morbidity after axillary lymph node dissection for breast cancer. It is characterized by painful scar tissue formation and contracture extending from the axilla down the medial arm which limits shoulder and arm mobility. We sought to gain a better understanding of its pathophysiology and available treatments. Additionally, we present our preliminary experience with 2 novel treatment methods: (1) percutaneous needle cord disruption with fat grafting, (2) Xiaflex injection to the cording.In order to gain better understanding of current treatment modalities, we performed a literature search to identify articles that described axillary cording after axillary dissection exclusively for breast cancer. We performed operative percutaneous cord disruption and immediate autologous fat grafting in 18 patients. Xiaflex injection was performed in one patient. Details from the 2 new treatment modalities are described.Described treatments in the literature include physical therapy, nonsteroidal anti-inflammatories, moist heat, and 1 case of Ascueven Forte. Typically, symptoms lasted from 1 week to 2 years, and most cases resolved by 3 months postoperatively with return to preoperative functionality. We found our 2 new treatment modalities markedly improved arm and shoulder range of motion, overall daily functioning, and pain. Aesthetic outcomes were also improved with softening of the cords.Axillary web syndrome remains an incompletely understood postoperative phenomenon, which warrants further research. Those patients who develop severe cording often do not respond to traditional therapy and may require more aggressive treatment. Our 2 novel techniques provide alternative options for treating this condition.

The surgical management of breast cancer has changed dramatically over the past 30 years, attributed to improved chemotherapy regimens and a better understanding of tumor biology. There is now a greater emphasis on decreasing surgical morbidity and preserving the breast form. The evolution of oncoplastic surgery has enabled more patients to be candidates for breast-conserving therapy, and the preservation of the entire skin and nipple areolar complex with mastectomy has markedly improved esthetic and patient-reported outcomes. This review provides an overview of the reconstructive options for partial and complete mastectomy, as well as discusses several key factors which markedly influence outcomes.

Reconstruction of lumpectomy defects with reduction mammoplasty techniques can improve aesthetic outcomes and patient satisfaction. However, one concern with the substantial tissue rearrangement required is the possible difficulty with mammographic follow up and/or increased recommendations for future biopsies. We performed a retrospective review of 49 patients who underwent oncoplastic reduction mammoplasty between 2001 and 2009 who were age-matched to patients who underwent lumpectomy without reconstruction. Mammography reports at 6 months, 1, 2, and 5 years postoperatively were reviewed for predominant findings, Breast Imaging Reporting and Data System final assessments, and recommendations for biopsy. There was no significant difference in abnormal mammographic findings prompting biopsy between the two cohorts at 6 months, 2 years, and 5 years postoperatively (p > 0.05). Biopsy rates over the 5-year period did not differ significantly between the two cohorts [9 (18 %) lumpectomy cohort, 12 (24 %) oncoplastic cohort, p = 0.46]. Overall cancer-to-biopsy ratio was 33 % in the lumpectomy cohort and 42 % in the oncoplastic cohort (p = 1.00). Although substantial tissue rearrangement is performed at the time of oncoplastic reduction mammoplasty, our results reveal no increased incidence of postoperative mammographic abnormalities or unnecessary biopsies compared to lumpectomy alone. This demonstrates that fear of increasing mammographic abnormalities and biopsies after reduction mammoplasty is unfounded and should not prevent utilization of this technique if it can optimize cosmetic outcomes and extend the option of breast conservation.

Background Adipose fat transfer is increasingly used for contour corrections of the tumor bed after lumpectomy and breast reconstructions after mastectomy. The lipophilic nature of the fat tissue may render adipocytes an ideal vehicle with which to deliver a high boost of an antiestrogen to the tumor bed to serve as an adjunct systemic hormonal therapy. The authors therefore tested whether adipocytes could safely be loaded with an antiestrogen and allow for release at therapeutic concentrations to treat breast cancer. Methods Adipose tissue was collected from patients undergoing autologous fat grafting. The influence of adipose tissue on tumorigenesis was determined both in vitro and in vivo using breast cancer cell lines. Ex vivo, adipose tissue was assessed for its ability to depot fulvestrant and inhibit the growth of breast cancer cell lines. Results Adipose tissue harvested from patients did not promote breast cancer cell growth in vitro or in an in vivo mouse model. Adipose tissue was successfully loaded with fulvestrant and released at levels sufficient to inhibit estrogen receptor signaling and growth of breast cancer cells. Conclusions This work supports the hypothesis that adipose tissue used for autologous fat grafting can serve as a novel method for local drug delivery. As this technique is used to reconstruct a variety of postsurgical defects following cancer resection, this approach for local drug delivery may be an effective alternative in therapeutic settings beyond breast cancer.

