Thomas Satterwhite

Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation1

Background. Corticosteroids have been invariant transplant immunosuppressives with numerous adverse effects. We previously reported 6-month results in 10 patients using extended daclizumab induction to safely eliminate steroid use in pediatric renal transplantation. This expanded pilot series discusses immunosuppression dosing modification to further minimize drug toxicity without sacrificing regimen efficacy. Methods. Fifty-seven pediatric renal transplant recipients were enrolled in the pilot steroid-free protocol. Extended daclizumab induction, tacrolimus, and mycophenolate mofetil (MMF) were intended maintenance drugs. Fourteen patients were equal to or younger than 5 years, and 43 patients were older than 5 years of age at transplantation. There were seven protocol breaks. Study patients underwent serial protocol transplant biopsies (n=246), and serum daclizumab and mycophenolic acid (MPA) trough levels were evaluated. In this efficacy study, controls were 50 historical-matched steroid-based children receiving tacrolimus with 100% 2-year graft survival and without delayed graft function. Results. Mean follow-up was 20 (range, 4.5–41) months with 98% overall graft and patient survival. At 1 year of analysis, steroid-free recipients showed significant improvements for clinical acute rejection (8%), graft function, hypertension, and growth, without increased infectious complications. Leukopenia, anemia, and allograft nephrotoxicity were addressed by solely decreasing MMF and tacrolimus dosing and/or by replacing MMF with sirolimus, without increasing acute rejection. Early daclizumab levels of more than 5 &mgr;g/mL were observed for the first time in children of all ages. Conclusions. Pediatric renal transplantation is safe without steroids. Daclizumab first-dose doubling and extended use for 6 months replaces steroids effectively without evidence of overimmunosuppression and may be the pivotal cause for the reduced acute rejection seen in this trial. This pilot study provides preliminary data to test this protocol in a prospective, multicenter randomized study.

Outcomes of complex abdominal herniorrhaphy: experience with 106 cases.

Purpose:Reconstruction of abdominal wall defects is a challenging problem. Often, the surgeon is presented with a patient having multiple comorbidities, who has already endured numerous unsuccessful operations, leaving skin and fascia that are attenuated and unreliable. Our study investigated preoperative, intraoperative, and postoperative factors and techniques during abdominal wall reconstruction to determine which variables were associated with poor outcomes. Methods:Data were collected on all patients who underwent ventral abdominal hernia repair by 3 senior-level surgeons at our institution during an 8-year period. In all cases, placement of either a synthetic or a biologic mesh was used to provide additional reinforcement of the repair. Results:A total of 106 patients were included. Seventy-nine patients (75%) had preoperative comorbid conditions. Sixty-seven patients developed a postoperative complication (63%). Skin necrosis was the most common complication (n = 21, 19.8%). Other complications included seroma (n = 19, 17.9%), cellulitis (n = 19, 17.9%), abscess (n = 14 13.2%), pulmonary embolus/deep vein thrombosis (n = 3, 2.8%), small bowel obstruction (n = 2, 1.9%), and fistula (n = 8, 7.5%). Factors that significantly contributed to postoperative complications (P < 0.05) included obesity, diabetes, hypertension, fistula at the time of the operation, a history of >2 prior hernia repairs, a history of >3 prior abdominal operations, hospital stay for >14 days, defect size > 300 square cm, and the use of human-derived mesh allograft. Factors that significantly increased the likelihood of a hernia recurrence (P < 0.05) included a history of >2 prior hernia repairs, the use of human-derived allograft, using an overlay-only mesh placement, and the presence of a postoperative complication, particularly infection. Hernia recurrences were significantly reduced (P < 0.05) by using a “sandwich” repair with both a mesh overlay and underlay and by using component separation. Conclusions:A history of multiple abdominal operations is a major predictor of complications and recurrences. If needed, component separation should be used to achieve primary tension-free closure, which helps to reduce the likelihood of hernia recurrences. Our data suggest that mesh reinforcement used concomitantly in a “sandwich” repair with component separation release may lead to reduced recurrence rates and may provide the optimal repair in complex hernia defects.

