Faculty Bibliography

Immune suppression following major thermal injury directly impacts the recovery potential. Limited data from past reports indicate that natural killer cells might be suppressed due to a putative soluble factor that has remained elusive up to date. Here we comparatively study cohorts of patients with Major and Non-Major Burns as well as healthy donors. MICB and ULBP1 are stress ligands of NKG2D that can be induced by heat stress. Remarkably, serum concentration levels of MICB and ULBP1 are increased by 3-fold and 20-fold, respectively, already within 24h post major thermal injury, and are maintained high for 28 days. In contrast, milder thermal injuries do not similarly enhance the serum levels of MICB and ULBP1. This kinetics coincides with a significant downregulation of NKG2D expression among peripheral blood NK cells. Downregulation of NKG2D by high concentration of soluble MICB occurs in cancer patients and during normal pregnancy due to over production by cancer cells or extravillous trophoblasts, respectively, as an active immune-evasion mechanism. In burn patients this seems an incidental outcome of extensive thermal injury, leading to reduced NKG2D expression. Enhanced susceptibility of these patients to opportunistic viral infections, particularly herpes viruses, could be explained by the reduced NKG2D expression. Further studies are warranted for translation into innovative diagnostic or therapeutic technologies.

INTRODUCTION: Long-term oncologic outcomes in nipple-sparing mastectomy (NSM) continue to be defined. Rates of locoregional recurrence for skin-sparing mastectomy (SSM) and NSM in the literature range from 0% to 14.3%. We investigated the outcomes of NSM at our institution. METHODS: Patients undergoing NSM at our institution from 2006 to 2014 were identified and outcomes were analyzed. RESULTS: From 2006 to 2014, 319 patients (555 breasts) underwent NSM. One-hundered and fourty-one patients (237 breasts) had long-term follow-up available. Average patient age and BMI were 47.78 and 24.63. Eighty-four percent of patients underwent mastectomy primarily for a therapeutic indication. Average tumor size was 1.50 cm with the most common histologic type being invasive ductal carcinoma (62.7%) followed by DCIS (23.7%). Average patient follow-up was 30.73 months. There was one (0.8%) incidence of ipsilateral chest-wall recurrence. There were 0.37 complications per patient. CONCLUSIONS: We examined our institutional outcomes with NSM and found a locoregional recurrence rate of 0.8% with no nipple-areolar complex recurrence. This rate is lower than published rates for both NSM and SSM. J. Surg. Oncol. (c) 2015 Wiley Periodicals, Inc.

BACKGROUND:Common sedation options for colonoscopy include propofol alone or a combination of midazolam and fentanyl. The former usually requires the presence of an anesthesia caregiver. The strategy that optimizes patient satisfaction has not yet been determined. OBJECTIVE:This study was designed to assess whether patient satisfaction at the time of colonoscopy is equivalent for propofol compared with midazolam and fentanyl. DESIGN/METHODS:In this prospective, single-center, parallel group, single-blind, randomized, equivalence trial (NCT-01488045), 262 patients blinded to treatment received propofol (n = 126) or midazolam plus fentanyl (n = 136) at the time of colonoscopy. A patient satisfaction survey was administered in the recovery room and 1 to 5 days postprocedure. The endoscopist completed a survey immediately postprocedure. SETTINGS/METHODS:This study was conducted at a tertiary academic hospital with a dedicated colon and rectal surgery division. PATIENTS/METHODS:Patients over the age of 18 years who were undergoing elective colonoscopy were included in this study. MAIN OUTCOME MEASURES/METHODS:The primary outcome was patient satisfaction with the colonoscopy. Secondary outcomes included physician and patient perception of patient pain, physician perception of patient tolerance of and difficulty of procedure, procedure duration, percentage of patients with cecal intubation, recovery time, and adverse events. RESULTS:Patient overall satisfaction scores in the recovery room after using the combination of midazolam and fentanyl (n = 136) during colonoscopy were not equivalent to patient satisfaction scores after using propofol (n = 126) alone (mean = 83.9 and 98.0 visual analog scale points) because the 90% CI (-18.5 to -9.6) for the mean treatment difference (-14.1) was completely outside the prespecified range of equivalence (±5 visual analog scale points). Patient pain as reported by the patient and as perceived by the physician and difficulty of the procedure were significantly worse for the midazolam/fentanyl group (n = 136) compared with the propofol group (n = 126). Time in the colonoscopy suite was significantly shorter for the propofol group, but the difference was small (4 minutes). There were no significant differences in percentage with cecal intubation, recovery time, or adverse events. LIMITATIONS/CONCLUSIONS:This is a single-institution, single-endoscopist study and is limited by the inability to perform blinding of the endoscopist. CONCLUSIONS:The use of propofol for conscious sedation during colonoscopy is associated with greater patient satisfaction and less pain when compared with midazolam/fentanyl, as perceived by the patient and endoscopist.

