The Pittsburgh Trunk Lymphedema Staging System (PTLSS) - a validated staging system for the description of breast cancer-associated trunk lymphedema.

BACKGROUND: Neither anatomic nor functional descriptions exist of trunk/breast lymphedema following breast cancer treatment. Indocyanine green (ICG)-lymphangiography has been shown to characterize lymph channel dysfunction seen in lymphedema. We propose using ICG-lymphangiography to evaluate trunk and breast lymphedema following breast cancer surgery to characterize the regions affected via a novel, validated staging system. METHODS: Patients undergoing revisional breast surgery with suspicion of upper extremity lymphedema between December 2014 and March 2020 were offered lymphangiography. The breast and lateral/anterior trunks were visualized and blindly evaluated using Koshima's patterns of dermal backflow. Patients were then staged. A linear-weighted Cohen's kappa statistic was calculated comparing each rated area and stage assignment. RESULTS: Fifty-two sides (29 patients) were included. Eight sides underwent no treatment and were considered controls. No lymphedema was identified within this cohort. One patient (two sides) had no transit of ICG. Seventy-six percent of the non-controls had dermal backflow. This was seen in 67% of anterior trunks, 50% of lateral trunks, 50% of inframammary folds (IMFs), 43% of inferior breasts, and 5% of superior breasts. Cohen's kappa for area agreement was 0.4117 ± 0.0535. Stage 0 was seen in 31 (±7)% of sides; stage 1: 21 (±1)%; stage 2: 22 (±5)%; stage 3: 18 (±4)%; stage 4: 5 (±1)%; and stage 5: 4 (±0). Cohen's kappa for staging was 0.8109 ± 0.0868. CONCLUSION: Following breast cancer surgery, lymphedema occurs throughout the trunk and breast. Severe dysfunction appears to be located around the inferior-lateral aspect of the breast and chest wall. Furthermore, the Pittsburgh Trunk Lymphedema Staging System is a validated measure of trunk and breast lymphedema.

Nipple Areola Complex Reconstruction With the "Half-Dome" Technique Following Implant-Based Breast Reconstruction.

BACKGROUND: No single technique for nipple areola reconstruction best fits every patient and clinical scenario. Many techniques fail to provide long-term projection. One especially challenging cohort are those patients who have undergone bilateral implant-based reconstruction. We developed a modification of the C-V flap reconstruction that increases projection in the bilateral, implant-based reconstruction patient. METHODS: All patients who underwent nipple areola reconstruction following implant-based breast reconstruction and who had at least a 12-month follow-up visit were identified. Nipple projection was measured and compared between the 2 groups. RESULTS: Forty patients were identified. Twelve patients, 23 nipples, underwent the standard C-V flap reconstruction. Twenty-eight patients, 59 nipples, underwent the half-dome modification. Average nipple projection following the half-dome technique is more than twice that of the C-V flap. CONCLUSIONS: The half-dome technique provides a useful alternative modification of the C-V flap in patients with implant-based reconstruction.

Utility and Cost Effectiveness of Routine, Histologic Evaluation of the Mastectomy Scar in Two-Stage, Implant-Based Reconstruction during Expander-to-Implant Exchange.

BACKGROUND: Routine histologic analysis of the mastectomy scar is well studied in the delayed breast construction population; no data regarding its utility in the immediate, staged reconstruction cohort have been published. METHODS: A retrospective review of all of the senior author's (C.D.C.) patients who underwent immediate, staged reconstruction was performed. The mastectomy scar was analyzed routinely at the time of expander-to-implant exchange. Six hundred forty-seven breasts were identified. The mastectomy scar, time between expander and permanent implant, average patient age, and mastectomy indication were calculated. A cost analysis was completed. RESULTS: All scar pathologic results were negative for in-scar recurrence. The majority, 353 breasts, underwent mastectomy for carcinoma, 94 for germline mutations, 15 for high-risk lesions, six for high family risk, and 179 for contralateral symmetry/risk reduction. The average age at mastectomy/expander placement was 47.7 ± 10.3 years, and the average time between expander placement and implant exchange was 254 ± 152 days. The total histologic charge per breast was $602. CONCLUSIONS: A clinically silent in-scar recurrence is, at most, a rare occurrence. Routine histologic analysis of the mastectomy scar can be safely avoided in the immediate, staged reconstruction cohort. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Pathways to Academic Leadership in Plastic Surgery: A Nationwide Survey of Program Directors, Division Chiefs, and Department Chairs of Plastic Surgery.

