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Significance: Skin inevitably heals with the formation of a fibrotic scar. Patients affected by skin scarring suffer from long-term psychological and physical burdens. Recent Advances: Since the di...

Striae distensae are common disfiguring cutaneous lesions but lack effective treatments because of an incomplete understanding of their pathophysiology. Dermal fibroblasts likely play an important role. The authors investigate the cellular-molecular features distinguishing fibroblasts from human striae distensae and normal skin. The authors also develop a mouse model of striae distensae.Human striae distensae and normal skin samples were compared for tensile strength and histologic structure. Fibroblasts from striae distensae and normal skin were isolated by fluorescence-activated cell sorting for gene expression analysis. Immunofluorescence staining and fluorescence-activated cell sorting were used to confirm gene expression data at the protein level. A mouse model of striae distensae formation was created by administering corticosteroids and mechanically loading the dorsal skin.Human striae distensae exhibited reduced tensile strength, more disordered collagen fibers, and epidermal atrophy compared to human normal skin. There were 296 up-regulated genes in striae distensae fibroblasts, including the profibrotic lineage and surface marker CD26. Up-regulated genes were involved in profibrotic and mechanoresponsive signaling pathways (TGFβ and FAK-PI3-AKT-signaling). In contrast, 571 genes were down-regulated, including CD74 and genes of the AMPK pathway. Increased CD26 and decreased CD74 expression was confirmed by fluorescence-activated cell sorting and immunofluorescence. Similar cutaneous histologic and gene expression changes were induced in hypercortisolemic mice by mechanically loading the dorsal skin.Fibroblasts from human striae distensae exhibit increased profibrotic and decreased antifibrotic signaling. CD26 and CD74 are promising surface markers that may be targeted therapeutically. The authors' mouse model of striae distensae can be used as a platform to test the efficacy of potential therapeutic agents.Striae distensae are common disfiguring cutaneous lesions whose etiology remains elusive, which has hindered development of effective treatment strategies. Dermal fibroblasts likely play an important role. The authors sought to elucidate the key cellular-molecular pathways distinguishing fibroblasts in striae distensae from those in normal skin.

Children undergoing cleft palate repair present challenges to postoperative management due to several factors that can complicate recovery. Utilization of multimodal analgesic protocols can improve outcomes in this population. We report experience designing and implementing an enhanced recovery after surgery (ERAS) pathway for cleft palate repair to optimize postoperative recovery.The primary aim was to implement an ERAS pathway with70% bundle adherence to achieve a 30% reduction in postoperative opioid consumption within 12 months. Our secondary aims assessed intraoperative opioid consumption, length of stay, timeliness of oral intake, and respiratory recovery.A multidisciplinary team of perioperative providers developed an ERAS pathway for cleft palate patients. Key drivers included patient and provider education, formal pathway creation and implementation, multimodal pain therapy, and target-based care. Interventions included maxillary nerve blockade and enhanced intra- and postoperative medication regimens. Outcomes were displayed as statistical process control charts.Pathway compliance was 77.0%. Patients during the intervention period (n = 39) experienced a 49% reduction in postoperative opioid consumption (p .0001) relative to our historical cohort (n = 63), with a mean difference of -0.33 ± 0.11 mg/kg (95% CI -0.55 to -0.12 mg/kg). Intraoperative opioid consumption was reduced by 36% (p = .002), with a mean difference of -0.27 ± 0.09 mg/kg (95% CI -0.45 to -0.09 mg/kg). Additionally, patients in the intervention group had a 45% reduction in time to first oral intake (p = .02) relative to our historical cohort, with a mean difference of -3.81 ± 1.56 h (95% CI -6.9 to -0.70). There was no difference in PACU or hospital length of stay, but there was a significant reduction in variance of all secondary outcomes.Opioid reduction and improved timeliness of oral intake is possible with an ERAS protocol for cleft palate repair, but our protocol did not alter PACU or hospital length of stay.