Current guidelines in the United States require reporting only the 30-day postoperative outcomes to standardized databases, including the National Surgical Quality Improvement Program (NSQIP). Thus, many breast implant-related complications go unreported in standard databases. We sought to characterize late periprosthetic infections following implant-based breast reconstruction.We conducted a retrospective analysis of all women who underwent expander/implant reconstruction from 2005 to 2014 at two institutions. All periprosthetic infections were identified and divided into early and late cohorts (≤30 days or30 days). Infection was defined as any episode where antibiotics were initiated or a prosthetic device was explanted because of clinical evidence of the infection.In the 1820 patients (2980 breasts) identified, 421 periprosthetic infections occurred (14%). Of these, 173 (41%) were early and 248 (59%) were late (mean time to infection = 66.4 ± 101.9 days). Patients with late infections were more likely to be current smokers or have diabetes than patients with early infections (p 0.034 for both). Infections caused by gram-negative bacteria and antimicrobial-resistant strains of Staphylococcus were more common in the early infection group (p 0.001 for both). Implant loss due to infection was more common in the late infection group (p = 0.037).Late periprosthetic infections following implant-based breast reconstruction are underestimated in national outcome databases and have unique risk factors and microbiology compared to early infections. A system-level change in reevaluating and redefining a timeline for tracking and treating implant infections is necessary, given the substantial morbidity associated with, and frequency of, late periprosthetic infections.

Background: Complex hindfoot pathology may benefit from vascularized bone flap reconstruction rather than traditional bone grafting techniques. Medial femoral condyle (MFC) flaps provide vascularized periosteum, skin, and corticocancellous bone. Methods: A retrospective, single-institution cohort study of consecutive MFC flaps performed for complicated hindfoot reconstruction between 2013 and 2019 was reviewed. Radiologic follow-up assessed osseous union and clinical outcomes were evaluated with the American Orthopaedic Foot & Ankle Society (AOFAS) hindfoot score. Thirty MFC flaps were performed in 28 patients for complex hindfoot pathology. Twenty-seven flaps had adequate clinical and radiographic follow-up (mean 15.8 months). Results: The majority presented with avascular necrosis (83%) and failed prior operations (67%, mean 3.1). Most hindfoot procedures involved arthrodesis (n = 24, 80%); tibiotalocalcaneal (n = 11) and talonavicular (n = 7) most frequently. Mean osseous flap volume was 10.3 cm3 (range 1.7-18.4 cm3); one flap required takeback for venous congestion but no total flap losses occurred. Primary osseous union was initially achieved in 20 patients (74%, mean 217 days). Six flaps developed interface nonunion; 5 underwent revision arthrodesis and ultimately achieved union in 24/27 flaps (89%, mean 271 days). Risk factors for nonunion were body mass index (BMI) >30 ( P = .017) and prior arthrodesis ( P = .042). Mean AOFAS hindfoot scores increased significantly from 52.3 preoperatively to 70.7 postoperatively ( P < .001). Subscore analysis demonstrated significant improvement in postoperative pain scores from 14.2 to 27.3 out of 40 ( P < .001). Conclusion: The MFC free flap provided vascularized bone for complicated foot and ankle reconstruction with relatively low donor site morbidity, promising osseous union results, and improved functional outcomes. Level of Evidence: Level IV, retrospective case series.

Acquired thoracic dystrophy is a complication associated with early open repair of pectus excavatum resulting from extensive cartilage resection. The condition can cause serious functional and physiologic impairments, including cardiac compression and restrictive pulmonary function. We describe a 17-year-old boy with acquired thoracic dystrophy after Ravitch repair of pectus excavatum during infancy, whom we treated with distraction osteogenesis. The patient had a marked deformity of the chest wall and general hypoplasia of the central portion of the ribcage, with resultant symptomatic dyspnea on exertion and reduced pulmonary function. After osteotomies and distraction osteogenesis of bilateral ribs 4–8 using customized distraction devices, he had improved thoracic contour, resolution of dyspnea, and decreased restrictive pulmonary symptoms. This case suggests that distraction osteogenesis, already used extensively in craniomaxillofacial and orthopedic surgery, may be a novel method for management of this condition.