Ionizing radiation is a common therapeutic modality and following irradiation dermal changes, including fibrosis and atrophy, may lead to permanent changes. We have previously demonstrated that occupancy of A2A receptor (A2AR) stimulates collagen production, so we determined whether blockade or deletion of A2AR could prevent radiation-induced fibrosis. After targeted irradiation (40 Gy) of the skin of wild-type (WT) or A2AR knockout (A2ARKO) mice, the A2AR antagonist ZM241385 was applied daily for 28 d. In irradiated WT mice treated with the A2AR antagonist, there was a marked reduction in collagen content and skin thickness, and ZM241385 treatment reduced the number of myofibroblasts and angiogenesis. After irradiation, there is an increase in loosely packed collagen fibrils, which is significantly diminished by ZM241385. Irradiation also induced an increase in epidermal thickness, prevented by ZM241385, by increasing the number of proliferating keratinocytes. Similarly, in A2ARKO mice, the changes in collagen alignment, skin thickness, myofibroblast content, angiogenesis, and epidermal hyperplasia were markedly reduced following irradiation. Radiation-induced changes in the dermis and epidermis were accompanied by an infiltrate of T cells, which was prevented in both ZM241385-treated and A2ARKO mice. Radiation therapy is administered to a significant number of patients with cancer, and radiation reactions may limit this therapeutic modality. Our findings suggest that topical application of an A2AR antagonist prevents radiation dermatitis and may be useful in the prevention or amelioration of radiation changes in the skin.-Perez-Aso, M., Mediero, A., Low, Y. C., Levine, J., Cronstein, B. N. Adenosine A2A receptor plays an important role in radiation-induced dermal injury.

A clinical case demonstrating the use of a free fibula osteoseptocutaneous flap for reconstruction of a high-energy ballistic mandible defect is detailed. The surgical videos highlight key nuances and pearls of flap design, harvest, dissection, and execution of microsurgical anastomosis. Attention is also given to preoperative surgical planning and postoperative care. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

BACKGROUND: Fat grafting has become popular for repair of postsurgical/postradiation defects after head/neck cancers resection. Fat graft supplementation with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve graft viability/efficacy, although the impact of ASCs on head/neck cancer cells is unknown. OBJECTIVES: To determine whether ASCs affect growth, migration, and metastasis of human head/neck cancer. METHODS: Human Cal-27 and SCC-4 head/neck cancer cells were co-cultured human ASCs, or treated with ASC conditioned medium (CM), and cancer cell growth/migration was assessed by MTT, cell count, and scratch/wound healing assays in vitro. Co-injection of 3 x 10(6) Cal-27/green fluorescent protein (GFP) cells and ASCs into the flank of NUDE mice assessed ASC effect on tumor growth/morphology. Quantitation of human chromosome 17 DNA in mouse organs assessed ASC effects on micrometastasis. Primary tumors were evaluated for markers of epithelial-to-mesenchymal transition, matrix metalloproteinases, and angiogenesis by immunohistochemistry. RESULTS: Co-culture of Cal-27 or SCC-4 cells with ASCs from 2 different donors or ASC CM had no effect on cell growth in vitro. However, ASC CM stimulated Cal-27 and SCC-4 migration. Co-injection of ASCs from 2 different donors with Cal-27 cells did not affect tumor volume at 6 weeks, but increased Cal-27 micrometastasis to the brain. Evaluation of tumors sections from 1 ASC donor co-injection revealed that ASCs were viable and well integrated with Cal-27/GFP cells. These tumors exhibited increased MMP2, MMP9, IL-8, and microvessel density. CONCLUSIONS: Human ASCs did not alter growth of human head/neck cancer cells or tumor xenografts, but stimulated migration and early micrometastasis to mouse brain.

