Frederick Wang

Early treatment suppresses the development of spike-wave epilepsy in a rat model

Purpose: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood.

Current and potential inflammation targeted therapies in head and neck cancer.

Inflammation often exists in the tumor microenvironment and is induced by inflammatory mediators (cytokines, chemokines, and growth factors) produced by the tumor, stroma, and infiltrating cells. These factors modulate tissue remodeling and angiogenesis and actively promote tumor cell survival and chemoresistance through autocrine and paracrine mechanisms. Head and neck squamous cell carcinomas (HNSCCs) are highly inflammatory and aggressive in nature, and they express a number of cytokines and growth factors involved in inflammation. These cytokines and growth factors activate important signal transduction pathways, including NF-kappaB, JAK/STAT, and PI3K/Akt/mTOR, which regulate the expression of genes controlling growth, survival, and chemosensitivity. This review provides an update on recent advances in the understanding of the mechanisms driving cancer-related inflammation in HNSCC and on molecular targeted therapies under preclinical and clinical investigation.

Rates of Reconstruction Failure in Patients Undergoing Immediate Reconstruction With Tissue Expanders and/or Implants and Postmastectomy Radiation Therapy

OBJECTIVES Mastectomy rates for breast cancer have increased, with a parallel increase in immediate reconstruction. For some women, tissue expander and implant (TE/I) reconstruction is the preferred or sole option. This retrospective study examined the rate of TE/I reconstruction failure (ie, removal of the TE or I with the inability to replace it resulting in no final reconstruction or autologous tissue reconstruction) in patients receiving postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS Between 2004 and 2012, 99 women had skin-sparing mastectomies (SSM) or total nipple/areolar skin-sparing mastectomies (TSSM) with immediate TE/I reconstruction and PMRT for pathologic stage II to III breast cancer. Ninety-seven percent had chemotherapy (doxorubicin and taxane-based), 22% underwent targeted therapies, and 78% had endocrine therapy. Radiation consisted of 5000 cGy given in 180 to 200 cGy to the reconstructed breast with or without treatment to the supraclavicular nodes. Median follow-up was 3.8 years. RESULTS Total TE/I failure was 18% (12% without final reconstruction, 6% converted to autologous reconstruction). In univariate analysis, the strongest predictor of reconstruction failure (RF) was absence of total TE/I coverage (acellular dermal matrix and/or serratus muscle) at the time of radiation. RF occurred in 32.5% of patients without total coverage compared to 9% with coverage (P=.0069). For women with total coverage, the location of the mastectomy scar in the inframammary fold region was associated with higher RF (19% vs 0%, P=.0189). In multivariate analysis, weight was a significant factor for RF, with lower weight associated with a higher RF. Weight appeared to be a surrogate for the interaction of total coverage, thin skin flaps, interval to exchange, and location of the mastectomy scar. CONCLUSIONS RFs in patients receiving PMRT were lowered with total TE/I coverage at the time of radiation by avoiding inframammary fold incisions and with a preferred interval of 6 months to exchange.

The Impact of Radiation Therapy, Lymph Node Dissection, and Hormonal Therapy on Outcomes of Tissue Expander-Implant Exchange in Prosthetic Breast Reconstruction.

Background: Total skin-sparing mastectomy, with preservation of the nipple-areola complex, must account for adjuvant medical and surgical treatments for cancer. The authors assessed risk factors for complications after second-stage tissue expander–implant exchange. Methods: The authors reviewed all institutional total skin-sparing mastectomy cases that had completed tissue expander–implant exchange with at least 3 months of follow-up. They developed multivariate generalized estimating equation models to obtain adjusted relative risks of radiation therapy, type of lymph node dissection, and hormonal therapy in relation to postoperative complications. Results: The authors performed 776 cases in 489 patients, with a median follow-up of 26 months (interquartile range, 10 to 48 months). Radiation therapy was associated with increased wound breakdown risk [relative risk (RR), 3.3; 95 percent CI, 2.0 to 5.7]; infections requiring oral antibiotics (RR, 2.2; 95 percent CI, 1.31 to 3.6), intravenous antibiotics (RR, 6.4; 95 percent CI, 3.9 to 10.7), or procedures (RR, 8.9; 95 percent CI, 4.5 to 17.5); implant exposure (RR, 3.9; 95 percent CI, 1.86 to 8.3); and implant loss (RR, 4.2; 95 percent CI, 2.4 to 7.4). Axillary lymph node dissection was associated with an increased risk of implant loss (RR, 2.0; 95 percent CI, 1.11 to 3.7) relative to sentinel lymph node biopsy. Conclusions: Axillary lymph node dissection increases the risk of implant loss compared with sentinel lymph node biopsy, independent of radiation therapy. Patients who require axillary lymph node dissection may be encouraged to undergo breast conservation or autologous reconstruction when possible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Immediate implant-based breast reconstruction following total skin-sparing mastectomy in women with a history of augmentation mammaplasty: assessing the safety profile.