BACKGROUND: Many aspire to leadership in academic plastic surgery yet there is no well-documented pathway. METHODS: Information regarding plastic surgery residencies and program directors was obtained from the American Medical Association's FREIDA database. The division chief or department chair (academic head) of every academic plastic surgery program was identified. One Internet-based survey was distributed to academic heads; another, to program directors. RESULTS: Ninety academic heads were identified, 35 of whom also serve as program director. Sixty-seven unique program directors were identified. There was a 51 percent academic head response rate and a 65 percent program director response rate. Academic plastic surgery is overwhelmingly administered by midcareer men. The average program director was appointed at age 45 and has served for 7 years. She or he was trained through the independent track, completed additional training in hand surgery, and is a full professor. She or he publishes two or three peer-reviewed manuscripts per year and spends 9 hours per week in administration. The average academic head was appointed at age 45 and has held the position for 12 years. She or he was trained in the independent model, completed fellowship training, and is a full professor. She or he publishes five peer-reviewed manuscripts per year and spends 12 hours per week involved in administration. CONCLUSIONS: Program directors and academic heads serve nonoverlapping roles. Few program directors will advance to the role of academic head. Successful applicants to the program director position often serve as an associate program director and are seen as motivated resident educators. In contrast, those faculty members selected for the academic head role are academically accomplished administrators with business acumen.

The intestinal mucus layer is a critical component of the gut barrier that is damaged during acute pancreatitis.

Gut barrier failure has been implicated in the progression from single-organ injury to multiple-organ failure. The unstirred mucus layer is a major component of the physiological gut barrier; its role in acute pancreatitis (AP) is not clearly defined. Rats underwent biliopancreatic duct ligation-induced AP; two controls were used: biliopancreatic duct ligation with drainage and sham duct ligation. After 4.5 h, serum and ascitic amylase activity was measured. Mucus was analyzed for reactive nitrogen intermediate-mediated damage, reactive oxygen species-induced damage, and total antioxidant capacity. Mucus coverage and villous injury were assessed histologically. Ileum permeability was measured by diffusion of a fluorescent Dextran probe. Histology and morphology of the mucus layer were validated in a mouse AP model (intraductal taurocholate plus cerulein). Biliopancreatic duct ligation increased serum α-amylase, ascitic volume, and ascitic α-amylase. Intestinal permeability was increased, which was associated with loss of the unstirred mucus layer but not villous injury. These changes correlated with increased reactive oxygen species- and- reactive nitrogen intermediate-mediated mucus damage as well as decreased mucus total antioxidant capacity but were not present in the two control groups. Using a different model of AP in mice, the finding of mucus layer disruption was recapitulated at 6 h after AP, but by 24 h, rebound hypersecretion of inspissated mucus was seen. These results support the hypothesis that damage to the unstirred mucus layer with evidence of oxidative stress occurs during AP-induced gut barrier failure.

Intraluminal nonbacterial intestinal components control gut and lung injury after trauma hemorrhagic shock.

OBJECTIVE: To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma shock-induced gut and lung injury. BACKGROUND: Gut origin sepsis studies have highlighted the importance of the systemic component (ischemia-reperfusion) of gut injury, whereas the intraluminal component is less well studied. METHODS: In rats subjected to trauma hemorrhagic shock (T/HS) or sham shock, the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization whereas the role of the mucus layer was tested via the enteral administration of a mucus surrogate. In addition, the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically, and chemically. RESULTS: Pancreatic duct exteriorization abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented T/HS-induced gut and lung injury. Finally, pancreatic enzyme-induced gut and lung injury seems to involve mast cell activation because T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. CONCLUSIONS: These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.

Trauma-hemorrhagic shock induces a CD36-dependent RBC endothelial-adhesive phenotype.

