Topical therapy for regression and melanoma prevention of congenital giant nevi.

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate immunity that ablated detectable nevocytes, fully prevented melanoma, and regressed human giant nevus xenografts. These findings reveal nevus mechanistic vulnerabilities and suggest opportunities for topical interventions that may alter the therapeutic options for children with congenital giant nevi.

Prospective Sensory Outcomes for Targeted Nipple Areola Complex Reinnervation (TNR) in Gender-Affirming Double Incision Mastectomy with Free Nipple Grafting.

OBJECTIVE: This study analyses the anatomy and sensory outcomes of targeted nipple areola complex reinnervation (TNR) in gender-affirming double incision mastectomy with free nipple grafting (FNG). BACKGROUND: TNR is a novel technique to preserve and reconstruct intercostal nerves (ICN) to improve postoperative sensation. There is little evidence on relevant anatomy and outcomes. METHODS: 25 patients were prospectively enrolled. Data included demographics, surgical technique, and axon/fascicle counts. Quantitative sensory evaluation using monofilaments and qualitative patient reported questionnaires were completed preoperatively, and at one, three, six, nine and twelve months postoperatively. RESULTS: 50 mastectomies were performed. Per mastectomy, the median number of ICN found and used was 2 (1-5). Axon and fascicle counts were not significantly different between ICN branches ( P >0.05). BMI ≥30 kg/m 2 and mastectomy weight ≥800 g were associated with significantly worse preoperative sensation ( P <0.05). Compared to preoperative values, NAC sensation was worse at 1 month ( P <0.01), comparable at 3 months ( P >0.05), and significantly better at 12 months ( P <0.05) postoperatively. Chest sensation was comparable to the preoperative measurements at 1 and 3 months ( P >0.05), and significantly better at 12 months ( P <0.05) postoperatively. NAC sensation was significantly better when direct coaptation was performed compared to use of allograft only ( P <0.05), and with direct coaptation of ≥2 branches compared to direct coaptation of a single branch ( P <0.05). All patients reported return of nipple and chest sensation at one year postoperatively and 88% reported return of some degree of erogenous sensation. CONCLUSION: TNR allows for restoration of NAC and chest sensation within 3 months postoperatively. Use of multiple ICN branches and direct coaptation led to the best sensory outcomes.

Readability analysis and concept mapping of PROMs used for headache disorders.

OBJECTIVE: To assess the readability and the comprehensiveness of patient-reported outcome measures (PROMs) utilized in primary headache disorders literature. BACKGROUND: As the health-care landscape has evolved toward a patient-centric model, numerous PROMs have been developed to capture treatment outcomes in patients with headache disorders. For these PROMs to advance our understanding of headache disorders and their treatment impact, they must be easy to understand (i.e., reading grade level 6 or less) and comprehensively capture what matters to patients with headache. The aim of this study was to (a) assess the readability of PROMs utilized in headache disorders literature, and (b) assess the comprehensiveness of PROMs by mapping their content to a health-related quality of life framework. METHODS: In this scoping review, recently published systematic reviews were used to identify PROMs used in primary headache disorders literature. Readability analysis was performed at the level of individual items and full PROM using established readability metrics. The content of the PROMs was mapped against a health-related quality-of-life framework by two independent reviewers. RESULTS: In total, 22 PROMs (15 headache disorders related, 7 generic) were included. The median reading grade level varied between 7.1 (interquartile range [IQR] 6.3-7.8) and 12.7 (IQR 11.8-13.2). None of the PROMs were below the recommended reading grade level for patient-facing material (grade 6). Three PROMs, the Migraine-Treatment Assessment Questionnaire, the Eurolight, and the European Quality of Life 5 Dimensions 3 Level Version, were between reading grade levels 7 and 8; the remaining 19 PROMs were above reading grade level 8. In total, the PROMs included 425 items. Most items (n = 134, 32%) assessed physical function (e.g., work, activities of daily living). The remaining items assessed physical symptoms (n = 127, 30%; e.g., pain, nausea), treatment effects on symptoms (n = 65, 15%; e.g., accompanying symptoms relief, headache relief), treatment impact (n = 56, 13%; e.g., function, side effects), psychological well-being (n = 41, 10%; e.g., anger, frustration), social well-being (n = 29, 7%; e.g., missing out on social activities, relationships), psychological impact (n = 14, 3%; e.g., feeling [not] in control, feeling like a burden), and sexual well-being (n = 3, 1%; e.g., sexual activity, sexual interest). Some of the items pertained to treatment (n = 27, 6%), of which most were about treatment type and use (n = 12, 3%; e.g., medication, botulinum toxin), treatment access (n = 10, 2%; e.g., health-care utilization, cost of medication), and treatment experience (n = 9, 2%; e.g., treatment satisfaction, confidence in treatment). CONCLUSION: The PROMs used in studies of headache disorders may be challenging for some patients to understand, leading to inaccurate or missing data. Furthermore, no available PROM comprehensively measures the health-related quality-of-life impact of headache disorders or their treatment, resulting in a limited understanding of patient-reported outcomes. The development of an easy-to-understand, comprehensive, and validated headache disorders-specific PROM is warranted.