BACKGROUND The purpose of this study was to evaluate the comparative incidence of obstructive sleep apnea following velopharyngeal insufficiency surgery in the United States. METHODS A retrospective analysis of cleft and noncleft pediatric patients who underwent velopharyngeal insufficiency surgery was performed using the IBM MarketScan Commercial Database. Patients were tracked longitudinally from 2007 to 2016 to evaluate the incidence of obstructive sleep apnea. Multivariable regression was used to evaluate predictors of postoperative obstructive sleep apnea and surgical revision. RESULTS A total of 1098 patients underwent a pharyngeal flap (61.0 percent), sphincter pharyngoplasty (22.2 percent), or palatal lengthening with or without island flaps (16.8 percent). Diagnoses were predominantly cleft lip and/or palate (52.8 percent) and congenital oropharyngeal anomalies (42.6 percent). Eighty patients (7.3 percent) developed obstructive sleep apnea at an average of 10.2 months postoperatively. Predictors of obstructive sleep apnea included older age (p = 0.014) and head and neck neoplasm (p = 0.011). The obstructive sleep apnea rate following sphincter pharyngoplasty was 11.1 percent, compared to 7.2 percent after pharyngeal flap surgery. Compared to sphincter pharyngoplasty, pharyngeal flap surgery was associated with a lower risk of further surgery (OR, 0.43; p = 0.010). Of patients with cleft lip and/or palate, 35 developed obstructive sleep apnea (6.0 percent) without a significant association with procedure type. CONCLUSIONS In this national claims database analysis of cleft and noncleft pediatric patients, the rate of obstructive sleep apnea following velopharyngeal insufficiency surgery was not significantly different for pharyngeal flap compared to sphincter pharyngoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE Therapeutic, III.

SUMMARY Striae distensae, or stretch marks, are common linear lesions of atrophic skin characterized histologically by epidermal atrophy, absent rete ridges, and alterations in connective tissue architecture. Hormonal excess, mechanical stress, and genetic predisposition are all associated with striae distensae, but their exact pathogenesis remains unknown. Despite a multitude of options, no single treatment has yet proven effective. In this article, the authors describe an up-to-date overview of striae distensae in terms of their etiology, pathophysiology, and therapeutic options. Further research is required to better elucidate their pathophysiology and to develop targeted effective treatments.

Objective: Mandibular distraction osteogenesis (MDO) is frequently performed to address airway obstruction in patients with Pierre Robin sequence (PRS), though more recently the technique of orthodontic airway plating (OAP) has gained traction. We aimed to evaluate OAP compared to MDO for airway obstruction in PRS. Design: A systematic literature search across PubMed, Embase, and Google Scholar identified all studies published in English, which involved MDO or any form of OAP as treatments for PRS. All relevant articles were reviewed in detail and reported on, adhering to PRISMA guidelines. Main Outcome Measures: Airway (tracheostomy avoidance, decannulation rate), feeding (full oral feeding tolerance). Results: Literature search identified 970 articles, of which 42 MDO studies and 9 OAP studies met criteria for review. A total of 1159 individuals were treated with MDO, and 322 individuals were treated with OAP. Primary outcomes appear similar for MDO and OAP at face value; however, this must be interpreted with different pretreatment contexts in mind. Conclusions: Orthodontic airway plating may be considered for airway obstruction in PRS, as some airway-related and feeding-related outcomes appear similar with MDO, per existing evidence in the literature. However, since PRS severity differed between studies, OAP cannot be uniformly considered a replacement for MDO. Further research is required to more comprehensively assess these treatment modalities inclusive of metrics that allow for direct comparison.

