When a Good Flap Turns Bad: A Temporal Predictive Model for Free Flap Complications.

BACKGROUND: Microsurgical cases are complex plastic surgery procedures with a significant risk of acute postoperative complications. In this study, we use a large-scale database to investigate the temporal progression of complications after microsurgical procedures and the risk imparted by acute postoperative complications on subsequent reconstructive outcomes. METHODS: Microsurgery cases were extracted from the National Surgical Quality Improvement Program database by Current Procedural Terminology codes. Postoperative complications were collected for 30 days after surgery and stratified into four temporal periods (postoperative days [PODs] 0-6, 7-13, 14-20, 21-30). Postoperative complication occurrences were incorporated into a weighted multivariate logistic regression model to identify significant predictors of adverse outcomes (p < 0.05). Separately, a regression model was calculated for the time between index operation and reoperation and additional complications. RESULTS: The final cohort comprised 19,517 patients, 6,140 (31.5%) of which experienced at least one complication in the first 30 days after surgery. The occurrence of prior complications in the postoperative period was a significant predictor of future adverse outcomes following the initial week after surgery (p < 0.001). Upon predictive analysis, overall model performance was highest in PODs 7 to 13 (71.1% accuracy and the area under a receiver operating characteristic curve 0.684); 2,578 (13.2%) patients underwent at least one reoperation within the first 2 weeks after surgery. The indication for reoperation (p < 0.001) and number of days since surgery (p = 0.0038) were significant predictors of future complications after reoperation. CONCLUSION: Prior occurrence of complications in an earlier postoperative week, as well as timing and nature of reoperation, were shown to be significant predictors of future complications.

Financial (dis)incentives to surgical management of head and neck cancer care.

BACKGROUND: Patients with head and neck cancer (HNC) often require complex surgical reconstruction. This retrospective, cross-sectional study compares financial factors influencing HNC and breast cancer (BC) care to examine care disparities. METHODS: Pricing data from 2012 to 2021 was abstracted from the CMS Physician Fee Schedule Look-Up Tool. Nonprofit and research support was quantified by searching the NIH, IRS, and GuideStar databases. New York State Department of Health data from 2015 to 2019 was analyzed to compare costs, charges, and payer mix. RESULTS: HNC reconstructive procedures reimburse lower than comparable breast procedures (p < 0.05). Nonprofit and research support for HNC is disproportionately low relative to disease burden. Patients hospitalized for HNC surgical procedures generated higher costs and lower charges than patients with BC (p < 0.05). CONCLUSION: Comparatively low procedure reimbursement, low nonprofit support, and high cost of care for patients with HNC relative to patients with BC may contribute to care disparities for patients with HNC.

Pregnancy-Associated Breast Changes after Nipple-Sparing Mastectomy.

BACKGROUND: Women of reproductive age are chronically underrepresented in breast cancer studies. Recent studies suggest that almost 40% of patients diagnosed with breast cancer who are of reproductive age want to have children after completing treatment. In this study, the authors evaluated patients of reproductive age who had undergone nipple-sparing mastectomy (NSM) and implant-based reconstruction. The authors compared those who became pregnant with those who did not with respect to clinical and radiologic changes that are reported at follow-up. METHODS: Any patient 45 years of age or younger at the time of NSM was determined to be of reproductive age, selected for evaluation, and followed prospectively. The presence or absence of breast examination changes in the setting of pregnancy after NSM was recorded. RESULTS: A total of 36 patients became pregnant after NSM, and 158 patients did not become pregnant after NSM. Of those who became pregnant, nearly half reported some clinical change just before or immediately after delivery. These changes included color change and discharge at the residual nipple-areola complex and palpable nodularity elsewhere. For those with palpable changes, an ultrasound was performed and hypoechoic lesions with variable vascularity were identified. For those who went on to excision, lactational hyperplasia was the most common diagnosis. CONCLUSIONS: Ultrasound is an appropriate first-line investigation of breast changes, which can include hyperplasia of remaining ductal and glandular tissue. Patients who became pregnant after NSM commonly had clinical breast examination changes, but the majority of these changes were found to be benign on further evaluation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

A Novel Mangled Upper Extremity Injury Assessment Score.