Surgical Management of Headache Disorders - A Systematic Review of the Literature.

PURPOSE OF REVIEW: This review article critically evaluates the latest advances in the surgical treatment of headache disorders. RECENT FINDINGS: Studies have demonstrated the effectiveness of innovative screening tools, such as doppler ultrasound, pain drawings, magnetic resonance neurography, and nerve blocks to help identify candidates for surgery. Machine learning has emerged as a powerful tool to predict surgical outcomes. In addition, advances in surgical techniques, including minimally invasive incisions, fat injections, and novel strategies to treat injured nerves (neuromas) have demonstrated promising results. Lastly, improved patient-reported outcome measures are evolving to provide a framework for comparison of conservative and invasive treatment outcomes. Despite these developments, challenges persist, particularly related to appropriate patient selection, insurance coverage, delays in diagnosis and surgical treatment, and the absence of standardized measures to assess and compare treatment impact. Collaboration between medical/procedural and surgical specialties is required to overcome these obstacles.

Micro-Coring: A Novel Approach to Perioral Rejuvenation.

BACKGROUND: A long philtrum and poor perioral skin quality are stigmata of the aging face. Micro-coring is a novel technology that allows for scarless skin removal. OBJECTIVES: This study aimed to determine if micro-coring can shorten the philtrum and improve perioral skin quality. METHODS: A retrospective cohort study was performed on subjects who underwent facelift with perioral micro-coring and age/BMI-matched control patients who underwent facelift alone. Preoperative and postoperative three-dimensional facial imaging was performed. Standard perioral distances and percent change were calculated. Perioral skin quality was evaluated by blinded raters using the Scientific Assessment Scale of Skin Quality (SASSQ) and Global Aesthetic Improvement Scale (GAIS). RESULTS: Thirteen subjects and thirteen controls were included with a mean follow-up of 8.9 months (range 3.0-21.5). Subjects had significantly shorter mean philtral length postoperatively as compared to preoperatively, with an average decrease of 6.18% (±2.25%) (p<0.05). Controls did not experience significant changes in philtrum length (p>0.05). Postoperative philtrum length was significantly shorter in subjects as compared to controls (p<0.05). There were no significant changes in other perioral measurements. Perioral skin elasticity and wrinkles significantly improved in subjects as compared to controls and subjects had significantly greater GAIS scores (p<0.05). CONCLUSIONS: Micro-coring can achieve perioral rejuvenation through measurable shortening of the philtrum and observable improvement in skin quality. Non-surgical techniques continue to find new ways to achieve aesthetic goals without significant recovery or scarring and offer value to patients and clinicians.

OnabotulinumtoxinA alters inflammatory gene expression and immune cells in chronic headache patients.

