Efficacy of Tranexamic Acid in Reducing Seroma and Hematoma Formation Following Reduction Mammaplasty.

BACKGROUND: Tranexamic acid (TXA) has gained increasing recognition as a valuable pharmacologic agent within plastic surgery. OBJECTIVES: The aim of this study was to investigate the value and safety profile of both intravenous and topically administered TXA in the setting of bilateral reduction mammaplasty. METHODS: A retrospective review was performed to identify consecutive patients who underwent bilateral reduction mammaplasty for symptomatic macromastia (January 2016-July 2021). Pertinent preoperative, intraoperative, and postoperative details were collected/reviewed. Primary outcome measures included hematoma requiring surgical evacuation and clinically significant/symptomatic seroma formation mandating percutaneous aspiration. Patients taking anticoagulation/antiplatelet medication or those with a history of thromboembolic diseases were excluded. Patients who had received TXA were compared to a historical control group who did not receive TXA within the same consecutive cohort. RESULTS: A total of 385 consecutive patients (770 breasts) were included. TXA was used in 514 (66.8%) cases (topical, 318 [61.9%]; intravenous, 170 [33.1%]; intravenous and topical, 26 [5.1%]). Neither seroma nor hematoma were impacted/reduced with TXA (P > 0.05). Increased age (hazards ratio, 1.06 per 1-year increase; 95% CI, 1.004-1.118) significantly increased the risk of hematoma (P = 0.032). The use of drains significantly decreased the risk of seroma (P < 0.0001). Increased BMI increased the risk of seroma (hazards ratio, 1.16 per 1-kg/m2 increase; 95% CI, 1.06-1.26; P = 0.0013). The use of TXA did not impact drain duration. CONCLUSIONS: This study, the largest to date on the use of IV and topical TXA, did not find any reduction in risk when using TXA in breast reduction surgery.

An 11-year Institutional Review of Nipple-Areolar Complex Tattooing for Breast Reconstruction: Identifying Risk Factors for Development of Tattoo-related Infectious Complications.

BACKGROUND: Nipple-areolar complex (NAC) tattooing remains a simple and safe procedure, which complements breast reconstruction. This study reviews 11 years of NAC tattooing to identify risk factors for tattoo-related complications. METHODS: Patients undergoing NAC tattooing from January 2009 to March 2020 were reviewed. Patient information, reconstructive, and tattoo procedural details were analyzed. Tattoo-related breast infections, defined as breast redness requiring antibiotic therapy within 30 days after tattoo, were captured. Patients with reactive breast redness during the first 2 postprocedural days were excluded. RESULTS: Overall, 539 patients (949 breasts) were included. Implant-based reconstruction (IBR) was performed in 73.6% of breasts (n = 698), whereas 26.4% (n = 251) underwent autologous-based reconstruction (ABR). Acellular-dermal matrix was used in 547 breasts (57.6%). There as a 13.7% (n = 130) of breasts that underwent pretattoo radiation. There was a 65.3% (n = 456) of breasts that underwent subpectoral IBR, whereas 34.7% (n = 242) breasts underwent prepectoral IBR. Tattoo-related infection rate was 2.2% (n = 21 breasts). Mean time to infection was 6.5 ± 5.3 days. There was a 85.7% (n = 18) of infections that occurred in IBR patients, one third occurring in radiated patients. There was a 95.2% (n = 20) of infections that were treated with oral antibiotics only. One explantation was performed after failed intravenous antibiotics. On multivariable analysis, radiation history (odds ratio, 4.1, P = 0.007) and prepectoral IBR (odds ratio, 2.8, P = 0.036) were independent predictors of tattoo-related infection. Among irradiated breasts, breasts with IBR had greater odds of developing tattoo-related infection versus breasts with ABR (P = 0.025). CONCLUSIONS: Although tattoo-related infections were uncommon, previous radiation and prepectoral IBR were both found to be independent predictors of tattoo-related breast infection. There is a role for preprocedural prophylactic antibiotics in these patients to mitigate infectious risk.

Risk Factors for Lymphedema after Thigh Sarcoma Resection and Reconstruction.