Increased expression of cytotoxic effector molecules: Different interpretations for steroid‐based and steroid‐free immunosuppression

Abstract: Cytotoxic T lymphocyte (CTL) effector molecules have been studied as markers of acute rejection in renal allograft recipients on steroid‐based immunosuppression. We hypothesized that basal CTL gene expression may vary with time post‐transplantation as well as with different immunosuppression protocols (steroid‐based or steroid‐free). Variations in CTL gene expression may thus impact on the ability to predict acute allograft rejection. We used the non‐invasive method of quantitative competitive‐reverse transcription‐polymerase chain reaction (QC‐RT‐PCR) to quantify the amounts of CTL effector molecules (granulysin, GL; perforin, P; granzyme B, GB) in serial peripheral blood lymphocyte (PBL) samples from steroid‐free and steroid‐based adult and pediatric renal allograft recipients. Patients on both protocols were clinically monitored by protocol biopsies at 1, 3, 6, and 12 months post‐transplantation and for graft function at 1 yr post‐transplantation in a separate clinical study. Steroid‐free patients with stable graft function showed an increase in GL, P, and GB gene expression over time post‐transplantation with the increase being seen largely by the first post‐transplant month. A further increase in GL expression was noted at the end of the first post‐transplant year in the absence of acute rejection, whereas GB and P levels were unchanged. At comparative time‐points post‐transplantation, CTL genes were found to be higher in steroid‐free patients with stable graft function, compared to steroid‐based recipients with either clinically stable graft function or acute rejection. This study suggests that levels of CTL gene expression, although important in a steroid‐based regimen to monitor the risk of acute rejection, may not be similarly applied in patients on steroid‐free immunosuppression. The early increase in levels seen in steroid‐free patients appears to correlate with the total absence of steroids. As steroid‐free patients seem to have a lower incidence of acute rejection and better long‐term graft function at 1 yr, the early increase in CTL genes in the absence of acute rejection may suggest an early adaptive immune activation response, promoting early graft acceptance in this protocol.

Microsurgery education in residency training: validating an online curriculum.

Introduction:Plastic surgery training has traditionally been modeled as an “apprenticeship,” where faculty teach surgical skills to residents on live patients. Although this is a well-established process, the demand by the public and healthcare agencies for improved patient care, outcomes, and patient safety has led to the development of adjunct methods of teaching. The goal of this project is to assess the effectiveness of a web-based microsurgical curriculum. Methods:We developed an interactive Web site to teach essential microsurgical competencies. Residents were randomly divided into 2 cohorts: one experimental group completed this online resource and the other control group did not. Pre- and postassessments were administered, consisting of a written test and a recorded microsurgery skills session. Results:A total of 17 plastic surgery residents of various training levels participated in the study. Residents who completed the web-based curriculum showed dramatic improvement in their knowledge and skills, with a 17-percentage point increase in their test scores (P = 0.01) compared with controls (P = 0.80). The experimental group was more likely to perform microanastomoses faster with an average of 4.5-minute improvement compared with 1.25-minute change among the control group. Residents performed self-assessments, and those who rated themselves as “very confident” had higher overall test scores (85% test score vs. 59%, P = 0.004), as well as shorter times to complete the microsurgical task (7.5 minutes vs. 13.6 minutes, P = 0.007). Overall, 62% of residents rated the online webpage as extremely valuable. The majority of residents reported the webpage improved their knowledge and markedly improved their microsurgical technique, which was confirmed by faculty experts. Conclusions:Our interactive Web-based curriculum is a novel resource, teaching microsurgery in an organized, competency-based manner, which we believe is the first Web site of this nature. An individualized, self-paced Web site is ideal for plastic surgery trainees of all levels. Overall, the widespread implementation of our proposed curriculum—online self-directed training combined with regular practice sessions—will establish a strong foundation of microsurgery knowledge and skills acquisition for all plastic surgery residents.

Laparoscopic Roux-en-Y Gastric Bypass: Differences in Outcome between Attendings and Assistants of Different Training Backgrounds

