Searched for: Department/Unit:Plastic Surgery
Apoptosis in a rodent model of cranial suture fusion: in situ imaging and gene expression analysis
Fong, Kenton D; Song, HanJoon M; Nacamuli, Randall P; Franc, Benjamin L; Mari, Carina; Fang, Tony D; Warren, Stephen M; Contag, Christopher H; Blankenberg, Francis G; Longaker, Michael T
Craniosynostosis, the premature fusion of cranial sutures, is one of the most common craniofacial anomalies, with a reported incidence of up to one in 2500 live births. Despite its prevalence, the cause of craniosynostosis remains unknown. Previously, apoptosis has been postulated to be a contributing factor in the pathogenesis of craniosynostosis, although the role of programmed cell death in cranial sutures is poorly understood. To address this problem, the authors used an established rodent model of posterior-frontal suture fusion and sagittal suture patency to globally examine apoptosis in cranial sutures. Apoptosis was evaluated by systemically coinjecting Sprague-Dawley rats with both fluorescent and technetium-99m-labeled annexin V at time points before, during, and after the period of predicted posterior-frontal suture fusion to determine the magnitude and time course of overall apoptotic activity in both fusing and patent sutures. Using these novel in situ imaging techniques, the authors observed a significant increase in the overall levels of apoptosis in both the posterior-frontal and sagittal suture complexes during the period of predicted posterior-frontal suture fusion. To further explore this increase in apoptotic activity, they used microarray technology to study apoptosis-related genes within the suture complex. Interestingly, there was activation of distinct apoptotic pathways in the posterior-frontal and sagittal sutures during the period of predicted posterior-frontal suture fusion. Whereas increased transcription of genes associated with the mitochondria-mediated apoptotic pathway occurred in the posterior-frontal suture during fusion, activation of genes associated with the death receptor-mediated apoptotic pathway predominated in the patent sagittal suture during the same time period. These data suggest that although overall apoptotic activity in rat patent and fusing sutures is similar, the pathways mediating apoptosis within each suture are distinct
PMID: 15253194
ISSN: 0032-1052
CID: 69658
A 10-year retrospective review of 758 DIEP flaps for breast reconstruction
Gill, Paul S; Hunt, John P; Guerra, Aldo B; Dellacroce, Frank J; Sullivan, Scott K; Boraski, Jonathan; Metzinger, Stephen E; Dupin, Charles L; Allen, Robert J
This study examined 758 deep inferior epigastric perforator flaps for breast reconstruction, with respect to risk factors and associated complications. Risk factors that demonstrated significant association with any breast or abdominal complication included smoking (p = 0.0000), postreconstruction radiotherapy (p = 0.0000), and hypertension (p = 0.0370). Ninety-eight flaps (12.9 percent) developed fat necrosis. Associated risk factors were smoking (p = 0.0226) and postreconstruction radiotherapy (p = 0.0000). Interestingly, as the number of perforators increased, so did the incidence of fat necrosis. There were only 19 cases (2.5 percent) of partial flap loss and four cases (0.5 percent) of total flap loss. Patients with 45 flaps (5.9 percent) were returned to the operating room before the second-stage procedure. Patients with 29 flaps (3.8 percent) were returned to the operating room because of venous congestion. Venous congestion and any complication were observed to be statistically unrelated to the number of venous anastomoses. Overall, postoperative abdominal hernia or bulge occurred after only five reconstructions (0.7 percent). Complication rates in this large series were comparable to those in retrospective reviews of pedicle and free transverse rectus abdominis musculocutaneous flaps. Previous studies of the free transverse rectus abdominis musculocutaneous flap described breast complication rates ranging from 8 to 13 percent and abdominal complication rates ranging from 0 to 82 percent. It was noted that, with experience in microsurgical techniques and perforator selection, the deep inferior epigastric perforator flap offers distinct advantages to patients, in terms of decreased donor-site morbidity and shorter recovery periods. Mastery of this flap provides reconstructive surgeons with more extensive options for the treatment of postmastectomy patients
PMID: 15083015
ISSN: 0032-1052
CID: 73187
Reconstruction of a partial mastectomy defect with the superficial inferior epigastric artery (SIEA) flap [Case Report]
Rizzuto, Richard P; Allen, Robert J