Occipital headache, the perception of pain in the back of the head, is commonly described by patients diagnosed with migraine, tension-type headache, and occipital neuralgia. The greater and lesser occipital nerves play central role in the pathophysiology of occipital headache. In the clinical setup, such headaches are often treated with onabotulinumtoxinA, a neurotoxin capable of disrupting ability of nociceptors to get activated and/or release proinflammatory neuropeptides. Attempting to understand better onabotulinumtoxinA mechanism of action in reducing headache frequency, we sought to determine its effects on expression of inflammatory genes in injected occipital tissues. To achieve this goal, we injected 40 units of onabotulinumtoxinA into four muscle groups (occipitalis, splenius capitis, semispinalis capitis, and trapezius muscles-all located on one side of the occiput) of patients with chronic bilateral occipital headache scheduled for occipital nerve decompression surgery 1 month later. At the time of surgery, we collected discarded muscle, fascia and periosteum tissues from respective locations on both sides of the neck and occiput and performed targeted transcriptome analyses to determine expression level of inflammatory genes in onabotulinumtoxinA-injected and onabotulinumA-uninjected tissues. We found that (i) onabotulinumtoxinA alters expression of inflammatory genes largely in periosteum, minimally in muscle and not at all in fascia; (ii) expression of inflammatory genes in uninjected periosteum and muscle is significantly higher in historical onabotulinumA responders than historical non-responders; (iii) in historical responders' periosteum, onabotulinumA decreases expression of nearly all significantly altered genes, gene sets that define well recognized inflammatory pathways (e.g. pathways involved in adaptive/innate immune response, lymphocyte activation, and cytokine, chemokine, NF-kB, TNF and interferon signalling), and abundance of 12 different immune cell classes (e.g. neutrophils, macrophages, cytotoxic T-, NK-, Th1-, B- and dendritic-cells), whereas in historical non-responders it increases gene expression but to a level that is nearly identical to the level observed in the uninjected periosteum and muscle of historical responders; and surprisingly (iv) that the anti-inflammatory effects of onabotulinumA are far less apparent in muscles and absent in fascia. These findings suggest that in historical responders' periosteum-but not muscle or fascia-inflammation contributes to the pathophysiology of occipital headache, and that further consideration should be given to the possibility that onabotulinumA mechanism of action in migraine prevention could also be achieved through its ability to reduce pre-existing inflammation, likely through localized interaction that lead to reduction in abundance of immune cells in the calvarial periosteum.

Treatment Delay From Onset of Occipital Neuralgia Symptoms to Treatment with Nerve Decompression Surgery: A Prospective Cohort Study.

BACKGROUND: The aim of this study was to a) evaluate the time between onset of occipital neuralgia symptoms and nerve decompression surgery, b) perform a cost comparison analysis between surgical and non-surgical treatment of occipital neuralgia and c) report postoperative results of nerve decompression for occipital neuralgia. METHODS: 1,112 subjects who underwent screening for nerve decompression surgery were evaluated for occipital neuralgia. 367 (33%) patients met the inclusion criteria. Timing of occipital neuralgia symptom onset and pain characteristics were prospectively collected. Cost associated with the non-surgical treatment of occipital neuralgia was calculated for the period between onset of symptoms and surgery. RESULTS: 226 (73%) patients underwent occipital nerve decompression. The average time between onset of occipital neuralgia and surgery was 19 years (7.1-32). Postoperatively, the median number of pain days per month decreased by 17 (0-26, 57%) (p < 0.001), the median pain intensity decreased by 4 (2-8, 44%) (p < 0.001), and median pain duration in hours was reduced by 12 (2-23, 50%) (p < 0.001). The annual mean cost of non-surgical occipital neuralgia treatment was $28,728.82 ($16,419.42-$41,198.41) per patient. The mean cost during the 19-year timeframe prior to surgery was $545,847.75($311,968.90-$782,769.82). CONCLUSION: This study demonstrates that patients suffer from occipital neuralgia for an average of 19 years prior to undergoing surgery. Nerve decompression reduces symptom severity significantly and should be considered earlier in the treatment course of occipital neuralgia that is refractory to conservative treatment to prevent patient morbidity and decrease direct and indirect healthcare costs. IRB REGISTRATION NUMBER & NAME: Weill Cornell Medicine: 23-04025985, Prospective Cohort Study Investigating Long- Term Outcomes After Headache Surgery.The Massachusetts General Hospital: 2012P001527, Correlation of pre-operative pain self-efficacy and post-operative migraine-specific symptoms and disability.