Background: Preservation of the nipple–areolar complex with total skin-sparing mastectomy is becoming a popular mastectomy technique. As experience increases, the patient inclusion criteria for total skin sparing mastectomy expand. The authors assessed outcomes of total skin-sparing mastectomy and immediate prosthetic reconstruction in women with a prior history of augmentation mammaplasty. Methods: Between 2005 and 2012, all women with a history of augmentation mammaplasty and implants in place, undergoing total skin-sparing mastectomy and immediate prosthetic reconstruction, were prospectively tracked. Patient demographics, expander coverage type, adjuvant treatment, and incidence of complications were analyzed. Outcomes in these patients were compared with those of patients undergoing the same operation, without prior augmentation history. Results: Thirty-four women with prior augmentation underwent total skin-sparing mastectomy and immediate tissue expander placement on 51 breasts. Comparison to the nonaugmentation group showed similar rates of superficial nipple necrosis (0 percent, p = 0.324), complete nipple necrosis (0 percent, p = 0.324), and skin flap necrosis (4 percent, p = 1.0). The prior augmentation group did have a higher rate of implant loss (10 percent, p = 0.515), with all but one of these occurring in irradiated patients. Conclusions: Total skin-sparing mastectomy and immediate prosthetic reconstruction is a safe technique in women with a history of augmentation mammaplasty. The preferred reconstructive technique is immediate submuscular tissue expander placement. In the setting of no radiation history, this operation carries a safety profile similar to that of patients without a history of prior augmentation, and can be offered safely. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Tissue Expander Reconstruction After Total Skin-Sparing Mastectomy: Defining the Effects of Coverage Technique on Nipple/Areola Preservation.

BackgroundTotal skin-sparing mastectomy (TSSM) has become increasingly frequent in recent years, as inclusion criteria continue to expand. Options for tissue expander coverage in these patients include complete submuscular tissue expander coverage and acellular dermal matrix (ADM)–assisted coverage. This study compares both techniques with regard to relevant outcomes, during a recent 1-year period at our institution. MethodsAll women undergoing TSSM and immediate expander placement between January 2012 and January 2013 were prospectively tracked. Patient demographics, expander coverage type, adjuvant treatment, length and characteristics of expansion, and incidence of complications were analyzed. ResultsIn 1 year, 127 patients underwent TSSM on 202 breasts. Overall, 113 expanders underwent submuscular coverage, and 89 underwent ADM-assisted coverage. Mean intraoperative fill volume was 52 mL in the submuscular cohort and 205 mL in the ADM cohort (P = 0.0001). Mean tissue expander size was 404 mL in the submuscular cohort and 454 mL in the ADM cohort (P = 0.0002). &khgr;2 analysis demonstrated no differences between the cohorts in incidence of complications, including partial/complete nipple necrosis. ConclusionsThe use of ADM for expander coverage after TSSM allowed for greater initial expander fill. With large and ptotic breasts, this allows for reduced incidence of skin folds in the preserved breast skin pocket, and greater control over final nipple position, as the amount of loose, mobile skin is reduced by the greater initial fill. The safety profile of ADM use after TSSM is equivalent to that of submuscular coverage, with no differences in partial or complete nipple necrosis.

Lessons learned from the American College of Surgeons National Surgical Quality Improvement Program Database: has centralized data collection improved immediate breast reconstruction outcomes and safety?

Background: The American College of Surgeons National Surgical Quality Improvement Program database was implemented to longitudinally track surgical 30-day surgical outcomes and complications. The authors analyze the program-reported outcomes for immediate breast reconstruction from 2007 to 2011, to assess whether longitudinal data collection has improved national outcomes and to highlight areas in need of continued improvement. Methods: The authors reviewed the database from 2007 to 2011 and identified encounters for immediate breast reconstruction using Current Procedural Terminology codes for prosthetic and autologous reconstruction. Demographics and comorbidities were tabulated for all patients. Postoperative complications analyzed included surgical-site infection, wound dehiscence, implant or flap loss, pulmonary embolism, and respiratory infections. Results: A total of 15,978 patients underwent mastectomy and immediate reconstruction. Fewer smokers underwent immediate reconstruction over time (p = 0.126), whereas more obese patients (p = 0.001) and American Society of Anesthesiologists class 3 and 4 patients (p < 0.001) underwent surgery. An overall increase in superficial surgical-site infection was noted, from 1.7 percent to 2.3 percent (p = 0.214). Wound dehiscence (p = 0.036) increased over time, whereas implant loss (p = 0.015) and flap loss (p = 0.012) decreased over time. Mean operative times increased over the analyzed years, as did all complications for prosthetic and autologous reconstruction. Conclusions: The American College of Surgeons National Surgical Quality Improvement Program data set has shown an increase in complications for immediate breast reconstruction over time, because of a longitudinally higher number of comorbid patients and longer operative times. This knowledge allows plastic surgeons the unique opportunity to improve patient selection criteria and efficiency. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

The impact of breast mass on outcomes of total skin-sparing mastectomy and immediate tissue expander-based breast reconstruction.

