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Introduction: Post-mastectomy radiation therapy (PMRT) is an important adjuvant treatment in patients with locally advanced breast cancer, shown to decrease the rate of locoregional recurrence and improve overall survival. Autologous breast reconstruction is the standard-of-care in patients who require PMRT. However, there is no clear superior approach regarding the optimal timing of reconstruction in these patients. Our goal was to compare outcomes between patients who underwent autologous reconstruction either before or after undergoing PMRT. Methods: We performed a retrospective chart review of patients who underwent all stages of mastectomy, autologous reconstruction, and PMRT at UCSF between 2015 and 2021. Clinical and surgical characteristics and complications were collected and assessed. We then matched these patients by age, BMI and autologous reconstruction type to a cohort of patients who underwent both mastectomy and autologous reconstruction at UCSF who did not require PMRT. Groups were compared by both timing of and receipt of radiation. Results: Nineteen patients underwent mastectomy, autologous reconstruction, and PMRT at UCSF between 2015 and 2021. Thirteen of these patients underwent reconstruction after receiving PMRT, while six of these patients underwent reconstruction followed by PMRT. These nineteen patients were matched by age, BMI and flap type to a cohort of 19 patients who underwent mastectomy and autologous reconstruction at UCSF. The cumulative early complication rate was 16% in the radiated group and 21% in the non-radiated group. This included infection requiring IV antibiotics, hematoma, wound breakdown, mastectomy flap necrosis, and arterial or venous thrombosis [see Table 1 for breakdown by group]. No flap loss occurred in any group. Fat necrosis was observed in 16% of radiated patients and 11% of non-radiated patients. Revision rates were equal between the radiated and non-radiated groups at 58% (including currently planned revisions). There was no strong correlation between complication rate and either total radiation dose or time between radiation and reconstruction (r=-0.5 and r=-0.1). Discussion: Complication rates between all groups were similar. Notably, the only observed infections, both requiring admission and IV antibiotics, occurred in the pre-reconstruction PMRT group. Given the potential for tissue expander infection and increased number of outpatient visits, further investigation is warranted in immediate autologous reconstruction in those patients who require PMRT, not only to decrease the hospital and patient burden, but to improve patient satisfaction. Larger cohort studies are required to draw further conclusions on the effect of PMRT and timing of autologous reconstruction, and to investigate patient-reported outcomes. Table 1.Complication rate by groupComplicationRadiated. Pre-recon PMRT. Post-recon PMRTNon-radiatedCumulative early complications16%. 15%. 17%21%Infection11%. 16%. 0%0%Hematoma0%. 0%. 0%5%Wound breakdown11%. 8%. 17%5%Mastectomy flap necrosis5%. 0%. 17%11%Arterial or venous thrombosis0%. 0%. 0%5%Fat necrosis16%. 15%. 17%11%Revision58%. 62%. 50%58% Citation Format: Laura Barnes, Deborah Martins, Merisa Piper. Timing of post-mastectomy radiation therapy and autologous reconstruction outcomes: A retrospective review [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-21-03.

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.

Development of the nipple-sparing mastectomy (NSM) technique has dramatically improved breast reconstruction, and preservation of the nipple-areolar complex (NAC) positively influences patient satisfaction. However, women with large, ptotic breasts have historically not been candidates for NAC preservation due to impaired perfusion of the NAC leading to NAC loss. Although reduction mammoplasty has been reported as a strategy to increase candidacy for NSM, success rates and surgical outcomes for this staged approach are not well described in heterogeneous clinical scenarios.MethodsWe performed a retrospective chart review of all patients who underwent reduction mammoplasty followed by NSM at our institution between January 2014 and September 2020. Clinical and surgical characteristics were collected. All surgical complications, including NAC loss rates, were analyzed.ResultsForty-one patients (74 breasts) underwent staged NSM during the defined time period. The average time between breast reduction mammoplasty and NSM was 213 days. Overall, 94.6% of NSM resulted in successful nipple preservation. There was no significant difference in the time interval from breast reduction mammoplasty to NSM between patients who had NAC loss (208 days) and those who did not (213 days, P = 0.87). Increasing age was significantly associated with risk of NAC loss (P = 0.002) in our cohort.ConclusionsIn women with breast ptosis (which precludes safe NSM), it is possible to first offer reduction mammoplasty to preserve the NAC for future NSM. Our data suggest that 3 months between staged procedures is a safe time frame.

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. 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 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.