Background Aesthetic outcomes of unilateral cleft lip repairs have important psychosocial implications for patients who are heavily influenced by social perceptions. Online crowdsourcing offers the unique potential to efficiently recruit large numbers of laypeople to assess public perception. The aim of this study was to use the online crowdsourcing platform Mechanical Turk to compare the postoperative outcomes of Fisher, Millard, and Mohler cleft lip repair techniques. Methods Two hundred fifty-four participants were recruited through Mechanical Turk to evaluate 29 cropped and deidentified photographs of children, 8 photographs were controls without cleft lips and 21 were children with unilateral cleft lips who had undergone Fisher, Millard, or Mohler repairs (7 in each group). Respondents were asked whether a scar was present, whether they would be personally satisfied with the surgical result and used a Likert scale from 1 to 5 to rate overall appearance, scar severity, and nasal symmetry. Results Fewer respondents reported that a scar was present when assessing postoperative photographs of Fisher repairs (70.3 ± 8.6%) compared with Millard (92.0 ± 1.5%) or Mohler (88.8 ± 3.1%) repairs. Average rating of scar severity was also lower for Fisher (1.9) compared with Millard (2.6) or Mohler (2.6) repairs. Average ratings of nose symmetry, general appearance, and satisfaction with operative result were not statistically significantly different between the repair groups. Conclusions This study demonstrates the potential of online crowdsourcing to assess public perception of plastic surgery outcomes. The Mechanical Turk platform offers a reduction in selection bias, ease of study design, and enhanced efficiency of large-scale participant recruitment. Results indicate that the Fisher repair led to the most favored aesthetic outcomes compared with the Millard and Mohler techniques, particularly with regard to scar severity. Crowdsourcing is a powerful tool to assess layperson perception of plastic surgery outcomes and can be used to better guide surgical decision-making.

Objective Assess whether facial trauma wound care and antibiotic use recommendations are guided by evidence-based practice (EBP) or practice patterns, and investigate strategies to improve EBP adoption among surgical trainees. Design We conducted a survey of all trainees who manage facial trauma (general surgery, emergency medicine, plastic surgery, otolaryngology) to assess clinical knowledge and sources of treatment recommendations. Clinical questions were based on Oxford Center for Evidence-Based Medicine Level 1 or 2 evidence. We measured internal validity of questions using Cronbach's α. Results were weight-adjusted for nonresponse and then analyzed using Welch t test and descriptive statistics. Study Setting Stanford Hospital and Clinics, a Level I trauma center. Results Response rate was 50.3% overall (78/155). For recommendations on facial trauma wound and antibiotic use, nonspecialty junior residents most frequently relied on their own senior or specialty residents (79.1%); nonspecialty senior residents relied on specialty residents (67.9%). Specialty junior residents most often relied on their own senior residents (51.0%), the majority of whom made recommendations based on their own knowledge (73.2%). Questions assessing EBP knowledge had Cronbach's α of 0.98; response accuracy was similar between specialty and nonspecialty residents (54.6% vs 55.5%, p = 0.96). When provided recommendations that conflict with EBP, both nonspecialty and specialty residents more frequently followed recommendations rather than EBP; junior residents reported doing so to avoid conflict with superiors. Total 92.6% of surveyed residents felt cross-departmental EBP guidelines would improve patient care. Conclusions Facial trauma wound care and antibiotic recommendations disseminate down seniority and from craniofacial specialty to nonspecialty residents, yet knowledge of EBP among senior specialty and nonspecialty residents was weak. EBP may be difficult to adopt in the absence of consensus society guidelines. To address this gap, we published a review of EBP for facial trauma and plan to update our trauma manual with cross-departmental guidelines to facilitate EBP adoption among trainees.