Hepatic steatosis is generally thought to develop via peripheral mechanisms associated with obesity. We show that chronic central infusion of leptin suppresses hepatic lipogenic gene expression and reduces triglyceride content via stimulation of hepatic sympathetic activity. This leptin function is independent of feeding and body weight but requires phosphatidylinositol 3-kinase (PI3K) signaling. Attenuation of leptin-induced PI3K signaling, brought about by transgenic expression of phosphatase and tensin homolog (PTEN) in leptin receptor neurons, leads to decreased hepatic sympathetic tone and increased triglyceride levels without affecting adiposity or hepatic insulin signaling. Central leptin’s effects on hepatic norepinephrine levels and triglyceride content are blunted in these mutant mice. Simultaneous downregulation of PI3K and signal transducer and activator of transcription-3 (Stat3) in leptin receptor neurons does not exacerbate obesity but causes more severe hepatic steatosis. Together, our results indicate that central cellular leptin resistance in PI3K signaling manifests as hepatic steatosis without causing obesity.

OBJECTIVE Hypothalamic leptin resistance is found in most common forms of obesity, such as diet-induced obesity, and is associated with increased expression of suppressor of cytokine signaling 3 (Socs3) in the hypothalamus of diet-induced obese animals. This study aims to determine the functional consequence of Socs3 upregulation on leptin signaling and obesity, and to investigate whether Socs3 upregulation affects energy balance in a cell type–specific way. RESEARCH DESIGN AND METHODS We generated transgenic mice overexpressing Socs3 in either proopiomelanocortin (POMC) or leptin receptor–expressing neurons, at levels similar to what is observed in diet-induced obesity. RESULTS Upregulation of Socs3 in POMC neurons leads to impairment of STAT3 and mammalian target of rapamycin (mTOR)–S6K-S6 signaling, with subsequent leptin resistance, obesity, and glucose intolerance. Unexpectedly, Socs3 upregulation in leptin receptor neurons results in increased expression of STAT3 protein in mutant hypothalami, but does not lead to obesity. CONCLUSIONS Our study establishes that Socs3 upregulation alone in POMC neurons is sufficient to cause leptin resistance and obesity. Socs3 upregulation impairs both STAT3 and mTOR signaling before the onset of obesity. The lack of obesity in mice with upregulated Socs3 in leptin receptor neurons suggests that Socs3's effect on energy balance could be cell type specific. Our study indicates that POMC neurons are important mediators of Socs3's effect on leptin resistance and obesity, but that other cell types or alteration of other signaling regulators could contribute to the development of obesity.

Summary Background In recent years, dramatic advances in the multidisciplinary treatment of pediatric sarcoma have resulted in significant improvement in the long-term survival of the patient. Thus, following tumor resection, significant effort has gone into limb salvage and improving functional outcomes. Plastic surgeons, in conjunction with orthopedic surgeons, are using techniques in microvascular free-tissue transfer and rotational flap surgery to preserve limb length. This study presents a review of the current reconstructive strategies and the oncologic, surgical, and functional outcomes in this population. Methods Using the Pubmed and Cochrane Library databases, studies describing lower extremity plastic surgical reconstruction were identified following pediatric lower extremity sarcoma resection. This study included those studies which described reconstructive techniques, oncologic and functional outcomes, and surgical complications. Results A total of nine articles were identified, yielding 96 pediatric patients. The most common procedures performed were free fibular flaps (53 patients) followed by pedicled muscle flaps (31 patients). A total of 72 of 96 patients (75%) achieved independent ambulation, and an additional 19 patients (20%) ambulated with assistance. There were only three (3%) amputations. A total of 13 patients died from metastatic disease (14%). Conclusions Plastic surgery procedures play an increasingly important role in pediatric lower extremity sarcoma reconstruction and functional limb salvage. Published series are limited in number and case volume; to date, no systematic review has been published. The existing data emphasize the role of microvascular free-fibula transfer as well as local muscle flap coverage in preserving limb length and function, with minimal risk of local recurrence and need for amputation.

Reconstruction of partial lumpectomy defects with reduction mammoplasty techniques can improve aesthetic outcomes. However, the impact of the significant tissue rearrangement on postoperative mammographic findings and subsequent recommendations for biopsy has not been well studied. A retrospective review of 64 patients who underwent partial mastectomy with immediate oncoplastic reduction mammoplasty reconstruction from 2001 to 2008 was performed. Mammography reports at 6 months, 1 year, and 2 years postoperatively were reviewed for Breast Imaging Reporting and Data System (BI-RADS) scores, predominant findings, and recommendations for subsequent imaging or biopsy. At 6 months postoperatively, 38 patients had benign findings of postsurgical changes, whereas 5 patients had benign calcifications on mammography. At 1 year, 41 patients continued to have benign mammograms, whereas 8 patients had calcifications. Five patients underwent biopsy; 4 patients revealed benign findings, and one patient revealed recurrent carcinoma. At 2 years, 50 patients had postsurgical changes, 2 patients developed fat necrosis, and 6 patients had calcifications. Two patients required biopsies, both of which demonstrated benign findings. Overall, 89% of the patients required no additional intervention in the 2-year period after oncoplastic reduction mammoplasty. Malignancy was discovered in one patient at 1 year postoperatively, for an overall recurrence rate of 2% at 2 years. Although substantial tissue rearrangement is performed at the time of oncoplastic reduction mammoplasty, our results demonstrate low rates of abnormal postoperative mammograms and subsequent biopsies over the first 2 years after the procedure, supporting this technique as a safe approach to reconstructing defects after partial mastectomy.

