A Review of 559 Sternal Wound Reconstructions at a Single Institution: Indications and Outcomes for Combining an Omental Flap With Bilateral Pectoralis Major Flaps in a Subset of 17 Patients With Infections Extending Into the Deep Mediastinum.

BACKGROUND: Sternal wound infection (SWI) and dehiscence after median sternotomy for cardiac surgery remain challenging clinical problems with high morbidity. Bilateral pectoralis major myocutaneous flaps are excellent for most sternal wounds but do not reach deeper mediastinal recesses. The omental flap may be a useful adjunct for addressing these deeper mediastinal infections. METHODS: Records of 598 sternal wound reconstructions performed by a single surgeon (J.A.A.) from 1996 to 2022 were reviewed. At the time of surgery, patients underwent sternal hardware removal, debridement, and closure with bilateral pectoralis major myocutaneous flaps. Pedicled omental flaps were also mobilized when additional vascularized tissue was required within the deeper mediastinum. RESULTS: Complete data were available for 559 sternal wound reconstructions performed by the senior author during this period. Bilateral pectoralis and omental flaps were mobilized in 17 of 559 (3.04%) patients. Common indications for initial cardiac surgery included repair or replacement of diseased aortic roots (9/17; 52.94%), aortic valves (8/17; 47.06%), and mitral valves (6/17; 35.29). Mean American Society of Anesthesiologists score was 3.56. Preoperative morbidity included culture-positive wound infection (12/17; 70.59%), dehiscence (15/17; 88.24%), wound drainage (11/17; 64.71%), and inability to close the chest after the original sternotomy because of hemodynamic instability (6/17; 35.29%). Intraoperative deep mediastinal or bone cultures were positive in 8 of 17 (47.06%) patients. Postoperative complications included partial dehiscence (2/17; 11.76%), skin edge necrosis (1/17; 5.88%), seroma (1/17; 5.88%), abdominal hernia (1/17; 5.88%), and recurrent infection (2/17; 11.76%). Three patients (17.65%) died within 30 days of the reconstruction surgery. CONCLUSIONS: Patients undergoing combined pectoralis major and omental flap closure frequently had a history of aortic root and valve disease, and other significant preoperative morbidities. However, postoperative complication rates after combined flap closure were relatively low. Combined pectoralis major and omental flap reconstruction thus appears to be an effective intervention in patients with sternal wounds extending into the deep mediastinum.

An Analysis of 400 Sternal Wound Reconstructions at a Single Institution: Bacterial Pathogens Vary With Time.

BACKGROUND: Sternal wound (SW) infection and dehiscence after median sternotomy from cardiac surgery remain challenging complications with high morbidity. Knowledge of common pathogen types and variance with time from cardiac surgery can simplify the choice of antibiotics while awaiting definitive culture results. METHODS: Records of 505 patients undergoing SW reconstruction by the senior author from 1996 to 2018 at a high-volume cardiac surgery center were reviewed. The most common indications for reconstruction were SW infection and dehiscence. At surgery, all patients underwent removal of sternal hardware, thorough debridement, and closure with bilateral pectoralis major myocutaneous advancement flaps. Deep tissue and bone cultures were sent in nearly all cases. Patients were split into group 1 or group 2 based on timing of flap reconstruction after initial cardiac surgery: 0 to 30 days and longer than 30 days, respectively. RESULTS: Complete data were available for 400 SW procedures performed during this period. Group 1 included 203 patients, and group 2 had 197 patients, with a mean time to SW surgery of 16.3 and 138.1 days, respectively. Intraoperative cultures were positive in 147 of 203 (72.4%), and 122 of 197 (61.9%) patients, respectively. Forty-four patients grew polymicrobial cultures. There was a significant difference in culture positivity rates in the 2 groups (P = 0.0004). The most common bacteria cultured in group 1 was Staphylococcus epidermidis (54 of 203 vs 21 of 197; P < 0.0001), whereas methicillin-sensitive Staphylococcus aureus was most common in group 2 (15 of 203 vs 22 of 197; P = 0.23). Methicillin-resistant S. aureus was relatively common in both groups (17 of 203 vs 21 of 197; P = 0.50). Although not statistically significant, Pseudomonas, Klebsiella, and Candida were all found in a higher percentage of patients in group 2 (p = 0.11, 0.20, 0.20). CONCLUSIONS: Microbial species cultured in SW flap reconstruction vary over time. Staphylococcus epidermidis is the most common infectious agent in patients having reconstruction within 30 days of cardiac surgery, whereas methicillin-sensitive S. aureus is most common after 30 days. The trend toward a higher incidence of Gram-negative and fungal organisms after 30 days may indicate a need for broader initial anti-infective coverage in this patient group. Awareness of these pathogen patterns can better inform antibiotic selection while awaiting culture data.