Background: Larger breast size has been viewed as a relative contraindication for nipple/areola preservation with mastectomy. Few studies have directly evaluated the effect of quantified breast size on postoperative outcomes. Methods: The authors reviewed and assessed 325 total skin-sparing mastectomy cases performed in 224 patients with immediate tissue expander placement that had documented mastectomy specimen mass. Cases were divided into two groups based on having larger (>352 grams) or smaller (⩽352 grams) breast mass. Results: Patients in the larger group had a mean body mass index that was 3.6 kg/m2 greater (p < 0.001). Overall, the larger group had an 8.1 percent increase in risk of superficial nipple necrosis (adjusted relative risk 4.0; 95 percent CI, 1.5 to 10.3). There were non-significant trends toward a 4.3 percent increase in risk of minor skin necrosis (adjusted relative risk 2.0; 95 percent CI, 0.7 to 6.4) and a 4.4 percent increase in risk of wound breakdown (adjusted relative risk 1.8; 95 percent CI, 0.8 to 3.7) with larger breast mass. Stratifying by radiation exposure, there was a non-significant trend toward a 5.4 percent increase in risk of wound breakdown (adjusted relative risk 2.9; 95 percent CI, 0.9 to 8.8) with larger breast mass in the stratum without radiation exposure. Conclusions: Larger breast mass was associated with an increased risk of superficial nipple necrosis and trends toward increased risks of minor skin necrosis and wound breakdown. Larger breast mass was not associated with an increased risk of nipple or skin flap necrosis requiring operative management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Postoperative Prophylactic Antibiotic Use following Ventral Hernia Repair with Placement of Surgical Drains Reduces the Postoperative Surgical-Site Infection Rate.

Background: To help prevent complications after incisional ventral hernia repair, traditional teaching has recommended using closed suction drains. However, some studies suggest that there is an increased infection risk with use of surgical drains, and it is uncertain whether use of extended postoperative prophylactic antibiotics while drains remain in place helps prevent surgical-site infections. Evidence guiding surgeons’ clinical practice regarding antibiotic use following hernia repair is lacking. Methods: The authors sought to determine whether the use of extended postoperative antibiotic prophylaxis beyond standard Surgical Care Improvement Project guidelines with closed-suction surgical drain placement in incisional ventral hernia repair reduces the incidence of postoperative surgical-site infections. A retrospective review of 234 patients who underwent an incisional ventral hernia repair from 2003 to 2013 at a single institution was performed. Demographic, preoperative, operative, and postoperative data were collected and analyzed. Results: Extended postoperative prophylactic antibiotics significantly reduce the incidence of postoperative surgical-site infections (OR, 0.31; p < 0.01). The odds ratio, when stratified by Ventral Hernia Working Group Scale, was 0.63, 0.25, 0.30, and 0.13 (p < 0.001 by the Mantel-Haenszel combined test) for grades 1, 2, 3, and 4, respectively, but was not statistically significant for differences between hernia grades. However, as the hernia grade increased, the odds ratio tended to decrease, suggesting that extended prophylactic antibiotics may be more effective at decreasing the incidence of surgical-site infections at higher grades. Conclusion: Extended antibiotic prophylaxis reduces surgical site infection risk following complex ventral hernia repairs, and should be considered in all cases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Do Prolonged Prophylactic Antibiotics Reduce the Incidence of Surgical-Site Infections in Immediate Prosthetic Breast Reconstruction?

Background: Approximately 50,000 women in the United States undergo mastectomy and immediate prosthetic breast reconstruction annually, and most receive postoperative prophylactic antibiotics. The effect of these antibiotics on the risk of surgical-site infections remains unclear. Methods: The authors searched the Medline, Embase, and Cochrane Library databases for studies that compared less than 24 hours and greater than 24 hours of antibiotics following immediate prosthetic breast reconstruction. Primary outcomes were surgical-site infections and implant loss. Conservative random effects models were used to obtain pooled relative risk estimates. Results: The authors identified 927 studies, but only four cohort studies and one randomized controlled trial met their inclusion criteria. Unadjusted incidences of surgical-site infections were 14 percent with more than 24 hours of antibiotics, 19 percent with less than 24 hours of antibiotics, and 16 percent overall. Unadjusted incidences of implant loss were 8 percent with more than 24 hours of antibiotics, 10 percent with less than 24 hours of antibiotics, and 9 percent overall. The pooled relative risk of implant loss was 1.17 (95 percent CI, 0.39 to 3.6) with less than 24 hours of antibiotics, which was not statistically significant. Conclusions: Prolonged antibiotic use did not have a statistically significant effect on reducing surgical-site infections or implant loss. There was significant heterogeneity between studies, and prolonged antibiotics may have increased the risk of implant loss in the randomized controlled trial. Definitive evidence may only be obtained with data from more prospective randomized controlled trials.