Secondary lymphedema can be a lifelong and debilitating consequence of lower extremity oncologic resection and reconstruction. The goal of this study was to identify risk factors for the development of lymphedema in patients treated for thigh sarcoma. METHODS: A retrospective review analyzed all patients who underwent thigh sarcoma resection and reconstruction by a plastic surgeon at the Mayo Clinic between 1997 and 2014. Patient demographics, tumor characteristics, surgical management, adjunctive therapies, and complications of patients who did and did not develop postoperative lymphedema were compared. RESULTS: A total of 148 patients were identified. Twelve percent of patients developed lymphedema postoperatively during an average follow-up of 26 months. Risk factors for the development of lymphedema included defect location in the medial thigh (P = 0.04), arterial resection (P = 0.001), arterial reconstruction (P = 0.027), and a history of cardiac disease (P = 0.03). Twenty-two percent of patients who developed lymphedema also experienced wound dehiscence compared with 4.6% of patients without lymphedema (P = 0.02). There were no differences in age, body mass index, smoking, history of deep venous thrombosis or venous stasis, wound dimensions, or type of reconstruction performed in patients with and without lymphedema. CONCLUSIONS: Lymphedema is common following major oncologic resection. Preexisting cardiac disease, tumor location in the medial thigh, and arterial resection and reconstruction were associated with a higher risk of postoperative lymphedema. Noninfectious wound dehiscence may be secondary to lymphedema or represent an early indicator of patients who will ultimately develop lymphedema.

Outcomes of microvascular bone flaps versus osteocutaneous flaps in head and neck reconstruction.

BACKGROUND: Surgical resection of head and neck (H&N) neoplasms requiring osseous reconstruction have underdefined complication profiles. This study aimed to characterize postoperative outcomes of patients with H&N neoplasia undergoing osteocutaneous flap (OCF) or bare bone flap (BBF) reconstructions. MATERIALS AND METHODS: Retrospective analysis of the National Surgical Quality Improvement Program (NSQIP) 2005-2017 databases. Queried for diagnosis and procedural codes extracted patients with H&N neoplasms undergoing BBF or OCF reconstruction. Postoperative complications were evaluated. Multivariable regression generated adjusted odds ratios. RESULTS: A cohort of 746 patients were identified. Of reconstructions, 24.9% (n = 186/746) were BBFs while 75.1% (n = 560/746) were OCFs. 58.1% of the BBF cohort and 59.9% of the OCF cohort experienced an all-cause complication (p = .654). Sub-stratified, 24.2% of BBF and 17.5% of OCF patients experienced a wound complication (p = .045). Regression analysis demonstrated no difference in risk for medical complications between cohorts. However, patients receiving OCFs had a decreased likelihood of developing a wound complication (OR 0.652; 95%CI 0.430-0.989; p = .044) compared to patients receiving BBFs. CONCLUSION: The incidence of complications following osseous reconstruction of the H&N is considerable. Although several complication outcomes do not seem to differ between BBF or OCF reconstructions, OCFs is associated with a decreased likelihood of wound complications.

Complications after thigh sarcoma resection.

BACKGROUND AND OBJECTIVES: Standard treatment for extremity sarcoma is limb-sparing surgery often with radiation, but complications occur frequently. We sought to determine factors predictive of wound complications after thigh sarcoma resection and reconstruction while analyzing trends over time. METHODS: We reviewed all thigh defects requiring plastic surgeon reconstruction following sarcoma resection at our institution from 1997 to 2014. Patient demographics, comorbidities, operative characteristics, multi-modality therapies, and complications were analyzed. Wound complications were: infection, dehiscence, seroma, hematoma, or partial/total flap loss. RESULTS: There were 159 thigh reconstructions followed for 30 months on average. Eighty-seven percent of patients underwent radiation and 42% had chemotherapy. Almost half (49.1%) had a complication. The most common wound complication was surgical site infection (23.3%) followed by dehiscence (19.5%), and seroma (10.7%). Less common were partial (2.5%) or total flap loss (0.6%). Reoperation was required in 21 patients (13.2%). Tobacco use, older patient age, cardiac disease, and higher body mass index were independently associated with wound complications. Complications trended towards decreasing over time, but this was not statistically significant. CONCLUSIONS: Tobacco use, cardiac disease, and higher body mass index, but not the timing of reconstruction, appear to increase the risk of wound complications after thigh soft tissue sarcomas resection and plastic surgery reconstruction.

Institutional Collaboration in Plastic Surgery Research: A Solution to Resource Limitations.