A Systematic Review of the Orthoplastic Approach in Adult Lower Extremity Soft Tissue Sarcoma Flap Reconstruction.

BACKGROUND: The orthoplastic approach to patient care has changed the way patients with a wide variety of lower extremity pathology are treated. Through a systematic review, we aim to analyze outcomes in adult patients with lower extremity soft tissue sarcomas who undergo an orthoplastic flap management approach to their care. METHODS: A systematic review of adult lower extremity soft tissue sarcoma excision with plastic surgery flap reconstruction was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines searching the Pubmed, Embase, and Web of Science databases from inception to April 2023. RESULTS: After removal of duplicates, title and abstract screening, and full-text review, 26 articles were accepted for inclusion. The total mean follow-up duration was 32.0 ± 24.3 months. Reconstruction used microvascular free flaps in 65.5% (487/743), while 34.5% (256/743) were local flaps. 85.8% (307/358) of patients ambulated postoperatively. Revision surgery was required in 21% of patients during their respective follow-up periods. The limb salvage rate was 93.4% (958/1,026). Among pooled surgical outcomes, 22.2% (225/1,012) of patients experienced a perioperative complication. DISCUSSION: Our study demonstrates that although complication rates in lower extremity soft tissue sarcoma reconstruction may be further optimized, a multidisciplinary flap reconstructive approach provides high rates of limb salvage and functional postoperative ambulation.

Flap management following orthotopic heart transplantation: A single institution's review of 66 sternal wound complications.

BACKGROUND: Sternotomy wound complications are more frequent after orthotopic heart transplantation (OHT) compared to other cardiac surgeries, primarily due to additional risk factors, including immunosuppression. Flap closure often becomes necessary for definitive treatment, although there is a scarcity of data on the outcomes of sternal wound reconstruction in this specific population. METHODS: A retrospective analysis was conducted on 604 sternal wound reconstructions performed by a single surgeon between 1996 and 2023. Inclusion criteria comprised patients who underwent OHT as their primary cardiac procedure. Surgical interventions involved sternal hardware removal, debridement, and muscle flap closure. RESULTS: The study included 66 patients, with culture-positive wound infection being the most common indication for reconstruction (51.5%). The median duration between transplantation and sternal wound reconstruction was 25 days. Bilateral pectoralis major myocutaneous advancement flaps (n = 63), rectus abdominis flaps (n = 2), or pectoralis major turnover flaps (n = 1) were used. Intraoperative wound cultures revealed positivity in 48 patients (72.7%), with Staphylococcus epidermidis being the most frequently cultured organism (25.0%). The overall complication rate was 31.8%, and two patient deaths were related to sternal wounds, resulting from multiorgan failure following septic shock. The majority of the patients reported excellent long-term functional and esthetic outcomes. CONCLUSIONS: Sternal wounds following OHT pose a significant morbidity risk. Our strategy focuses on immediate and aggressive antibiotic therapy, thorough debridement, and definitive closure with bilateral pectoralis myocutaneous advancement flaps. This approach has demonstrated complication and mortality rates comparable to the general cardiac surgery population, as well as excellent functional and esthetic results.

Breast cancer-related lymphedema results in impaired epidermal differentiation and tight junction dysfunction.

Breast cancer-related lymphedema (BCRL) is characterized by skin changes, swelling, fibrosis, and recurrent skin infections. Clinical studies have suggested that lymphedema results in skin barrier defects; however, the underlying cellular mechanisms and the effects of bacterial contamination on skin barrier function remain unknown. In matched biopsies from patients with unilateral BCRL, we observed decreased expression of filaggrin and the tight junction protein zona occludens-1 (ZO-1) in skin affected by moderate lymphedema, or by subclinical lymphedema in which dermal backflow of lymph was identified by indocyanine green lymphography, relative to controls (areas without backflow and from the unaffected arm). In vitro stimulation of keratinocytes with lymph fluid obtained from patients undergoing lymphedema surgery led to the same changes, as well as increased expression of keratin 14, a marker of immature keratinocytes. Finally, using mouse models of lymphedema, we showed that like the clinical scenario, the expression of skin barrier proteins was decreased relative to normal skin and that colonization with S. epidermidis bacteria amplified this effect, as well as lymphedema severity. Taken together, our findings suggest that lymphatic fluid stasis contributes to skin barrier dysfunction in lymphedema.

Topical captopril: a promising treatment for secondary lymphedema.

