Faculty Bibliography

BACKGROUND: : The graying of our population has motivated the authors to better understand age-related impairments in wound healing. To increase research throughput, the authors hypothesized that the Hutchinson-Gilford progeria syndrome Zmpste24-deficient (Zmpste24) mouse could serve as a model of senescent wound healing. METHODS: : Using a stented excisional wound closure model, the authors tested this hypothesis on 8-week-old male Zmpste24 mice (n = 25) and age-matched male C57BL/6J wild-type mice (n = 25). Wounds were measured photogrammetrically and harvested for immunohistochemistry, enzyme-linked immunosorbent assay, and quantitative real-time polymerase chain reaction, and circulating vasculogenic progenitor cells were measured by flow cytometry. RESULTS: : Zmpste24 mice had a significant delay in wound closure compared with wild-type mice during the proliferative/vasculogenic phase. Zmpste24 wounds had decreased proliferation, increased 8-hydroxy-2'-deoxyguanosine levels, increased proapoptotic signaling (i.e., p53, PUMA, BAX), decreased antiapoptotic signaling (i.e., Bcl-2), and increased DNA fragmentation. These changes correlated with decreased local vasculogenic growth factor expression, decreased mobilization of bone marrow-derived vasculogenic progenitor cells, and decreased new blood vessel formation. Age-related impairments in wound closure are multifactorial. CONCLUSIONS: : The authors' data suggest that the Hutchinson-Gilford progeria syndrome Zmpste24 progeroid syndrome shares mechanistic overlap with normal aging and therefore might provide a uniquely informative model with which to study age-associated impairments in wound closure.

Targeted therapy to prevent the progression from acute to chronic pain in cancer patients remains elusive. We developed three novel cancer models in mice that together recapitulate the anatomical, temporal, and functional characteristics of acute and chronic head and neck cancer pain in humans. Using pharmacologic and genetic approaches in these novel cancer models, we identified the interaction between protease-activated receptor 2 (PAR2) and serine proteases to be of central importance. We show that serine proteases such as trypsin induce acute cancer pain in a PAR2-dependent manner. Chronic cancer pain is associated with elevated serine proteases in the cancer microenvironment and PAR2 upregulation in peripheral nerves. Serine protease inhibition greatly reduces the severity of persistent cancer pain in wild-type mice, but most strikingly, the development of chronic cancer pain is prevented in PAR2-deficient mice. Our results demonstrate a direct role for PAR2 in acute cancer pain and suggest that PAR2 upregulation may favor the development and maintenance of chronic cancer pain. Targeting the PAR2-serine protease interaction is a promising approach to the treatment of acute cancer pain and prevention of chronic cancer pain.

This study evaluated the early biomechanical fixation and bone-to-implant contact (BIC) of an alumina-blasted/acid-etched (AB/AE) compared with an experimental resorbable blasting media (RBM) surface in a canine model. Higher texturization was observed for the RBM than for the AB/AE surface, and the presence of calcium and phosphorus was only observed for the RBM surface. Time in vivo and implant surface did not influence torque. For both surfaces, BIC significantly increased from 2 to 4 weeks.

BACKGROUND: Pathologic analysis of deep tissue obtained during debridement of venous ulcers is often unnoticed in its importance. We previously reported pathologic findings on 139 patients with venous ulcers. The objective of this study was to correlate the pathologic findings in venous ulcers with wound healing to establish a negative margin for debridement. STUDY DESIGN: Consecutive patients with a lower extremity venous ulcer present for at least 4 weeks, presenting to a single wound healing center, were included. Wounds underwent aggressive surgical debridement beyond the subcutaneous level until judged to have a viable base. Specimens were scored based on cellularity, vascularity, collagen composition, inflammation, and dense fibrosis, with a highest possible score of 13. Healing was the primary outcome for analysis. RESULTS: Of the 26 patients who met inclusion criteria, only 50% of them (13 patients) with a total of 18 venous ulcers underwent surgical debridement available for pathologic analysis. Mean ulcer area was 34.7 cm(2) at initial presentation, and 89% of patients had a continuous positive healing curve as measured by decreasing wound area (from 34.7 cm(2) to 14.3 cm(2)). However, specimens with dense fibrosis, decreased cellularity, mature collagen, and pathology score less than 10 were predominantly nonhealing ulcers. CONCLUSIONS: Presence of dense fibrosis and high levels of mature collagen in deep tissue specimens are significant correlative factors in nonhealing of venous ulcers. We recommend deep debridement on all venous ulcers that are refractory to healing until the level of absence of dense fibrosis and mature collagen is reached to promote venous ulcer healing.

ABSTRACT: Henry Kawamoto Jr and I go back a long way. Our friendship began at the Columbia-Presbyterian Medical Center. I had just returned from my service obligation after interrupting my general surgery residency. I heard that a new resident from California had been admitted to our class, and, of course, it was Henry.