Pedicled vastus lateralis myocutaneous flap for sacropelvic defects after wide oncologic resection: Wound complications and outcomes.

BACKGROUND AND OBJECTIVES: Adequate coverage of the soft tissue defects from wide resection of sacropelvic malignancies remains challenging. The vastus lateralis flap has been described for coverage in the setting of trauma and infection. This flap has not been described for coverage of sacropelvic tumor defects. METHODS: This is a retrospective cohort study of adult patients who underwent wide resection of a primary sacropelvic malignancy with reconstruction employing a pedicled vastus lateralis flap at two tertiary care centers. Patient demographics, tumor staging, and rate of complications were assessed. RESULTS: Twenty-eight patients were included, with a median age of 51 years. The most common primary tumor was chondrosarcoma followed by chondroblastic osteosarcoma. The median follow-up was 1.1 years. There were 10 cases of wound infection requiring re-operation and three cases of flap failure. CONCLUSIONS: We describe a pedicled vastus lateralis flap for coverage of defects after wide resection of sacropelvic malignancies. A large proportion of our cohort had independent risk factors for wound complications. Even with a cohort with high baseline risk for wound complications, we show that the use of a pedicled vastus lateralis flap is a safe reconstructive option with a wound complication rate in line with the literature.

Postmastectomy Radiation Therapy on Permanent Implants or Tissue Expanders: Which is Better?

OBJECTIVES: This study evaluates complications and reconstructive failure rates in implant-based reconstruction with radiotherapy. BACKGROUND: Postmastectomy radiotherapy may adversely affect breast reconstructive outcomes. However, the comparative effect of radiotherapy on direct-to-implant versus tissue expander-implant reconstruction has not been examined. METHODS: Single institution retrospective review was performed and patients were followed 2 to 10 years. RESULTS: Of 1566 patients, 265 patients received radiation (149 immediate implants and 116 tissue expanders). Demographics were similar except more smokers in the expander group (7.7% vs 1.3%; P = 0.012). Patients who received radiation with an expander in place had overall more complications (32.8% vs 11.4%; P < 0.001), skin necrosis (10.3% vs 4.0%; P = 0.043), wound breakdown (9.5% vs 2.7%; P = 0.029), and infections (16.4% vs 4.03%; P = 0.001) leading to a higher rate of explantation (16.4% vs 4.0%; P < 0.001). A radiation boost likewise predicted complications [odds ratio (OR) 2.199, 95% confidence interval (CI) 1.154-4.188, P = 0.017]. When comparing reconstructive outcomes, radiated expanders had a higher failure rate (21.6% vs 11.4%; P = 0.025). Revision for capsular contracture was similar between the 2 cohorts (11.4% vs 11.2%; P = 0.959) as were revision rates for contour asymmetry and breast asymmetry. In our multivariable logistic regression analysis, radiation to the expander had a higher risk of reconstruction failure than radiation to the permanent implant (OR 2.020, 95% CI 1.010-4.037, P = 0.047). CONCLUSION: Most patients had successful implant-based reconstructions after mastectomy and radiotherapy. Our study showed radiotherapy after direct-to-implant breast reconstruction had a lower rate of complications and reconstructive failure compared to tissue expander-implant reconstruction.

Evaluating and Comparing Emotional Intelligence and Improvement Mindset of Plastic Surgery Residents.