OBJECTIVE: Microvascular dysfunction is a key element in the development of the multiple organ dysfunction syndrome. Although the mechanisms for this response are unclear, RBC adhesion to endothelium may initiate intravascular occlusion leading to ischemic tissue injury. Thus, we tested the hypothesis that trauma-hemorrhage induces RBC-endothelial cell adhesion. DESIGN: Prospective in vivo and in vitro animal study and analysis of patient blood samples. SETTING: University research laboratory and hospital emergency and trauma units. INTERVENTION: We initially assayed RBC adhesion to endothelial cells in vitro using RBCs obtained from rats subjected to trauma-hemorrhagic shock or sham shock as well as from severely injured trauma patients. Subsequently, we measured the role of putative RBCs and endothelial cell receptors in the increased RBC-endothelial cell adhesive response. MAIN RESULTS: In both rats and humans, trauma-hemorrhagic shock increased RBC adhesion to endothelium as well as increasing several putative RBC surface adhesion molecules including CD36. The critical factor leading to RBC-endothelial cell adhesion was increased surface RBC CD36 expression. Adhesion of trauma-hemorrhagic shock RBCs was mediated, at least in part, by the binding of RBC CD36 to its cognate endothelial receptors (αVß3 and VCAM-1). Gut-derived factors carried in the intestinal lymphatics triggered these trauma-hemorrhagic shock-induced RBC changes because 1) preventing trauma-hemorrhagic shock intestinal lymph from reaching the systemic circulation abrogated the RBC effects, 2) in vitro incubation of naïve whole blood with trauma-hemorrhagic shock lymph replicated the in vivo trauma-hemorrhagic shock-induced RBC changes while 3) injection of trauma-hemorrhagic shock lymph into naïve animals recreated the RBC changes observed after actual trauma-hemorrhagic shock. CONCLUSIONS: 1) Trauma-hemorrhagic shock induces rapid RBC adhesion to endothelial cells in patients and animals. 2) Increased RBC CD36 expression characterizes the RBC-adhesive phenotype. 3) The RBC phenotypic and functional changes were induced by gut-derived humoral factors. These novel findings may explain the microvascular dysfunction occurring after trauma-hemorrhagic shock, sepsis, and other stress states.

Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.

Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radical-mediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS- and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.

Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and hemorrhagic shock.

We tested if vagus nerve stimulation (VNS) would prevent gut injury, mesenteric lymph toxicity, and systemic multiple organ dysfunction syndrome following trauma-hemorrhagic shock (T/HS). Four groups of experiments were performed. The first tested whether VNS (5 V for 10 min) would protect against T/HS-induced increases in gut and lung permeability as well as neutrophil priming. In the second experiment, mesenteric lymph was collected from rats subjected to T/HS or trauma-sham shock with or without VNS and then injected into naive mice to assess its biologic activity. Lung permeability, neutrophil priming, and red blood cell deformability were measured. Next, the role of the spleen in VNS-mediated protection was tested by measuring gut and lung injury in splenectomized rats subjected to sham or actual VNS. Lastly, the ability of nicotine to replicate the gut-protective effect of VNS was tested. Vagus nerve stimulation protected against T/HS-induced gut injury, lung injury, and neutrophil priming (P < 0.05). Not only did VNS limit organ injury after T/HS, but in contrast to the mesenteric lymph collected from the sham-VNS T/HS rats, the mesenteric lymph from the VNS T/HS rats did not cause lung injury, neutrophil priming, or loss of red blood cell deformability (P < 0.05) when injected into naive mice. Removal of the spleen did not prevent the protective effects of VNS on gut or lung injury after T/HS. Similar to VNS, the administration of nicotine also protected the gut from injury after T/HS. Vagus nerve stimulation prevents T/HS-induced gut injury, lung injury, neutrophil priming, and the production of biologically active mesenteric lymph. This protective effect of VNS was not dependent on the spleen but appeared to involve a cholinergic nicotinic receptor, because its beneficial effects could be replicated with nicotine.

Vagal nerve stimulation modulates gut injury and lung permeability in trauma-hemorrhagic shock.

BACKGROUND: Hemorrhagic shock is known to disrupt the gut barrier leading to end-organ dysfunction. The vagus nerve can inhibit detrimental immune responses that contribute to organ damage in hemorrhagic shock. Therefore, we explored whether stimulation of the vagus nerve can protect the gut and recover lung permeability in trauma-hemorrhagic shock (THS). METHODS: Male Sprague-Dawley rats were subjected to left cervical vagus nerve stimulation at 5 V for 10 minutes. The right internal jugular and femoral artery were cannulated for blood withdrawal and blood pressure monitoring, respectively. Animals were then subjected to hemorrhagic shock to a mean arterial pressure between 30 mm Hg and 35 mm Hg for 90 minutes then reperfused with their own whole blood. After observation for 3 hours, gut permeability was assessed with fluorescein dextran 4 in vivo injections in a ligated portion of distal ileum followed by Evans blue dye injection to assess lung permeability. Pulmonary myeloperoxidase levels were measured and compared. RESULTS: Vagal nerve stimulation abrogated THS-induced lung injury (mean [SD], 8.46 [0.36] vs. 4.87 [0.78]; p < 0.05) and neutrophil sequestration (19.39 [1.01] vs. 12.83 [1.16]; p < 0.05). Likewise, THS gut permeability was reduced to sham levels. CONCLUSION: Neuromodulation decreases injury in the THS model as evidenced by decreased gut permeability as well as decreased lung permeability and pulmonary neutrophil sequestration in a rat model.