Managing mangled upper extremity injuries is a challenging problem because multiple tissue components including soft tissue, muscle, tendon, bone, nerves, and vessels are involved. The complexity of these injuries has hindered the development of accurate scoring systems and treatment algorithms. METHODS: Patients with mangled upper extremities presenting to a metropolitan level 1 trauma center in New York City over a 10-year period were identified. A mangled upper extremity was defined as any injury to ≥3 tissue components involving the extremity proximal to the digit. RESULTS: The injuries and outcomes of 76 patients were evaluated and used to create a Mangled Upper Extremity Score (MUES). One point was assigned for each of the following injury characteristics: patient age >40, fasciotomy needed, bony fixation required, bony defect present, revascularization required, crush injury mechanism, degloving or avulsion injury present, and a soft tissue defect >50 cm2. The MUES correlated with the number of complications (P value = 1.96 × 10-7) and length of hospital stay (P value = 3.95 × 10-7). Next, a Mangled Extremity Severity Score (MESS) equivalent was calculated for each patient. There was no correlation between the MESS and the number of complications (P value = 0.92) or length of hospital stay (P value = 0.35). CONCLUSIONS: Existing extremity scoring systems, including the MESS, are not reliable in predicting the success of limb salvage attempts or outcomes of mangled upper extremity injuries. The MUES developed in this study correlates significantly with important outcome measures including the number of hospital complications and length of hospital stay.

Decellularized Lymph Nodes as Scaffolds for Tissue Engineered Lymph Nodes.

BACKGROUND: The lymphatic system is commonly injured during cancer treatment. However, despite the morbidity of these injuries, there are currently no options for replacing damaged lymphatics. The purpose of this study was to optimize methods for decellularization of murine lymph nodes (LN) and to determine if these scaffolds can be used to tissue engineer lymph node-like structures. METHODS AND RESULTS: LNs were harvested from adult mice and subjected to various decellularization protocols. The degree of decellularization and removal of nuclear material was analyzed histologically and quantitatively using DNA isolation. In addition, we analyzed histological architecture by staining for matrix proteins. After the optimal method of decellularization was identified, decellularized constructs were implanted in the renal capsule of syngeneic or allogeneic recipient mice and analyzed for antigenicity. Finally, to determine if decellularized constructs could deliver lymphocytes to recipient animals, the matrices were repopulated with splenocytes, implanted in submuscular pockets, and harvested 14 days later. Decellularization was best accomplished with the detergent sodium dodecyl sulfate (SDS), resulting in negligible residual cellular material but maintenance of LN architecture. Implantation of decellularized LNs into syngeneic or allogeneic mice did not elicit a significant antigenic response. In addition, repopulation of decellularized LNs with splenocytes resulted in successful in vivo cellular delivery. CONCLUSIONS: We show, for the first time, that LNs can be successfully decellularized and that these matrices have preserved extracellular matrix architecture and the potential to deliver leukocytes in vivo. Future studies are needed to determine if tissue engineered lymph nodes maintain immunologic function.

Lymph node transplantation results in spontaneous lymphatic reconnection and restoration of lymphatic flow.

BACKGROUND: Although lymph node transplantation has been shown to improve lymphatic function, the mechanisms regulating lymphatic vessel reconnection and functional status of lymph nodes remains poorly understood. METHODS: The authors developed and used LacZ lymphatic reporter mice to examine the lineage of lymphatic vessels infiltrating transferred lymph nodes. In addition, the authors analyzed lymphatic function, expression of vascular endothelial growth factor (VEGF)-C, maintenance of T- and B-cell zone, and anatomical localization of lymphatics and high endothelial venules. RESULTS: Reporter mice were specific and highly sensitive in identifying lymphatic vessels. Lymph node transfer was associated with rapid return of lymphatic function and clearance of technetium-99 secondary to a massive infiltration of recipient mouse lymphatics and putative connections to donor lymphatics. T- and B-cell populations in the lymph node were maintained. These changes correlated with marked increases in the expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Newly formed lymphatic channels in transferred lymph nodes were in close anatomical proximity to high endothelial venules. CONCLUSIONS: Transferred lymph nodes have rapid infiltration of functional host lymphatic vessels and maintain T- and B-cell populations. This process correlates with increased endogenous expression of VEGF-C in the perinodal fat and infiltrating lymphatics. Anatomical proximity of newly formed lymphatics and high endothelial venules supports the hypothesis that lymph node transfer can improve lymphedema by exchanges with the systemic circulation.

Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes.

INTRODUCTION: Obesity is a major cause of morbidity and mortality resulting in pathologic changes in virtually every organ system. Although the cardiovascular system has been a focus of intense study, the effects of obesity on the lymphatic system remain essentially unknown. The purpose of this study was to identify the pathologic consequences of diet induced obesity (DIO) on the lymphatic system. METHODS: Adult male wild-type or RAG C57B6-6J mice were fed a high fat (60%) or normal chow diet for 8-10 weeks followed by analysis of lymphatic transport capacity. In addition, we assessed migration of dendritic cells (DCs) to local lymph nodes, lymph node architecture, and lymph node cellular make up. RESULTS: High fat diet resulted in obesity in both wild-type and RAG mice and significantly impaired lymphatic fluid transport and lymph node uptake; interestingly, obese wild-type but not obese RAG mice had significantly impaired migration of DCs to the peripheral lymph nodes. Obesity also resulted in significant changes in the macro and microscopic anatomy of lymph nodes as reflected by a marked decrease in size of inguinal lymph nodes (3.4-fold), decreased number of lymph node lymphatics (1.6-fold), loss of follicular pattern of B cells, and dysregulation of CCL21 expression gradients. Finally, obesity resulted in a significant decrease in the number of lymph node T cells and increased number of B cells and macrophages. CONCLUSIONS: Obesity has significant negative effects on lymphatic transport, DC cell migration, and lymph node architecture. Loss of T and B cell inflammatory reactions does not protect from impaired lymphatic fluid transport but preserves DC migration capacity. Future studies are needed to determine how the interplay between diet, obesity, and the lymphatic system modulate systemic complications of obesity.

Mechanisms of lymphatic regeneration after tissue transfer.

INTRODUCTION: Lymphedema is the chronic swelling of an extremity that occurs commonly after lymph node resection for cancer treatment. Recent studies have demonstrated that transfer of healthy tissues can be used as a means of bypassing damaged lymphatics and ameliorating lymphedema. The purpose of these studies was to investigate the mechanisms that regulate lymphatic regeneration after tissue transfer. METHODS: Nude mice (recipients) underwent 2-mm tail skin excisions that were either left open or repaired with full-thickness skin grafts harvested from donor transgenic mice that expressed green fluorescent protein in all tissues or from LYVE-1 knockout mice. Lymphatic regeneration, expression of VEGF-C, macrophage infiltration, and potential for skin grafting to bypass damaged lymphatics were assessed. RESULTS: Skin grafts healed rapidly and restored lymphatic flow. Lymphatic regeneration occurred beginning at the peripheral edges of the graft, primarily from ingrowth of new lymphatic vessels originating from the recipient mouse. In addition, donor lymphatic vessels appeared to spontaneously re-anastomose with recipient vessels. Patterns of VEGF-C expression and macrophage infiltration were temporally and spatially associated with lymphatic regeneration. When compared to mice treated with excision only, there was a 4-fold decrease in tail volumes, 2.5-fold increase in lymphatic transport by lymphoscintigraphy, 40% decrease in dermal thickness, and 54% decrease in scar index in skin-grafted animals, indicating that tissue transfer could bypass damaged lymphatics and promote rapid lymphatic regeneration. CONCLUSIONS: Our studies suggest that lymphatic regeneration after tissue transfer occurs by ingrowth of lymphatic vessels and spontaneous re-connection of existing lymphatics. This process is temporally and spatially associated with VEGF-C expression and macrophage infiltration. Finally, tissue transfer can be used to bypass damaged lymphatics and promote rapid lymphatic regeneration.