BACKGROUND: Emotional Intelligence (EI) has been linked to burnout, job satisfaction, and work performance among resident physicians. Individuals with a growth mindset believe intelligence and ability are traits that can be increased or improved upon through learning. EI and mindset have yet to be studied among plastic surgeons in the United States. MATERIALS AND METHODS: An online survey was distributed to plastic surgery residents and general surgery residents at a single institution containing a validated EI survey tool (TEIQue-SF). Second, a survey was sent to all plastic surgery residents in the United States containing the TEIQue-SF and a validated survey tool to assess mindset (ITIS). RESULTS: The response rate for the local study was 82% (plastic surgery) and 75% (general surgery). Only 7.8% of plastic surgery residents had any prior formal EI training or education. Mean global EI scores of local plastic surgery residents were higher than the normative population sample (P <0.0001). Plastic surgery and general surgery residents had similar EI scores. Integrated residents and junior plastic surgery residents had higher Well-Being scores compared to independent (P = 0.04) and senior residents (P = 0.04). Sixty-four plastic surgery residents completed the national survey. No correlation was found between EI and ITIS scores among the national plastic surgery resident cohort. CONCLUSION: Despite different work profiles, general surgery and plastic surgery residents may have similar EI profiles. Mindset does not appear to correlate to EI domains. Future studies will focus on how EI and mindset may develop over the course of residency training and their relationship to overall resident wellness.

Photochemical Tissue Passivation of Arteriovenous Grafts Prevents Long-Term Development of Intimal Hyperplasia in a Swine Model.

BACKGROUND: The autologous vein remains the standard conduit for lower extremity and coronary artery bypass grafting despite a 30%-50% 5-y failure rate, primarily attributable to intimal hyperplasia (IH) that develops in the midterm period (3-24 mo) of graft maturation. Our group discovered that externally strengthening vein grafts by cross-linking the adventitial collagen with photochemical tissue passivation (PTP) mitigates IH in an arteriovenous model at 4 wk. We now investigate whether this effect is retained in the midterm period follow-up. METHODS: Six Hanford miniature pigs received bilateral carotid artery interposition vein grafts. In each animal, the external surface of one graft was treated with PTP before grafting, whereas the opposite side served as the untreated control. The grafts were harvested after 3 mo. Ultrasound evaluation of all vein grafts was performed at the time of grafting and harvest. The grafts were also evaluated histomorphometrically and immunohistologically for markers of IH. RESULTS: All vein grafts were patent at 3 mo except one graft in the PTP-treated group because of early technical failure. The control vein grafts had significantly greater IH than PTP-treated grafts at 3 mo, as evidenced by the intimal area (2.6 ± 1.0 mm2versus 1.4 ± 1.5 mm2, respectively, P = 0.045) and medial area (5.1 ± 1.9 mm2versus 2.7 ± 2.4 mm2, respectively, P = 0.048). The control grafts had an increased presence and proliferation of mural myofibroblasts with greater smooth muscle actin and proliferating cell nuclear antigen staining. CONCLUSIONS: PTP treatment to the external surface of the vein grafts decreases IH at 3 mo after arteriovenous grafting and may prevent future graft failure.

Migraine Surgery: An All or Nothing Phenomenon? Prospective Evaluation of Surgical Outcomes.

OBJECTIVE: A detailed analysis of outcomes after migraine surgery suggests an anatomic etiology of pain, such as peripheral nerve compression, in select patients. BACKGROUND: Historically, surgeons have not played a role in the treatment of migraine. However, a subgroup of patients with extracranial anatomic triggers appear to benefit from surgical intervention. Traditionally, the determination of success or failure of migraine surgery is based on whether there is greater or less than 50% improvement of the migraine headache index (MHI) after surgery. However, in this study, patients either did not respond to treatment (≤5%) or improved completely (≥80%). Detailed analysis is provided of this surprising finding. METHODS: Subjects completed a prospective migraine questionnaire preoperatively as well as at 3 and 12 months postoperatively. RESULTS: All variables improved significantly from baseline. Interestingly, in 83% of patients, the MHI improved either ≥80% or ≤5%, suggesting a more binary distribution. Only 17% of indices fell in the intermediate (5% to 80%) range. Moreover, 69% of patients had ≥80% improvement resulting in a mean improvement of 96% in this group. The remaining 14% had ≤5% improvement, with an average improvement of 0%. CONCLUSION: Migraine surgery remains controversial. Traditional conservative therapy targets the central theory of migraine propagation. This study again prospectively demonstrates the efficacy of surgical trigger site deactivation in migraine patients. Patients either failed to improve or improved after surgery, with few intermediate outcomes. The binary distribution of data lends further support to an anatomic etiology of pain, that is, peripheral nerve compression, in select patients.