BACKGROUND Cell therapy with mesenchymal stromal cells is a promising strategy for tissue repair. Restoration of blood flow to ischemic tissues is a key step in wound repair, and mesenchymal stromal cells have been shown to be proangiogenic. Angiogenesis is critically regulated by the hypoxia-inducible factor (HIF) superfamily, consisting of transcription factors targeted for degradation by prolyl hydroxylase domain (PHD)-2. The aim of this study was to enhance the proangiogenic capability of mesenchymal stromal cells and to use these modified cells to promote wound healing. METHODS Mesenchymal stromal cells harvested from mouse bone marrow were transduced with short hairpin RNA (shRNA) against PHD-2; control cells were transduced with scrambled shRNA (shScramble) construct. Gene expression quantification, human umbilical vein endothelial cell tube formation assays, and wound healing assays were used to assess the effect of PHD knockdown mesenchymal stromal cells on wound healing dynamics. RESULTS PHD-2 knockdown mesenchymal stromal cells overexpressed HIF-1α and multiple angiogenic factors compared to control (p < 0.05). Human umbilical vein endothelial cells treated with conditioned medium from PHD-2 knockdown mesenchymal stromal cells exhibited increased formation of capillary-like structures and enhanced migration compared with human umbilical vein endothelial cells treated with conditioned medium from shScramble-transduced mesenchymal stromal cells (p < 0.05). Wounds treated with PHD-2 knockdown mesenchymal stromal cells healed at a significantly accelerated rate compared with wounds treated with shScramble mesenchymal stromal cells (p < 0.05). Histologic studies revealed increased blood vessel density and increased cellularity in the wounds treated with PHD-2 knockdown mesenchymal stromal cells (p < 0.05). CONCLUSIONS Silencing PHD-2 in mesenchymal stromal cells augments their proangiogenic potential in wound healing therapy. This effect appears to be mediated by overexpression of HIF family transcription factors and up-regulation of multiple downstream angiogenic factors.

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) patients have mutations in the COL7A1 gene and thus lack functional type VII collagen (C7) protein; they have marked skin fragility and blistering. This single-center phase 1/2a open-label study evaluated the long-term efficacy, safety, and patient-reported outcomes in RDEB patients treated with gene-corrected autologous cell therapy. METHODS: Autologous keratinocytes were isolated from participant skin biopsies. Epidermal sheets were prepared from cells transduced with a retrovirus carrying the full-length human COL7A1 gene. These gene-corrected autologous epidermal sheets measured 5 × 7 cm (35 cm(2)) and were transplanted onto 6 wound sites in each of 7 adult participants (n = 42 sites total) from 2013 to 2017. Participants were followed for 2 to 5 years. RESULTS: No participants experienced any serious related adverse events. Wound healing of 50% or greater by Investigator Global Assessment was present in 95% (36 of 38) of treated wounds versus 0% (0 of 6) of untreated control wounds at 6 months (P < 0.0001). At year 1, 68% (26 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.025). At year 2, 71% (27 of 38) of treated wounds had 50% or greater healing compared with 17% (1 of 6) of control wounds (P = 0.019). CONCLUSION: C7 expression persisted up to 2 years after treatment in 2 participants. Treated wounds with 50% or greater healing demonstrated improvement in patient-reported pain, itch, and wound durability. This study provides additional data to support the clinically meaningful benefit of treating chronic RDEB wounds with ex vivo, C7 gene–corrected autologous cell therapy. This approach was safe and promoted wound healing that was associated with improved patient-reported outcomes. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01263379. FUNDING: Epidermolysis Bullosa Research Partnership, Epidermolysis Bullosa Medical Research Foundation, NIH R01 AR055914, Office of Research and Development at the Palo Alto Veteran’s Affairs Medical Center, and the Dermatology Foundation.

Pediatric facial fracture management is often complex and demanding. The structure and topography of the pediatric craniofacial skeleton are profoundly different from the mature skull. Consequently, the pediatric facial skeleton responds differently to traumatic force. Although the incidence of pediatric facial trauma is higher than in the adult population, the incidence of facial fracture is significantly lower. The management in younger patients is often more conservative because of potential growth impairment. As the facial skeleton matures, more conventional surgical approaches become appropriate. This review provides an understanding of the unique elements of facial fracture management in the pediatric population.