BACKGROUND: The current climate of health care reform and research funding restrictions presents new challenges for academic plastic surgery. Collaboration with private enterprise has been associated with greater research productivity in the general biomedical literature. This study seeks to analyze publication trends in Plastic and Reconstructive Surgery (PRS) to evaluate any changes in institutional collaboration over time. METHODS: Bibliographic data were retrospectively analyzed for all original research and discussion articles published in PRS from 2012 to 2016. The institutional affiliation for each publication was characterized from its author list as solely academic, private, government, or combinations of these (defined here as "institutional collaborations"). Annual National Institutes of Health (NIH) funding data were also collected over the same period, and associations were analyzed by linear regression. RESULTS: In total, 2,595 publications were retrieved from PRS between 2012 and 2016, of which 2,027 (78.1%) originated solely from academic institutions and 411 (15.8%) from institutional collaborations. Although the proportion of academic-only publications decreased from 82% to 74%, the proportion of institutional collaborations increased from 10% to 20% (P = 0.038). Concurrently, NIH funding declined from $33.4 billion to a low of $30.7 billion, which was associated with the decreasing proportion of academic-only publications (P = 0.025) and increasing proportion of institutional collaborations (P = 0.0053). CONCLUSIONS: Traditional sources of academic research funding have been restricted during the politically and financially tumultuous recent years. With no signs of improving access to financial resources from the NIH, academic plastic surgeons may consider diversifying their institutional partnerships to continue pioneering advances in the field.

Treatment of Craniosynostosis: The Impact of Hospital Surgical Volume on Cost, Resource Utilization, and Outcomes.

The authors aim to quantify the impact of hospital volume of craniosynostosis surgery on inpatient complications and resource utilization using national data. Children <12 months with nonsyndromic craniosynostosis who underwent surgery in 2012 at academic hospitals in the United States were identified from the Kids' Inpatient Database (KID) developed by the Healthcare Cost and Utilization Project (HCUP). Hospital craniosynostosis surgery volume was stratified into tertiles based on total annual hospital cases: low volume (LV, 1-13), intermediate volume (IV, 14-34), and high volume (HV, ≥35). Outcomes of interest include major complications, blood transfusion, charges, and length of stay (LOS). In 2012, 154 hospitals performed 1617 total craniosynostosis surgeries. Of these 580 cases (35.8%) were LV, 549 cases (33.9%) were IV, and 488 cases (30.2%) were HV. There was no difference in major complications between hospital volume tertiles (4.3% LV; 3.8% IV; 3.1% HV; P = 0.487). The highest blood transfusion rates were seen at LV hospitals (47.8% LV; 33.9% IV; 26.2%; P < 0.001). Hospital charges were lowest at HV hospitals ($55,839) compared with IV hospitals ($65,624; P < 0.001) and LV hospitals ($62,325; P = 0.005). Mean LOS was shortest at HV hospitals (2.96 days) compared with LV hospitals (3.31 days; P = 0.001); however, there was no difference when compared with IV hospitals (3.07 days; P = 0.282). Hospital case volume may be an important associative factor of blood transfusion rates, LOS, and hospital charges; however, there is no difference in complication rates. These results may be used to guide quality improvement within the surgical management of craniosynostosis.

Immediate Breast Reconstruction among Patients with Medicare and Private Insurance: A Matched Cohort Analysis.

BACKGROUND: By eliminating economic hurdles, the Women's Health and Cancer Rights Act of 1998 represented a paradigm shift in the availability of breast reconstruction. Yet, studies report disparities among Medicare-insured women. These studies do not account for the inherent differences in age and comorbidities between a younger privately insured and an older Medicare population. We examined immediate breast reconstruction (IBR) utilization between a matched pre- and post-Medicare population. METHODS: Using the Nationwide Inpatient Sample database (1992-2013), breast cancer patients undergoing IBR were identified. To minimize confounding medical variables, 64-year-old privately insured women were compared with 66-year-old Medicare-insured women. Demographic data, IBR rates, and complication rates were compared. Trend over time was plotted for both cohorts. RESULT: A total of 21,402 64-year-old women and 25,568 66-year-old women were included. Both groups were well matched in terms of demographic type of reconstruction and complication rates. 72.3% of 64-year-old and 71.2 of % 66-year-old women opted for mastectomy. Of these, 25.5% (n = 3,941) of 64-year-old privately insured and 17.7% (n = 3,213) of 66-year-old Medicare-insured women underwent IBR (P < 0.01). During the study period, IBR rates increased significantly in both cohorts in a similar cohort. CONCLUSION: This study demonstrates significant increasing IBR rates in both cohorts. Moreover, after an initial slower upward trend, after a decade, IBR in 66-year-old Medicare-insured women approached similar rates of breast reconstruction among those with private insurance. Trends in unilateral versus bilateral mastectomy are also seen.