Photochemical Tissue Passivation Prevents Contracture of Full Thickness Wounds in Mice.

BACKGROUND AND OBJECTIVES: Wound contracture formation from excessive myofibroblast activity can result in debilitating morbidities. There are currently no treatments to prevent contracture. Photochemical tissue passivation (PTP), an established, safe, and user-friendly treatment modality, crosslinks collagen by a light-activated process, thus modulating the wound healing response and scarring. We hypothesised that PTP treatment would reinforce wounds by blunting the fibrotic response thus limiting contracture. STUDY DESIGN/MATERIALS AND METHODS: Full-thickness, 1 cm × 1 cm excisional wounds were created on the dorsum of 32 C57BL/6 mice. Treated wounds were painted with photosensitizing dye and exposed to visible light. Wounds were serially photographed over 6 weeks to measure wound contracture. At 7, 14, 21, and 42 days after wound creation, mice were euthanized and wounds were harvested for histologic review by a dermatopathologist. RESULTS: By Day 7, control wounds had significantly more contracture than those treated with PTP (33.0 ± 17.1% and 19.3 ± 9.0%, respectively; P = 0.011). PTP-treated wounds maintained approximately 20% less contracture than controls from Day 14 and on (P < 0.05). By Day 42, wounds had contracted by 86.9 ± 5.5% in controls and 64.2 ± 3.2% in PTP-treated wounds (P < 0.03). Histologically, PTP wounds had earlier growth and development of dermal collagen, neovascularization, and development of skin appendages, compared with control wounds. CONCLUSIONS: PTP significantly limits contracture of full-thickness wounds and improves wound healing. PTP-treated wounds histologically demonstrate more mature structural organization than untreated wounds and closely resemble native skin. PTP treatment may be applicable not only for excisional wounds, but also for wounds with a high incidence of contracture and associated morbidity. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Photochemical Tissue Passivation Attenuates AV Fistula Intimal Hyperplasia.

OBJECTIVE: We hypothesized that decreasing vein compliance would protect the vein against stretch injury and reduce intimal hyperplasia (IH). BACKGROUND: Although arteriovenous fistulas (AVFs) are the criterion standard for vascular access, their effectiveness is limited by poor patency with 40% to 60% failing due to IH. Venous stretch injury from exposure to arterial pressure induces IH. Photochemical tissue passivation (PTP) crosslinks adventitial collagen, decreasing vein compliance to resemble that of an artery. METHODS: AVFs were created between the femoral artery and epigastric vein in rats (n = 29). PTP was performed on the vein immediately before vessel anastomosis. AVFs were harvested after four weeks. Venous diameter was measured at the initial procedure and harvest. Intimal area was measured for each segment. Ultrasound was performed at harvest to measure AVF flow. RESULTS: Following AVF construction, venous diameter increased by 10% ±â€Š18% for PTP-treated vessels and 78% ±â€Š27% for controls (P ≤ 0.0001). At one month, PTP reduced AVF dilation by 71% compared to control (69% ±â€Š29% vs 241% ±â€Š78%; P ≤ 0.0001). Both juxta-anastomotic intimal area and total intimal area were reduced in PTP-treated vessels compared to control vessels. Specifically, intimal area was 0.024 ±â€Š0.018 and 0.095 ±â€Š0.089 mm for PTP-treated juxta-anastomotic segments of AVF and control, respectively (P < 0.05). Mean total intimal area for PTP-treated and control AVF were 0.080 ±â€Š0.042 and 0.190 ±â€Š0.110 mm, respectively (P < 0.03). AVF flow was 46.9 ±â€Š35.3 and 19.1 ±â€Š10.1 mL/min for PTP-treated and control AVF, respectively (P < 0.109). CONCLUSIONS: These data demonstrate that PTP represents a promising therapy for the prevention of AVF IH, a process that might improve surgical outcomes for patients receiving hemodialysis.