From the moment we are born, every injury to the skin has the potential to form a scar, many of which can impair form and/or function. As such, scar management constitutes a billion-dollar industry. However, effectively promoting scarless wound healing remains an elusive goal. The complex interactions of wound healing contribute to our inability to recapitulate scarless wound repair as it occurs in nature, such as in fetal skin and the oral mucosa. However, many new advances have occurred in recent years, some of which have translated scientific findings from bench to bedside. In vivo lineage tracing has helped establish a variety of novel cellular culprits that may act as key drivers of the fibrotic response. These newly characterized cell populations present further targets for therapeutic intervention, some of which have previously demonstrated promising results in animal models. Here, we discuss several recent studies that identify exciting approaches for diminishing scar formation. Particular attention will also be paid to the canonical Wnt/β-catenin signaling pathway, which plays an important role in both embryogenesis and tissue repair. New insights into the differential effects of Wnt signaling on heterogeneous fibroblast and keratinocyte populations within the skin further demonstrate methods by which wound healing can be re-directed to a more fetal scarless phenotype. Graphical abstract Recent approaches to reducing scar formation. Representation showing novel scientific approaches for decreasing scar formation, including the targeting of pro-fibrotic cell populations based on surface molecule expression (e.g. DPP4(+) fibroblasts, ADAM12(+) pericytes). Modulation of cellular mechanotransduction pathways are another means to reduce scar formation, both at the molecular level or, macroscopically with dressings designed to offload tension, at cutaneous wound sites (ADAM12 a disintegrin and metalloprotease 12, DPP4 dipeptidyl peptidase-4, FAK focal adhesion kinase).

A new group of blood-derived CD34+ progenitor cells (BDPCs) with the ability to expand and differentiate into functional hepatocyte-like cells and promote liver regeneration is reported. With their ease of access, application through the peripheral blood, and the capability of rapid expansion and hepatic differentiation, BDPCs have great potential as a cell-based therapy for liver disease., The low availability of functional hepatocytes has been an unmet demand for basic scientific research, new drug development, and cell-based clinical applications for decades. Because of the inability to expand hepatocytes in vitro, alternative sources of hepatocytes are a focus of liver regenerative medicine. We report a new group of blood-derived CD34+ progenitor cells (BDPCs) that have the ability to expand and differentiate into functional hepatocyte-like cells and promote liver regeneration. BDPCs were obtained from the peripheral blood of an adult mouse with expression of surface markers CD34, CD45, Sca-1, c-kit, and Thy1.1. BDPCs can proliferate in vitro and differentiate into hepatocyte-like cells expressing hepatocyte markers, including CK8, CK18, CK19, α-fetoprotein, integrin-β1, and A6. The differentiated BDPCs (dBDPCs) also display liver-specific functional activities, such as glycogen storage, urea production, and albumin secretion. dBDPCs have cytochrome P450 activity and express specific hepatic transcription factors, such as hepatic nuclear factor 1α. To demonstrate liver regenerative activity, dBDPCs were injected into mice with severe acute liver damage caused by a high-dose injection of carbon tetrachloride (CCl4). dBDPC treatment rescued the mice from severe acute liver injury, increased survival, and induced liver regeneration. Because of their ease of access and application through peripheral blood and their capability of rapid expansion and hepatic differentiation, BDPCs have great potential as a cell-based therapy for liver disease. Significance Hematopoietic stem/progenitor cell expansion and tissue-specific differentiation in vitro are challenges in regenerative medicine, although stem cell therapy has raised hope for the treatment of liver diseases by overcoming the scarcity of hepatocytes. This study identified and characterized a group of blood-derived progenitor cells (BDPCs) from the peripheral blood of an adult mouse. The CD34+ progenitor-dominant BDPCs were rapidly expanded and hepatically differentiated into functional hepatocyte-like cells with our established coculture system. BDPC treatment increased animal survival and produced full regeneration in a severe liver injury mouse model caused by CCl4. BDPCs could have potential for liver cell therapies.