A case in which a superficial inferior epigastric artery (SIEA) flap was used to reconstruct a partial mastectomy defect is described. The SIEA vessels have been shown to be predictable and to match well with the recipient internal mammary vessels. In addition, this flap does not require opening of the anterior rectus sheath, and it is possible to design a smaller flap, which would allow closure at the donor site without translocation of the umbilicus. The risk of developing an abdominal hernia or bulge is therefore nonexistent, and a very low and more inconspicuous scar is produced, both of which are advantages for the patient
PMID: 15356762
ISSN: 0743-684x
CID: 73188
Design and care of helmets in postoperative craniosynostosis patients: our personal approach
Jimenez, David F; Barone, Constance M; McGee, Maria E
Since 1997, the authors have instituted the use of custom-made helmets to correct craniofacial deformities associated with craniosynostosis following endoscopic-assisted craniectomies of the stenosed sutures in infants. This article presents their experience and results using helmet therapy in their patient population
PMID: 15219753
ISSN: 0094-1298
CID: 134794
Endoscopic approach to coronal craniosynostosis
Barone, Constance M; Jimenez, David F
Seventy-two patients who presented with nonsyndromic coronal craniosynostosis were treated using endoscopic-assisted techniques. Release of the stenosed suture was accomplished with the creation of a 5-mm osteotomy extending from the anterior fontanelle to the pterion. All patients tolerated the procedure well with no mortalities, morbidities, or need for blood transfusions. Correction of the vertical dystopia, nasal deviation, and orbital resection was accomplished in most cases. This approach offers a viable alternative for the early treatment of coronal craniosynostosis
PMID: 15219748
ISSN: 0094-1298
CID: 134793
Mechanobiology of mandibular distraction osteogenesis: experimental analyses with a rat model
Loboa, Elizabeth G; Fang, Tony D; Warren, Stephen M; Lindsey, Derek P; Fong, Kenton D; Longaker, Michael T; Carter, Dennis R
We analyzed mechanobiological influences on successful distraction osteogenesis (DO). Mandibular distraction surgeries were performed on 15 adult male Sprague-Dawley rats. Animals underwent gradual distraction (GD), progressive lengthening by small increments (5-day latency followed by 0.25 mm distractions twice daily for 8 days followed by 28-day maturation period). Distracted hemimandibles were harvested on postoperative days (POD) 5, 7, 10, 13, and 41. Load-displacement curves were then recorded for ex vivo distractions of 0.25 mm and stresses determined. Histologically, new bone formation appeared in GD specimens on distraction day 2 (POD 7), filling 50-60% of the gap by distraction day 8 (POD 13), with nearly complete bony bridging at end maturation (POD 41). Average tensile strains imposed by each incremental distraction ranged from approximately 10% to 12.5% during distraction days 2-8 and were associated with bone apposition rates of about 260 microm/day. Because this GD protocol was previously determined to be optimal for DO, we conclude that strains within this range provide an excellent environment for de novo bone apposition. Distraction caused tissue damage in distraction day 2, 5, and 8 specimens as evidenced by distinct drops in the load/displacement curves. Taken together, our interpretation of these data is that daily distractions cause daily tissue damage which triggers new mesenchymal tissue formation
PMID: 14962812
ISSN: 8756-3282
CID: 106153
Craniopagus twins: clinical and surgical management
Goodrich, James Tait; Staffenberg, David A
CASE REPORT: We present the case of 2-year-old craniopagus twins who are in the process of undergoing a staged separation of their craniums. In addition, they will undergo a full calvarial vault remodeling to reconstruct the lacking skull and scalp tissue in each child. We elected to do a staged separation rather than a single marathon operation for various reasons, which we will detail in this report. DISCUSSION: The philosophy and surgical management of each step will be discussed along with the pros and cons behind the reasoning that was used. At the time of this report the children have undergone three of what are projected to be four stages of separation. Each of the stages has had unique characteristics and surgical judgments involved, and those will be reviewed. CONCLUSION: Successful separation of viable conjoined twins has been historically a great rarity. Successful separation of twins where both have come out of surgery without any neurological deficit remains a rare occurrence and in our mind the ultimate goal
PMID: 15197566
ISSN: 0256-7040
CID: 122289
Facial growth of adults with unoperated clefts
Shetye, Pradip R