Transforming growth factor-beta 1 (TGF-ß1)-mediated tissue fibrosis is an important regulator of lymphatic dysfunction in secondary lymphedema. However, TGF-ß1 targeting can cause toxicity and autoimmune complications, limiting clinical utility. Angiotensin II (Ang II) modulates intracellular TGF-ß1 signaling, and inhibition of Ang II production using angiotensin-converting enzyme (ACE) inhibitors, such as captopril, has antifibrotic efficacy in some pathological settings. Therefore, we analyzed the expression of ACE and Ang II in clinical lymphedema biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL) and mouse models, and found that cutaneous ACE expression is increased in lymphedematous tissues. Furthermore, topical captopril decreases fibrosis, activation of intracellular TGF-ß1 signaling pathways, inflammation, and swelling in mouse models of lymphedema. Captopril treatment also improves lymphatic function and immune cell trafficking by increasing collecting lymphatic pumping. Our results show that the renin-angiotensin system in the skin plays an important role in the regulation of fibrosis in lymphedema, and inhibition of this signaling pathway may hold merit for treating lymphedema.

The Future of Lymphedema: Potential Therapeutic Targets for Treatment.

Purpose of Review: This review aims to summarize the current knowledge regarding the pharmacological interventions studied in both experimental and clinical trials for secondary lymphedema. Recent Findings: Lymphedema is a progressive disease that results in tissue swelling, pain, and functional disability. The most common cause of secondary lymphedema in developed countries is an iatrogenic injury to the lymphatic system during cancer treatment. Despite its high incidence and severe sequelae, lymphedema is usually treated with palliative options such as compression and physical therapy. However, recent studies on the pathophysiology of lymphedema have explored pharmacological treatments in preclinical and early phase clinical trials. Summary: Many potential treatment options for lymphedema have been explored throughout the past two decades including systemic agents and topical approaches to decrease the potential toxicity of systemic treatment. Treatment strategies including lymphangiogenic factors, anti-inflammatory agents, and anti-fibrotic therapies may be used independently or in conjunction with surgical approaches.

Skin microbiome alterations in upper extremity secondary lymphedema.

Lymphedema is a chronic condition that commonly occur from lymphatic injury following surgical resection of solid malignancies. While many studies have centered on the molecular and immune pathways that perpetuate lymphatic dysfunction, the role of the skin microbiome in lymphedema development remains unclear. In this study, skin swabs collected from normal and lymphedema forearms of 30 patients with unilateral upper extremity lymphedema were analyzed by 16S ribosomal RNA sequencing. Statistical models for microbiome data were utilized to correlate clinical variables with microbial profiles. Overall, 872 bacterial taxa were identified. There were no significant differences in microbial alpha diversity of the colonizing bacteria between normal and lymphedema skin samples (p = 0.25). Notably, for patients without a history of infection, a one-fold change in relative limb volume was significantly associated with a 0.58-unit increase in Bray-Curtis microbial distance between paired limbs (95%CI = 0.11,1.05, p = 0.02). Additionally, several genera, including Propionibacterium and Streptococcus, demonstrated high variability between paired samples. In summary, we demonstrate high compositional heterogeneity in the skin microbiome in upper extremity secondary lymphedema, supporting future studies into the role of host-microbe interactions on lymphedema pathophysiology.

Dysregulation of Lymphatic Endothelial VEGFR3 Signaling in Disease.

Vascular endothelial growth factor (VEGF) receptor 3 (VEGFR3), a receptor tyrosine kinase encoded by the FLT4 gene, plays a significant role in the morphogenesis and maintenance of lymphatic vessels. Under both normal and pathologic conditions, VEGF-C and VEGF-D bind VEGFR3 on the surface of lymphatic endothelial cells (LECs) and induce lymphatic proliferation, migration, and survival by activating intracellular PI3K-Akt and MAPK-ERK signaling pathways. Impaired lymphatic function and VEGFR3 signaling has been linked with a myriad of commonly encountered clinical conditions. This review provides a brief overview of intracellular VEGFR3 signaling in LECs and explores examples of dysregulated VEGFR3 signaling in various disease states, including (1) lymphedema, (2) tumor growth and metastasis, (3) obesity and metabolic syndrome, (4) organ transplant rejection, and (5) autoimmune disorders. A more complete understanding of the molecular mechanisms underlying the lymphatic pathology of each disease will allow for the development of novel strategies to treat these chronic and often debilitating illnesses.

Pharmacological Treatment of Secondary Lymphedema.

Lymphedema is a chronic disease that results in swelling and decreased function due to abnormal lymphatic fluid clearance and chronic inflammation. In Western countries, lymphedema most commonly develops following an iatrogenic injury to the lymphatic system during cancer treatment. It is estimated that as many as 10 million patients suffer from lymphedema in the United States alone. Current treatments for lymphedema are palliative in nature, relying on compression garments and physical therapy to decrease interstitial fluid accumulation in the affected extremity. However, recent discoveries have increased the hopes of therapeutic interventions that may promote lymphatic regeneration and function. The purpose of this review is to summarize current experimental pharmacological strategies in the treatment of lymphedema.