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is associated with a significant learning curve. We hypothesize that differences in surgeon and assistant training backgrounds may significantly impact outcomes during the learning curve. Methods: Retrospective analysis was performed on patients undergoing LRYGBP at an academic medical center between January 1998 and August 2003. Operations were performed by surgeons with different training backgrounds: without formal laparoscopic fellowship (S1, n=95); immediately following laparoscopic fellowship (S2, n=100); and with extensive laparoscopic experience post fellowship (S3, n=88). First assistants were attendings, fellows, or residents. The variables analyzed included demographics, operative times, estimated blood loss (EBL), rate of conversion, length of stay (LOS), ICU stay, re-operation/re-admission rate, and complications. Results were analyzed by ANOVA and Fishers exact test. Results: There were significant differences among surgeons of different training backgrounds in EBL, LOS, rate of ICU admission, and intraoperative and late complications rates. Among assistants of different training levels, there were significant differences in operative time, EBL, intraoperative complication rates and re-admission rates. Conclusions: Differences in training background of the surgeons resulted in significant differences in outcome, including EBL, LOS, ICU admission and intraoperative and late complication rates. Lower assistant training levels significantly impacted efficiency through lengthened operative times and increased EBL, as well as increased intraoperative complication rates and re-admission rates. Our results suggested that participating in a laparoscopic fellowship and operating with a more experienced assistant may improve outcomes during the learning curve.

Facial Feminization: Systematic Review of the Literature

Background: Facial feminization surgery encompasses a broad range of craniomaxillofacial surgical procedures designed to change masculine facial features into feminine features. The surgical principles of facial feminization surgery can be applied to male-to-female transsexuals and anyone desiring feminization of the face. Although the prevalence of these procedures is difficult to quantify, because of the rising prevalence of transgenderism (approximately one in 14,000 men) along with improved insurance coverage for gender-confirming surgery, surgeons versed in techniques, outcomes, and challenges of facial feminization surgery are needed. This review is designed to critically appraise the current facial feminization surgery literature. Methods: A comprehensive literature search of the Medline, PubMed, and EMBASE databases was conducted for studies published through October of 2014 with multiple search terms related to facial feminization. Data on techniques, outcomes, complications, and patient satisfaction were collected. Results: Fifteen articles were selected and reviewed from the 24 identified, all of which were either retrospective or case series/reports. Articles covered a variety of facial feminization procedures. A total of 1121 patients underwent facial feminization surgery, with seven complications reported, although many articles did not explicitly comment on complications. Satisfaction was high, although most studies did not use validated or quantified approaches to address satisfaction. Conclusions: Facial feminization surgery appears to be safe and satisfactory for patients. Further studies are required to better compare different techniques to more robustly establish best practices. Prospective studies and patient-reported outcomes are needed to establish quality-of-life outcomes for patients. However, based on these studies, it appears that facial feminization surgery is highly efficacious and beneficial to patients.

Long-Term Outcomes of Rectosigmoid Neocolporrhaphy in Male-to-Female Gender Reassignment Surgery.

Background: Favorable outcomes of rectosigmoid neocolporrhaphy have previously been reported. Unfortunately, rectosigmoid transfers are still perceived negatively, usually relegated to secondary vaginoplasties. This study aims to provide an objective investigation into the safety and efficacy of rectosigmoid neocolporrhaphy for vaginoplasty in male-to-female transsexual patients. Methods: A retrospective review was performed on male-to-female patients who had undergone rectosigmoid neocolporrhaphy performed by the senior author. Patient data including demographics, medical history, complications, and the need for revision surgery were obtained. Direct inquires were conducted to determine patients’ level of satisfaction with appearance, sexual function, and ease of postoperative recovery. Results: Eighty-three patients were included over the course of 22 years, with an average clinical follow-up of 2.2 years (83 patients) and phone interview follow-up of 23 years (21 patients). Overall, the patients were healthy, with minimal comorbidities. Forty-eight patients (58 percent) had complications, but the majority (83.3 percent) were minor and consisted mainly of introital stricture or excessive protrusion of the corpus spongiosum. Smoking was associated with higher complication rates (p = 0.05), especially stricture formation. Excessive mucorrhea occurred in 28.6 percent but resolved after the first year. Overall patient satisfaction with appearance and sexual function was high. Conclusions: This study is one of the largest and longest reported series of rectosigmoid transfers for vaginoplasty in transsexual patients. Rectosigmoid neocolporrhaphies have many times been recommended for secondary or revision surgery when other techniques, such as penile inversion, have failed. However, the authors believe the rectosigmoid transfer is safe and efficacious, and it should be offered to male-to-female patients for primary vaginoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Stanford Microsurgery and Resident Training (SMaRT) Scale: validation of an on-line global rating scale for technical assessment.