Fetal cutaneous wounds have the unique ability to completely regenerate wounded skin and heal without scarring. However, adult cutaneous wounds heal via a fibroproliferative response which results in the formation of a scar. Understanding the mechanism(s) of scarless wound healing leads to enormous clinical potential in facilitating an environment conducive to scarless healing in adult cutaneous wounds. This article reviews the embryonic development of the skin and outlines the structural and functional differences in adult and fetal wound healing phenotypes. A review of current developments made towards applying this clinical knowledge to promote scarless healing in adult wounds is addressed.

Cranial bone repair is one of the oldest neurosurgical practices. Reconstructing the natural contours of the skull has challenged the ingenuity of surgeons from antiquity to the present day. Given the continuous improvement of neurosurgical and emergency care over the past century, more patients survive such head injuries, thus necessitating more than ever before a simple, safe, and durable means of correcting skull defects. In response, numerous techniques and materials have been devised as the art of cranioplasty has progressed. Although the goals of cranioplasty remain the same, the evolution of techniques and diversity of materials used serves as testimony to the complexity of this task. This paper highlights the evolution of these materials and techniques, with a particular focus on the implications for managing pediatric calvarial repair and emerging trends within the field.

Over 100 million patients acquire scars in the industrialized world each year, primarily as a result of elective operations. Although undefined, the global incidence of scarring is even larger, extending to significant numbers of burn and other trauma-related wounds. Scars have the potential to exert a profound psychological and physical impact on the individual. Beyond aesthetic considerations and potential disfigurement, scarring can result in restriction of movement and reduced quality of life. The formation of a scar following skin injury is a consequence of wound healing occurring through reparative rather than regenerative mechanisms. In this article, the authors review the basic stages of wound healing; differences between adult and fetal wound healing; various mechanical, genetic, and pharmacologic strategies to reduce scarring; and the biology of skin stem/progenitor cells that may hold the key to scarless regeneration.

Chondromyxoid fibroma is a rare bony tumor that usually presents in the lower extremities of middle-aged adults. Involvement of the craniofacial skeleton is extremely rare. We present the unique case of an adolescent boy with a chondromyxoid fibroma of the mandible. The chondromyxoid fibroma in this patient recurred after initial treatment with curettage. We treated the recurrence with resection of the involved mandible and immediate reconstruction using a vascularized musculo-osseus seventh rib flap (“Eve procedure”). Despite complex reconstruction in adolescents due to skeletal immaturity, the rib flap has successfully grown with the patient up to 3 years postoperatively. Therefore, we believe the musculo-osseus rib flap is a feasible solution for complex ramus and condyle reconstruction of the growing mandible in the adolescent patient.

Invasive cancers, major injuries, and infection can cause bone defects that are too large to be reconstructed with preexisting bone from the patient's own body. The ability to grow bone de novo using a patient's own cells would allow bony defects to be filled with adequate tissue without the morbidity of harvesting native bone. There is interest in the use of adipose-derived stromal cells (ASCs) as a source for tissue engineering because these are obtained from an abundant source: the patient's own adipose tissue. However, ASCs are a heterogeneous population and some subpopulations may be more effective in this application than others. Isolation of the most osteogenic population of ASCs could improve the efficiency and effectiveness of a bone engineering process. In this protocol, ASCs are obtained from subcutaneous fat tissue from a human donor. The subpopulation of ASCs expressing the marker BMPR-IB is isolated using FACS. These cells are then applied to an in vivo calvarial defect healing assay and are found to have improved osteogenic regenerative potential compared with unsorted cells.