Penis Transplantation: First US Experience.

OBJECTIVE: We describe the first successful penis transplant in the United States in a patient with a history of subtotal penectomy for penile cancer. BACKGROUND: Penis transplantation represents a new paradigm in restoring anatomic appearance, urine conduit, and sexual function after genitourinary tissue loss. To date, only 2 penis transplants have been performed worldwide. METHODS: After institutional review board approval, extensive medical, surgical, and radiological evaluations of the patient were performed. His candidacy was reviewed by a multidisciplinary team of surgeons, physicians, psychiatrists, social workers, and nurse coordinators. After appropriate donor identification and recipient induction with antithymocyte globulin, allograft procurement and recipient preparation took place concurrently. Anastomoses of the urethra, corpora, cavernosal and dorsal arteries, dorsal vein, and dorsal nerves were performed, and also inclusion of a donor skin pedicle as the composite allograft. Maintenance immunosuppression consisted of mycophenolate mofetil, tacrolimus, and methylprednisolone. RESULTS: Intraoperative, the allograft had excellent capillary refill and strong Doppler signals after revascularization. Operative reinterventions on postoperative days (PODs) 2 and 13 were required for hematoma evacuation and skin eschar debridement. At 3 weeks, no anastomotic leaks were detected on urethrogram, and the catheter was removed. Steroid resistant-rejection developed on POD 28 (Banff I), progressed by POD 32 (Banff III), and required a repeat course of methylprednisolone and antithymocyte globulin. At 7 months, the patient has recovered partial sensation of the penile shaft and has spontaneous penile tumescence. Our patient reports increased overall health satisfaction, dramatic improvement of self-image, and optimism for the future. CONCLUSIONS: We have shown that it is feasible to perform penile transplantation with excellent results. Furthermore, this experience demonstrates that penile transplantation can be successfully performed with conventional immunosuppression. We propose that our successful penile transplantation pilot experience represents a proof of concept for an evolution in reconstructive transplantation.

A Personal Approach to Bilateral Cleft Lip Repair.

Dr Michael B. Lewis has been using his personal approach to bilateral cleft lip (BCL) repair for 30 years to achieve a loose, pouting upper lip, a 90-degree columellar-labial angle, and a projecting nasal tip. This article describes technique and results.

Prevention of vein graft intimal hyperplasia with photochemical tissue passivation.

OBJECTIVE: Saphenous vein is the conduit of choice for bypass grafting. Saphenous vein grafts have poor long-term patency rates because of intimal hyperplasia (IH) and subsequent accelerated atherosclerosis. One of the primary triggers of IH is endothelial injury resulting from excessive dilation of the vein after exposure to arterial pressures. Photochemical tissue passivation (PTP) is a technology that cross-links adventitial collagen by a light-activated process, which limits dilation by improving vessel compliance. The objective of this study was to investigate whether PTP limits the development of IH in a rodent venous interposition graft model. METHODS: PTP is accomplished by coating venous adventitia with a photosensitizing dye and exposing it to light. To assess the degree of collagen cross-linking after PTP treatment, a biodegradation assay was performed. Venous interposition grafts were placed in the femoral artery of Sprague-Dawley rats. Rats were euthanized after 4 weeks, and intimal thickness was measured histologically. Vein dilation at the time of the initial procedure was also measured. RESULTS: Time to digestion was 63 ± 7 minutes for controls, 101 ± 2.4 minutes for rose bengal (RB), and 300 ± 0 minutes for PTP (P < .001 PTP vs control). A total of 37 animals underwent the procedure: 12 PTP, 12 RB only, and 13 untreated controls. Dilation of the graft after clamp release was 99% for control, 65% for RB only, and 19% for PTP-treated (P < .001 PTP vs control). Intimal thickness was 77 ± 59 µm in controls, 60 ± 27 µm in RB only, and 33 ± 28 µm in PTP-treated grafts. There was a statistically significant 57% reduction in intimal thickness after treatment with PTP compared with untreated controls (P = .03). CONCLUSIONS: PTP treatment of venous interposition grafts in a rat model resulted in significant collagen cross-linking, decreased vessel compliance, and significant reduction in IH.