Umbilical necrosis rates after abdominal-based microsurgical breast reconstruction.

BACKGROUND: Umbilical stalk necrosis represents a rare, yet important complication after abdominal-based microsurgical breast reconstruction, which is both underrecognized and understudied in the literature. Once identified, umbilical reconstruction can be an extremely challenging problem. METHODS: All consecutive breast free flaps at a single institution from February 2004 to February 2016 were reviewed, excluding non-abdominal-based flaps. Patients were divided based on the development of umbilical necrosis postoperatively. Demographics, surgical characteristics, and other complications were compared between the groups. RESULTS: A total of 918 patients met the inclusion criteria, with 29 developing umbilical necrosis identified (3.2%). Patients developing necrosis tended to be older (49.4 yrs versus 52.9 yrs; P < 0.01); have higher BMI (31.3 versus 27.8; P < 0.01); and were more likely to be smokers (27.5% versus 11.6%; P = 0.01). Umbilical necrosis was also associated with increased flap weight (830 g versus 656 g; P < 0.01), decreased time of perforator dissection (151 min versus 169 min; P = 0.02); bilateral cases (68.9% versus 44.7%; P < 0.01), and increased number of perforators per flap (2.5 versus 2.2; P = 0.03). There was no association with flap type (deep inferior epigastric perforator, superficial inferior epigastric artery, or free TRAM), diabetes, previous abdominal surgery, or use of preoperative imaging. Umbilical necrosis was not associated with any concomitant complications. CONCLUSIONS: Umbilical stalk necrosis was found to occur in 3.2% of patients and was associated with several preoperative comorbidities and intraoperative characteristics. This information should help influence intraoperative decision-making to prevent the development of this undesirable complication.

Prevalence of psychiatric comorbidities among women undergoing free tissue autologous breast reconstruction.

BACKGROUND AND OBJECTIVES: Autologous breast reconstruction (BR) can be a stressful life event. Therefore, women undergoing mastectomy and autologous BR are required to have sufficient coping mechanisms. Although mental health problems are widespread, information regarding the prevalence of psychiatric diagnosis among these patients is scarce. METHODS: Retrospective analysis was performed using data from a large tertiary teaching hospital and the Nationwide Inpatient Sample (NIS) database. Patients undergoing autologous BR after mastectomy were included and evaluated for psychiatric disorders. Prevalence of each disorder, timing of diagnosis (preoperative or postoperative), and data per age group were reviewed. RESULTS: Between 2004 and 2014, 817 patients were included from the institutional database and 26 399 from the NIS database. Preoperatively, 15.3% of the patients were diagnosed with a psychiatric disorder within our institution and 17.6% nationwide (P < 0.001). Postoperatively, 20.5% of the institutional patients were diagnosed with a psychiatric disorder. No major differences in prevalence were seen between age groups. CONCLUSIONS: Approximately, one in six patients were diagnosed with a psychiatric comorbidity preoperatively. Postoperatively, an additional 20.5% developed a psychiatric disorder. There was no difference in prevalence and timing of diagnosis between age groups.

Trends in immediate breast reconstruction and early complication rates among older women: A big data analysis.

BACKGROUND: Although approximately 57% of breast cancer (BC) diagnoses are in older patients (>60 years), only 4.1-14% receives breast reconstruction (BR). This has been attributed to physician concerns about operative complications. This paper aims to: 1) analyze the 30-day complication rates in the older patient population undergoing immediate breast reconstruction (IBR); and 2) analyze links between complication type and category of reconstruction. METHODS: Using the ACS-NSQIP database (2005-2014), all women older than 60 years of age diagnosed with BC and DCIS were identified. IBR and complication rates were plotted for all ages. Patients were divided into those with and those without complications. Patient demographics and co-morbidities were compared. Complications within each type of reconstruction were analyzed. RESULTS: Of the 4450 BC and 1104 DCIS patients, 22.3% (BC) and 20.9% (DCIS) had complications. IBR decreased significantly with increased age (P < 0.00 in both cohorts), while complication rates remained stable across all ages (P = 0.32 in BC, P = 0.69 in DCIS patients). Patients were well matched in terms of demographics. CONCLUSIONS: The rates of breast reconstruction decrease with increasing age. Despite increasing age, associated complication rates in IBR patients remained stable.

Medial Row Perforators Are Associated with Higher Rates of Fat Necrosis in Bilateral DIEP Flap Breast Reconstruction.