Summary Lymphocytes in barrier tissues play critical roles in host defense and homeostasis. These cells take up residence in tissues during defined developmental windows, when they may demonstrate distinct phenotypes and functions. Here, we utilized mass and flow cytometry to elucidate early features of human skin immunity. Although most conventional αβ T (Tconv) cells in fetal skin have a naive, proliferative phenotype, a subset of CD4+ Tconv and CD8+ cells demonstrate memory-like features and a propensity for interferon (IFN)γ production. Skin regulatory T cells dynamically accumulate over the second trimester in temporal and regional association with hair follicle development. These fetal skin regulatory T cells (Tregs) demonstrate an effector memory phenotype while differing from their adult counterparts in expression of key effector molecules. Thus, we identify features of prenatal skin lymphocytes that may have key implications for understanding antigen and allergen encounters in utero and in infancy., Graphical Abstract, Highlights CyTOF reveals a complex lymphocyte landscape in developing human skin Developing skin contains CD45RO+ conventional T cells with propensity to produce IFNγ Regulatory T cells (Tregs) in skin before birth display effector memory properties Skin Tregs increase in conjunction with initial hair follicle morphogenesis, Dhariwala et al. utilize mass and flow cytometry to elucidate distinguishing features of lymphocytes in developing fetal skin. The early presence of memory-like subsets among conventional and regulatory T cells may have key implications for understanding nascent cutaneous immune function.

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.

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.

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: Evaluating the size of invasive lobular carcinoma of the breast (ILC) poses a challenge due to higher rates of false negatives compared to invasive ductal carcinoma. Magnetic resonance imaging (MRI) is often considered the best imaging modality for ILC, but requires additional cost, time, and the use of intravenous contrast, unlike ultrasonography (U/S). We sought to determine whether U/S might provide sufficient information to evaluate response to therapy, thus enabling the use of U/S for surgical planning after NAT in ILC. Methods: We queried a database of 685 ILC cases at UCSF between 1981 and 2018, identifying all cases receiving NAT. We reviewed MRI and U/S reports and collected longest tumor diameter and imaging features. We used t-test, chi-squared test, and Pearson’s correlation to compare U/S and MRI longest diameter to true size on pathology. Data were evaluated in Stata 14.2. Results: 148 patients treated with NAT were identified. Of these, 84 (56.8%) received neoadjuvant chemotherapy and 64 (43.2%) received neoadjuvant endocrine therapy. Compared to the endocrine therapy group, those receiving chemotherapy were significantly younger (mean age 53.3 years vs. 62.8 years, p=0.0002), more likely to have tumors of the ER-PR-HER2- or HER2+ subtypes (p=0.016), and of higher pathologic stage (p=0.024). Among 43 cases with evaluable data, longest tumor diameter on post-treatment U/S strongly correlated with longest diameter on post-treatment MRI (r=0.93, p Conclusions: Post-treatment MRI longest diameter and post-treatment U/S longest diameter were strongly correlated. The presence of NME on pre-treatment MRI meant that post-treatment U/S was no longer a useful predictor of true tumor size, but when NME was not present, post treatment U/S longest diameter was significantly correlated with true size. Therefore, for ILC patients with no NME on pre- treatment MRI, these findings suggest that treatment response evaluation of tumor size can be done with U/S only. Future work will explore the ability of U/S to determine nodal response compared to MRI. Additionally, MRI features such as functional tumor volume may provide additional response information beyond longest diameter, and ongoing research is needed. Table 1: Characteristics of study population.Neoadjuvant chemotherapy (n=84)Neoadjuvant endocrine therapy (n=64)P-valueMean age, range53.3 (29-81)62.8 (41-89)0.0002Biomarker and receptor status0.016ER+PR+HER2-41 (54.7%)35 (62.5%)ER+PR-HER2-19 (25.33%)20 (35.7%)ER-PR-HER2-4 (5.33%)0HER2+11 (14.7%)1 (1.8%)Grade0.11122 (27.9%)24 (37.5%)250 (63.3%)29 (60.9%)37 (8.9%)1 (1.56%)Pathologic stage0.024I30 (35.7%)34 (53.1%)II36 (42.9%)14 (21.9%)III18 (21.4%)16 (25.0%)Mean follow-up time (years, 95% confidence interval)5.9 (4.9-6.9)5.1 (4.2-6.1)0.15 Citation Format: Kelly Fahrner-Scott, Jasmine M Wong, Merisa Piper, Cheryl Ewing, Michael Alvarado, Laura J Esserman, Nola Hylton, Rita A Mukhtar MD. Accuracy of ultrasound in evaluating response to neoadjuvant therapy in invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD9-08.

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.

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.

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.