IntroductionWe previously reported results of our on-line microsurgery training program, showing that residents who had access to our website significantly improved their cognitive and technical skills. In this study, we report an objective means for expert evaluators to reliably rate trainees’ technical skills under the microscope, with the use of our novel global rating scale. Methods“Microsurgery Essentials” (http://smartmicrosurgery.com) is our on-line training curriculum. Residents were randomly divided into 2 groups: 1 group reviewed this online resource and the other did not. Pre- and post-tests consisted of videotaped microsurgical sessions in which the trainee performed “microsurgery” on 3 different models: latex glove, penrose drain, and the dorsal vessel of a chicken foot. The SMaRT (Stanford Microsurgery and Resident Training) scale, consisting of 9 categories graded on a 5-point Likert scale, was used to assess the trainees. Results were analyzed with ANOVA and Student t test, with P less than 0.05 indicating statistical significance. ResultsSeventeen residents participated in the study. The SMaRT scale adequately differentiated the performance of more experienced senior residents (PGY-4 to PGY-6, total average score = 3.43) from less experienced junior residents (PGY-1 to PGY-3, total average score = 2.10, P < 0.0001). Residents who viewed themselves as being confident received a higher score on the SMaRT scale (average score 3.5), compared to residents who were not as confident (average score 2.1) (P < 0.001). There were no significant differences in scoring among all 3 evaluators (P > 0.05). Additionally, junior residents who had access to our website showed a significant increase in their graded technical performance by 0.7 points when compared to residents who did not have access to the website who showed an improvement of only 0.2 points (P = 0.01). ConclusionsOur SMaRT scale is valid and reliable in assessing the microsurgical skills of residents and other trainees. Current trainees are more likely to use self-directed on-line education because of its easy accessibility and interactive format. Our global rating scale can help ensure residents are achieving appropriate technical milestones.

Live imaging of Smad2/3 signaling in mouse skin wound healing

Biophotonics and real‐time imaging are novel technologies that can greatly enhance the study of complex biological processes. We applied this technology in a transgenic mouse with a luciferase reporter gene fused to a transforming growth factor‐β (TGF‐β) responsive Smad2/3‐binding element to study bioluminescence after skin wounding. Two dorsal midline excisional skin wounds were made using a biopsy punch. One wound was randomized to suture closure and the other allowed to heal by secondary intention (n=8 each wound). Bioluminescence was measured at fixed time points following surgery. Phospho‐Smad2/3 immunohistochemistry was performed to localize expression in skin wound samples. In vivo bioluminescence increased following skin wounding. Peak activity occurred on day 17 and was fourfold that of baseline (p<0.05). Subgroup analysis of primary and secondary healing showed that primarily sutured wounds had peak activities earlier than those with secondary healing, although this did not reach statistical significance. Intense phospho‐Smad2/3 staining was found in the hair follicles. In vivo bioluminescence tracks Smad2/3‐dependent TGF‐β signaling in the in vivo wound healing process. Our findings suggest that signaling increases after wound healing, which contrasts with other studies that show raised TGF‐β signaling in the initial days following wounding.

In Vitro Analysis of Transforming Growth Factor-β1 Inhibition in Novel Transgenic Sbe-luciferase Mice

Background: Transforming growth factor β1 (TGF-β1) expression correlates with scarring. A novel transgenic mouse model with a Smad2/3-responsive luciferase reporter construct (SBE-luc) has been developed. We hypothesized that bioluminescence in SBE-luc dermal fibroblasts could be measured to assess TGF-β1 inhibition. Materials and Methods: Cultured dermal fibroblasts from SBE-luc mice were treated simultaneously with TGF-β1 and increasing doses of either neutralizing antibody to TGF-β (NA-TGFβ) or SB-431542, a novel TGF-β receptor kinase inhibitor. Fibroblasts were measured for luciferase activity. SBE-luc fibroblasts underwent Western blot analysis for collagen type I production. Results: TGF-β1 produced maximal luciferase activity in SBE-luc fibroblasts at 0.1 ng/mL (P < 0.05). NA-TGFβ and SB-431542 inhibited luciferase activity in a dose-dependent fashion, with complete inhibition achieved by 0.1 μg/mL and 1 μM, respectively (P < 0.05). NA-TGFβ and SB-431542 inhibited collagen type I production. Conclusions: Our in vitro results provide validation for further in vivo real-time imaging studies using the SBE-luc mouse as a novel wound-healing model.