BACKGROUND: The purpose of this study was to evaluate perfusion-related complications in bilateral deep inferior epigastric perforator (DIEP) flap breast reconstruction based on perforator selection. METHODS: A retrospective review of a prospectively maintained database was performed on all patients undergoing bilateral DIEP flap reconstruction at a single institution between 2004 and 2014. The hemiflaps were separated into three cohorts based on perforator location: lateral row only, medial row only, and medial plus lateral rows. Postoperative flap-related complications were compared and analyzed. RESULTS: There were 728 total hemiflaps: 263 (36.1 percent) based on the lateral row, 225 (30.9 percent) based on the medial row, and 240 (33.0 percent) based on both the medial and lateral rows. The groups were well matched by perforator number and flap weight. Fat necrosis occurrence was significantly higher in flaps based solely on the medial row versus lateral row perforators (24.5 percent versus 8.2 percent; p < 0.001). There was no statistically significant difference in fat necrosis between flaps based only on the lateral row versus flaps based on both the medial and lateral rows (8.2 percent versus 11.6 percent; p = 0.203). Generally, within the same row, increasing the number of perforators decreased the incidence of fat necrosis. CONCLUSIONS: Perforator selection is critical for minimizing perfusion-related flap complications. In bilateral DIEP flaps, lateral row-based perforators result in significantly less fat necrosis than medial row-based perforators. The authors' data suggest that the addition of a lateral row perforator to a dominant medial row perforator may decrease the risk of fat necrosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Membrane Protein Quantity Control at the Endoplasmic Reticulum.

The canonical function of the endoplasmic reticulum-associated degradation (ERAD) system is to enforce quality control among membrane-associated proteins by targeting misfolded secreted, intra-organellar, and intramembrane proteins for degradation. However, increasing evidence suggests that ERAD additionally functions in maintaining appropriate levels of a subset of membrane-associated proteins. In this 'quantity control' capacity, ERAD responds to environmental cues to regulate the proteasomal degradation of specific ERAD substrates according to cellular need. In this review, we discuss in detail seven proteins that are targeted by the ERAD quantity control system. Not surprisingly, ERAD-mediated protein degradation is a key regulatory feature of a variety of ER-resident proteins, including HMG-CoA reductase, cytochrome P450 3A4, IP3 receptor, and type II iodothyronine deiodinase. In addition, the ERAD quantity control system plays roles in maintaining the proper stoichiometry of multi-protein complexes by mediating the degradation of components that are produced in excess of the limiting subunit. Perhaps somewhat unexpectedly, recent evidence suggests that the ERAD quantity control system also contributes to the regulation of plasma membrane-localized signaling receptors, including the ErbB3 receptor tyrosine kinase and the GABA neurotransmitter receptors. For these substrates, a proportion of the newly synthesized yet properly folded receptors are diverted for degradation at the ER, and are unable to traffic to the plasma membrane. Given that receptor abundance or concentration within the plasma membrane plays key roles in determining signaling efficiency, these observations may point to a novel mechanism for modulating receptor-mediated cellular signaling.

Hexamethylene amiloride engages a novel reactive oxygen species- and lysosome-dependent programmed necrotic mechanism to selectively target breast cancer cells.

Anticancer chemotherapeutics often rely on induction of apoptosis in rapidly dividing cells. While these treatment strategies are generally effective in debulking the primary tumor, post-therapeutic recurrence and metastasis are pervasive concerns with potentially devastating consequences. We demonstrate that the amiloride derivative 5-(N,N-hexamethylene) amiloride (HMA) harbors cytotoxic properties particularly attractive for a novel class of therapeutic agent. HMA is potently and specifically cytotoxic toward breast cancer cells, with remarkable selectivity for transformed cells relative to non-transformed or primary cells. Nonetheless, HMA is similarly cytotoxic to breast cancer cells irrespective of their molecular profile, proliferative status, or species of origin, suggesting that it engages a cell death mechanism common to all breast tumor subtypes. We observed that HMA induces a novel form of caspase- and autophagy-independent programmed necrosis relying on the orchestration of mitochondrial and lysosomal pro-death mechanisms, where its cytotoxicity was attenuated with ROS-scavengers or lysosomal cathepsin inhibition. Overall, our findings suggest HMA may efficiently target the heterogeneous populations of cancer cells known to reside within a single breast tumor by induction of a ROS- and lysosome-mediated form of programmed necrosis.