ABSTRACT: The separation of craniopagus conjoined twins is a very rare and complex challenge. As with many rare challenges, it presents initially as a deceptively simple problem requiring only the most basic clinical techniques. As in many reconstructive problems, this paradigm mandates that the neurosurgical team performs the separation with the plastic surgeons providing closure at the end of the separation. Historically, these approaches have included, as with the separation of many other types of conjoined twins, the use of tissue expansion before separation followed by separation surgery. In the best hands, at the most capable medical centers, the mortality reported in the literature for the past 50 years is greater than 50%. Craniofacial surgery frequently demands a coordinated effort between plastic surgery and neurosurgery and many other specializations; separating craniopagus twins takes this coordination to a stratospheric level. It is, however, this coordination that is of paramount importance. Success clearly requires an understanding of the complex interrelationship between the "separation" and the "reconstruction" and that decisions made for 1 aspect of the surgery will have a profound impact on another aspect of the surgery. The impact can be disastrous or, if planned well, can be advantageous.We were contacted to evaluate craniopagus conjoined male infant twins for separation. Radiographic studies suggested that the brains were separate, and their medical team suggested that they were "fit for separation." We reviewed the literature and reviewed our colleagues' experiences with similar cases around the world. It became clear that whether separation had been unsuccessful or successful, a variety of issues accompanied surgery as follows: (1) massive intraoperative hemorrhage, (2) cerebral edema, (3) venous infarcts, (4) swelling of flaps, and (5) dehiscence of repairs with cerebrospinal fluid (CSF) leak, meningitis, or brain exposure. Although the initial plan was to separate the twins in the same fashion as in previous cases (ie, single-stage separation surgery preceded by tissue expansion of the scalp), it was clear that this approach increases cerebral venous pressure during the separation component of surgery and therefore set up a cascade of events favoring failure rather than success. Wishing to favor success, we elected to design an open-ended multistaged separation to improve venous collateral circulation. We believe that this would improve venous drainage, prevent increased venous pressure, diminish cerebral edema, and favor the integrity of the dura and flap repair that would in turn lessen the risk of CSF leak. The stages would also allow the twins to recover from each stage before progressing to the next stage while continuing to receive nutritional support and physical therapy. Four major stages for 9 (1/2) months led to their successful separation. There has been no CSF leak or meningitis. To our knowledge, this technique has since been applied to 2 other sets of craniopagus with similar outcomes.A review of the pertinent literature, our rationale, and methodology are discussed in this article.

Encased in lacunae, osteocytes receive nutrition and biomechanical signals through the lacunocanalicular system. We have developed a novel flow-perfusion bioreactor designed to support lacunocanalicular fluid flow. We hypothesize that ex vivo fluid flow can maintain endochondral bone viability and, ultimately, serve as a novel model to study bone biology in vitro. Sprague-Dawley rat femurs were harvested, stripped of soft tissue, loaded into a custom-designed bioreactor and perfused with osteogenic culture medium. After 14 days of flow-perfusion or static culture, the bones were harvested, fixed, decalcified, embedded, sectioned and stained with haematoxylin and eosin. Fresh long bone samples were similarly processed for comparison. Osteocyte viability and function were also evaluated, using thiazolyl blue tetrazolium bromide (MTT), fluorospectrophotometric DNA quantification, alkaline phosphatase (ALP) colorimetric assay and fluorochrome labelling of mineralizing surfaces. All samples remained free of infection throughout the study period. After 14 days of flow perfusion, histological analysis showed normal-appearing bony architecture, with 72% of lacunae being osteocyte-filled compared with 93% in freshly harvested samples and only 36% in static samples. MTT staining and assay confirmed osteocyte viability in the flow-perfusion samples as well as in fresh samples. DNA quantification demonstrated DNA to be preserved in flow-perfused samples when compared with freshly harvested samples. ALP activity in flow-perfusion explants was upregulated compared with fresh and static samples. Fluorochrome-labelled mineralizing surfaces were seen throughout the explanted flow-perfused samples. This is the first demonstration that flow perfusion provides adequate chemotransportation to explanted murine endochondal bones

Introduction: The profunda artery perforator (PAP) flap is a new addition to our reconstructive armamentarium. In effort to better understand patient candidacy for the PAP flap we characterized the profunda artery perforators on preoperative imaging. Methods: A retrospective review was completed of 40 preoperative posterior thigh computed tomography angiographies and magnetic resonance angiographies by four plastic surgeons. The positioning of the patient, type of study, number of perforators, and size of perforators were documented. The location was documented on an x-y-axis. Perforator course and surrounding musculature was documented. Results: In 98.8% of posterior thighs suitable profunda artery perforators were identified. The average number and size of perforators was 3.3 and 1.9 mm. The most common perforator was medial (present in 85.6% of thighs); found near the adductor magnus at 3.8 cm from midline and 5.0 cm below the gluteal fold. The second most common perforator was lateral (present in 65.4% of thighs); found near the biceps femoris and vastus lateralis at 12.0 cm from midline and 5.0 cm below the gluteal fold. Nearly 48.3% were purely septocutaneous. And 51.7% had an intramuscular course (average length 5.7 cm). Preoperative imaging corresponded to suitable perforators at the time of dissection of all PAP flaps. Thirty five PAP flaps (18 patients) were performed with 100% flap survival. Conclusion: Analysis of preoperative posterior thigh imaging confirms our intraoperative findings that a considerable number of suitable posterior thigh profunda perforators are present, emerge from the fascia in a common pattern, and are of sufficient caliber to provide adequate flap perfusion and recipient vessel size match. (c) 2012 Wiley Periodicals, Inc. Microsurgery, 2012.