Unilateral breast reconstruction poses a special set of challenges to the reconstructive breast surgeon compared to bilateral reconstructions. No studies to date provide an objective comparison between autologous and implant based reconstructions in matching the contralateral breast. This study compares the quantitative postoperative results between unilateral implant and autologous flap reconstructions in matching the native breast in shape, size, and projection using three-dimensional (3D) imaging. Sixty-four patients who underwent unilateral mastectomy with tissue expander (TE)-implant (n = 34) or autologous microvascular free transverse rectus abdominus myocutaneous (TRAM; n = 18) or deep inferior epigastric artery perforator (DIEP; n = 12) flap (n = 30) reconstruction from 2007 to 2010 were analyzed. Key patient demographics and risk factors were collected. Using 3D scans of patients obtained during pre and postoperative visits including over 1 year follow-ups for both groups, 3D models were constructed and analyzed for total breast volume, anterior-posterior projection from the chest wall, and 3D comparison. No significant differences in mean age, body mass index, or total number of reconstructive surgeries were observed between the two groups (TE-implant: 52.2 +/- 10, 23.9 +/- 3.7, 3 +/- 0.9; autologous: 50.7 +/- 9.4, 25.4 +/- 3.9, 2.9 +/- 1.3; p > 0.05). The total volume difference between the reconstructed and contralateral breasts in the TE-implant group was insignificant: 27.1 +/- 22.2 cc, similar to the autologous group: 29.5 +/- 24.7 cc, as was the variance of breast volume from the mean. In both groups, the reconstructed breast had a larger volume. A-P projections were similar between the contralateral and the reconstructed breasts in the TE-implant group: 72.5 +/- 3.21 mm versus 71.7 +/- 3.5 mm (p > 0.05). The autologous reconstructed breast had statistically insignificant but less A-P projection compared to the contralateral breast (81.9 +/- 16.1 mm versus 61.5 +/- 9.5 mm; p > 0.05). Variance of A-P projection from the mean was additionally insignificant between the contralateral and reconstructed breasts. Both groups produced similar asymmetry scores based on global 3D comparison (TE-implant: 2.24 +/- 0.3 mm; autologous: 1.96 +/- 0.2 mm; p > 0.05). Lastly, when the autologous group was further subdivided into TRAM and DIEP cohorts, no significant differences in breast volume, A-P projection or symmetry existed. Using 3D imaging, we demonstrate that both TE-implant and autologous reconstruction can achieve symmetrical surgical results with the same number of operations. This study demonstrates that breast symmetry, while an important consideration in the breast reconstruction algorithm, should not be the sole consideration in a patient' decision to proceed with autologous versus TE-implant reconstruction.

BACKGROUND: Postoperative wound complications in patients undergoing complex spinal surgery can have devastating sequelae, including hardware exposure, meningitis, and unplanned reoperation. The literature shows that wound complication rates in this patient population approach 19 percent and, in very high-risk patients (i.e., prior spinal surgery, existing spinal wound infection, cerebrospinal fluid leak, malignancy, or history of radiation therapy), as high as 40 percent and with reoperation rates as high as 12 percent. The authors investigated whether prophylactic closure of spinal wounds with muscle flaps improves outcomes. METHODS: A retrospective review was performed of 102 reconstructions (in 96 patients) in which spinal wound closure was performed by means of paraspinous, trapezius, or latissimus muscle advancement flaps by a single plastic surgeon (J.A.S.) from 2006 to 2014. Data regarding presurgical diagnosis, patient demographics, and incidence of postoperative complications were recorded. RESULTS: One hundred two reconstructions were included, with follow-up ranging from 2 to 60 months. Eighty-eight reconstructions were classified as very high-risk for wound complications, defined as those having prior spinal surgery, existing spinal wound infection, cerebrospinal fluid leak, malignancy, or prior radiation therapy. Within the very high-risk group, there were six wound complications (6.8 percent), three of which (3.4 percent) required reoperation. CONCLUSIONS: In this study, there is a markedly lower rate (6.8 percent) of postoperative wound complications compared with historical controls after closure of spinal wounds with local muscle flaps in very high-risk patients. These data encourage safe and routine use of muscle flaps for closure in this cohort of patients undergoing spinal surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.