Despite the potential aesthetic and psychological benefits of total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex (NAC) skin, there is still reluctance to use the technique due to concern for increased recurrence rates or higher postoperative complication rates. The rapidly expanding literature describing outcomes after TSSM enables a comprehensive review of recurrence rates and surgical complications.Studies describing nipple-sparing or TSSM were identified from the MEDLINE and Cochrane databases. Studies that reported oncologic outcomes and/or data on postoperative complications were included.Twenty-seven studies were identified that met inclusion criteria, representing a total of 3331 mastectomies. Review of oncologic outcomes in the 10 studies (representing 1148 mastectomies) with documented mean/median follow-up of 2 years demonstrated an overall local-regional recurrence rate of 2.8%. Ischemic complications involving the NAC were reported in 24 studies (representing 3091 mastectomies), with 9.1% of cases reported to have some degree of NAC necrosis and 2.0% of cases complicated by complete necrosis leading to NAC loss. Sixteen studies (representing 2213 mastectomies) reported rates of skin flap necrosis, which occurred in 9.5% of cases. Eighty-one percent of the total cases reviewed involved expander-implant reconstruction; in the 16 studies (representing 2343 reconstructions) that reported outcomes after expander-implant reconstruction, overall expander-implant loss was 3.4%.There is now a significant body of literature demonstrating low rates of early local-regional recurrence and postoperative complications after TSSM. These data support the use of TSSM techniques, which improve psychological and aesthetic outcomes without compromising therapeutic efficacy.

c-Jun-N-terminal kinase (JNK) is a signaling molecule that is activated by proinflammatory signals, endoplasmic reticulum (ER) stress, and other environmental stressors. Although JNK has diverse effects on immunological responses and insulin resistance in peripheral tissues, a functional role for JNK in feeding regulation has not been established. In this study, we show that central inhibition of JNK activity potentiates the stimulatory effects of glucocorticoids on food intake and that this effect is abolished in mice whose agouti-related peptide (AgRP) neurons are degenerated. JNK1-deficient mice feed more upon central administration of glucocorticoids, and glucocorticoid receptor nuclear immunoreactivity is enhanced in the AgRP neurons. JNK inhibition in hypothalamic explants stimulates Agrp expression, and JNK1-deficient mice exhibit increased Agrp expression, heightened hyperphagia, and weight gain during refeeding. Our study shows that JNK1 is a novel regulator of feeding by antagonizing glucocorticoid function in AgRP neurons. Paradoxically, JNK1 mutant mice feed less and lose more weight upon central administration of insulin, suggesting that JNK1 antagonizes insulin function in the brain. Thus, JNK may integrate diverse metabolic signals and differentially regulate feeding under distinct physiological conditions.

Leptin is a fat-derived hormone that exerts pleiotropic effects on energy balance and neuroendocrine functions. Mice defective in leptin or its receptor [leptin receptor, isoform b (LepRb)] exhibit profound obesity, infertility, and reduced linear growth. Leptin binding to its receptor triggers multiple signaling pathways, including signal transducer and activator of transcription 3 (Stat 3), phosphatidylinositol-3-kinase, and ERK. A considerable amount of effort has been focused on how these signaling pathways mediate diverse leptin functions. Mice containing a mutant LepRb incapable of Stat3 signaling are obese but remain fertile with enhanced linear growth. In contrast, deletion of Stat3 in the whole brain with Nestin-Cre results in infertility and decreased linear growth, in addition to obesity. The additional phenotypes of the Nestin-mediated deletion could reflect Stat3 action in non-LepRb neurons or leptin-independent Stat3 actions in LepRb neurons. To resolve this discrepancy and to gain more insight into the metabolic actions of Stat3, we have generated mice in which Stat3 is disrupted specifically in LepRb neurons after the onset of leptin receptor expression. We show that mutant mice exhibit profound obesity with increased linear growth and normal fertility. In addition, impaired glycemic control in these animals correlates with their degree of obesity. These results demonstrate that Stat3 in LepRb neurons does not regulate linear growth or fertility. These results further suggest that leptin's effects on growth and reproduction are mediated by other signaling pathways, and that Stat3-mediated control of these functions is mediated independently of leptin and LepRb neurons.