Occult Histopathology and Its Predictors in Contralateral and Bilateral Prophylactic Mastectomies.

BACKGROUND: The last decade has seen an increasing prevalence of prophylactic mastectomies with decreasing age of patients treated for breast cancer. Data are limited on the prevalence of histopathologic abnormalities in this population. This study aimed to measure the prevalence of histopathologic findings in contralateral prophylactic mastectomy (CPM) and bilateral prophylactic mastectomy (BPM) patients and identify predictors of findings. METHODS: Our institution's prophylactic mastectomies from 2004 to 2011 were reviewed. Breast specimens with prior malignancies were excluded. Patient factors and pathology reports were collected. Independent predictive factors were identified with univariate and multivariate logistic analysis. RESULTS: A total of 524 specimens in 454 patients were identified. Malignancy was found in 7.0% of CPM and 5.7% of BPM specimens. In CPM patients, ipsilateral lobular carcinoma-in situ [odds ratio (OR) 4.0] and mammogram risk group (OR 2.0) were predictive of malignancy. Age group (OR 1.5), ipsilateral lobular carcinoma-in situ (OR 2.3), and prior bilateral salpingo-oophorectomy (OR 0.3) were predictive of moderate- to high-risk histopathology. Only increasing age group was predictive of increased moderate- to high-risk histopathology in BPM patients (OR 2.3). There were no independent predictors of malignancy in BPM. BRCA status was not predictive in either CPM or BPM. CONCLUSIONS: Patients with lobular carcinoma-in situ in the index breast or high-risk mammograms have a higher prevalence of malignancies. Although BRCA patients may benefit from prophylactic mastectomy, the genetic diagnosis does not increase the prevalence of detecting occult pathology. BPM patients can be counseled about relative risk, where occult pathology increases with age.

Eradication of multidrug-resistant pseudomonas biofilm with pulsed electric fields.

Biofilm formation is a significant problem, accounting for over eighty percent of microbial infections in the body. Biofilm eradication is problematic due to increased resistance to antibiotics and antimicrobials as compared to planktonic cells. The purpose of this study was to investigate the effect of Pulsed Electric Fields (PEF) on biofilm-infected mesh. Prolene mesh was infected with bioluminescent Pseudomonas aeruginosa and treated with PEF using a concentric electrode system to derive, in a single experiment, the critical electric field strength needed to kill bacteria. The effect of the electric field strength and the number of pulses (with a fixed pulse length duration and frequency) on bacterial eradication was investigated. For all experiments, biofilm formation and disruption were confirmed with bioluminescent imaging and Scanning Electron Microscopy (SEM). Computation and statistical methods were used to analyze treatment efficiency and to compare it to existing theoretical models. In all experiments 1500 V are applied through a central electrode, with pulse duration of 50 µs, and pulse delivery frequency of 2 Hz. We found that the critical electric field strength (Ecr) needed to eradicate 100-80% of bacteria in the treated area was 121 ± 14 V/mm when 300 pulses were applied, and 235 ± 6.1 V/mm when 150 pulses were applied. The area at which 100-80% of bacteria were eradicated was 50.5 ± 9.9 mm(2) for 300 pulses, and 13.4 ± 0.65 mm(2) for 150 pulses. 80% threshold eradication was not achieved with 100 pulses. The results indicate that increased efficacy of treatment is due to increased number of pulses delivered. In addition, we that showed the bacterial death rate as a function of the electrical field follows the statistical Weibull model for 150 and 300 pulses. We hypothesize that in the clinical setting, combining systemic antibacterial therapy with PEF will yield a synergistic effect leading to improved eradication of mesh infections.