Studies of adult patients with unoperated complete unilateral cleft lip and palate indicate that there is normal potential for maxillary growth. The maxilla in the unoperated patient is normally positioned or protruded. The protrusion of maxilla in the unoperated adult cleft patient is limited to the non-cleft side, contributing to hemifacial maxillary prognathism. Surgical scar tissue is known to interfere with the growth of the midface. Palatal surgery has more significant influence on the growth of the mid-face than the lip surgery; therefore, it is important to reduce the effect of surgery by delaying the timing of palatal surgery or changing the location of the surgical scar from the sutural areas. Delaying palatal surgery until the maxillary growth is complete is desirable but could lead to poor speech development. Therefore, it is essential to perform the palatal surgery before speech development. The other variables that affect the midface are the development genetic make-up of the cleft child, the amount of tissue deficiency, timing of surgery, surgical technique, and the skill of the surgeon. Surgeries continue to have some inhibitory effect on maxillary growth, but it is essential to recognize and perform those surgical procedures that have the least effect on growth of the maxilla. This will help minimize extensive orthodontic treatment and eliminate major secondary orthognathic surgery for correction of the abnormal growth of the maxilla
PMID: 15145676
ISSN: 0094-1298
CID: 130355
Evaluation of pain in patients with oral squamous cell carcinoma
Connelly, S Thaddeus; Schmidt, Brian L
In this study we have developed and tested a novel pain questionnaire to measure the pain experienced by patients with oral squamous cell carcinoma. The questionnaire consisted of 8 questions rated by the patient on a visual analog scale. Patients completed the questionnaire at the time of initial presentation before surgical treatment. None of the patients were taking analgesics. The responses were then scored and compiled with patient data and pathology reports. Of the 15 completed questionnaires, 14 patients reported some level of functional restriction from pain (mean, 46.6 +/- 25.2, scale of 0 to 100 mm). On average, patients experienced significantly higher function-related, rather than spontaneous, pain intensity and sharpness. Men (n = 8) had a significantly higher level of function-related pain intensity and sharpness than women had (n = 7). There was a strong correlation between nodal disease and increased levels of spontaneous intensity, sharpness, throbbing, and overall functional restriction. PERSPECTIVE: The results of this study indicate the heterogeneous nature and function dependence of oral cancer pain. The questionnaire we have developed in this study will allow for correlations between pain parameters and specific tumor biology in future studies
PMID: 15556829
ISSN: 1526-5900
CID: 132045
Overexpression of matrix metalloproteinase-1 and -9 mRNA is associated with progression of oral dysplasia to cancer
Jordan, Richard C K; Macabeo-Ong, Maricris; Shiboski, Caroline H; Dekker, Nusi; Ginzinger, David G; Wong, David T W; Schmidt, Brian L
PURPOSE: Although an important risk factor for oral cancer is the presence of epithelial dysplasia, many lesions will not progress to malignancy. Matrix metalloproteinases (MMPs) are zinc-dependent proteinases capable of digesting various structural components of the extracellular matrix. Because MMPs are frequently overexpressed in oral squamous cell carcinoma (SCC), we hypothesized that they are also overexpressed in oral dysplasias; we also hypothesized that those dysplasias that progress to oral cancer express higher levels of MMPs than those lesions that do not progress. EXPERIMENTAL DESIGN: In this retrospective study, we examined changes in MMP-1, -2, and -9 mRNA expression using quantitative TaqMan reverse transcription-polymerase chain reaction in 34 routinely processed oral dysplasias and 15 SCCs obtained from 34 patients. After several years of close follow-up, 19 dysplasias progressed to oral SCC and 15 did not. RESULTS: Overall, MMP-1 mRNA was overexpressed (>2-fold) in 24 of 34 (71%) dysplasias and 13 of 15 (87%) oral SCCs. MMP-2 overexpression was seen in 11 of 34 (32%) dysplasias and 7 of 15 (47%) cancers; for MMP-9, overexpression was identified in 29 of 34 (85%) dysplasias and 15 of 15 (100%) cancers. MMP-1 and -9 levels were significantly higher in the SCCs compared with all oral dysplasias (P = 0.004 and P = 0.01, respectively). MMP-1 and -9 mRNA levels were significantly higher in the oral dysplasias that progressed to oral cancer compared with those that did not (P = 0.04 and P = 0.002, respectively). CONCLUSIONS: Levels of MMP-1 and -9 mRNA may be markers of malignant transformation of oral dysplasia to oral cancer
PMID: 15475433
ISSN: 1078-0432
CID: 132046