Wound healing is a highly evolved defense mechanism against infection and further injury. It is a complex process involving multiple cell types and biological pathways. Mammalian adult cutaneous wound healing is mediated by a fibroproliferative response leading to scar formation. In contrast, early to mid-gestational fetal cutaneous wound healing is more akin to regeneration and occurs without scar formation. This early observation has led to extensive research seeking to unlock the mechanism underlying fetal scarless regenerative repair. Building upon recent advances in biomaterials and stem cell applications, tissue engineering approaches are working towards a recapitulation of this phenomenon. In this review, we describe the elements that distinguish fetal scarless and adult scarring wound healing, and discuss current trends in tissue engineering aimed at achieving scarless tissue regeneration.

Scar formation is a major medical problem that can have devastating consequences for patients. The adverse physiological and psychological effects of scars are broad, and there are currently no reliable treatments to prevent scarring. In contrast to adult wounds, early gestation fetal skin wounds repair rapidly and in the absence of scar formation. Despite extensive investigation, the exact mechanisms of scarless fetal wound healing remain largely unknown. For some time, it has been known that significant differences exist among the extracellular matrix, inflammatory response, cellular mediators, and gene expression profiles of fetal and postnatal wounds. These differences may have important implications in scarless wound repair.

Postnatal tissue-specific stem/progenitor cells hold great promise to enhance repair of damaged tissues. Many of these cells are retrieved from bone marrow or adipose tissue via invasive procedures. Peripheral blood is an ideal alternative source for the stem/progenitor cells because of its ease of retrieval. We present a coculture system that routinely produces a group of cells from adult peripheral blood. Treatment with these cells enhanced healing of critical-size bone defects in the mouse calvarium, a proof of principle that peripheral blood-derived cells can be used to heal bone defects. From these cells, we isolated a subset of CD45− cells with a fibroblastic morphology. The CD45− cells were responsible for most of the differentiation-induced calcification activity and were most likely responsible for the enhanced healing process. These CD45− fibroblastic cells are plastic-adherent and exhibit a surface marker profile negative for CD34, CD19, CD11b, lineage, and c-kit and positive for stem cell antigen 1, CD73, CD44, CD90.1, CD29, CD105, CD106, and CD140α. Furthermore, these cells exhibited osteogenesis, chondrogenesis, and adipogenesis capabilities. The CD45− fibroblastic cells are the first peripheral blood-derived cells that fulfill the criteria of mesenchymal stem cells as defined by the International Society for Cellular Therapy. We have named these cells “blood-derived mesenchymal stem cells.”

Wound healing can be characterized as underhealing, as in the setting of chronic wounds, or overhealing, occurring with hypertrophic scar formation after burn injury. Topical therapies targeting specific biochemical and molecular pathways represent a promising avenue for improving and, in some cases normalizing, the healing process.A brief overview of both normal and pathological wound healing has been provided, along with a review of the current clinical guidelines and treatment modalities for chronic wounds, burn wounds and scar formation. Next, the major avenues for wound healing drugs, along with drugs currently in development, are discussed. Finally, potential challenges to further drug development, and future research directions are discussed.The large body of research concerning wound healing pathophysiology has provided multiple targets for topical therapies. Growth factor therapies with the ability to be targeted for localized release in the wound microenvironment are most promising, particularly when they modulate processes in the proliferative phase of wound healing.

Early in utero, but not in postnatal life, cutaneous wounds undergo regeneration and heal without formation of a scar. Scarless fetal wound healing occurs across species but is age dependent. The transition from a scarless to scarring phenotype occurs in the third trimester of pregnancy in humans and around embryonic day 18 (E18) in mice. However, this varies with the size of the wound with larger defects generating a scar at an earlier gestational age. The emergence of lineage tracing and other genetic tools in the mouse has opened promising new avenues for investigation of fetal scarless wound healing. However, given the inherently high rates of morbidity and premature uterine contraction associated with fetal surgery, investigations of fetal scarless wound healing in vivo require a precise and reproducible surgical model. Here we detail a reliable model of fetal scarless wound healing in the dorsum of E16.5 (scarless) and E18.5 (scarring) mouse embryos.

Purpose Benign tumors of the brow and forehead are commonly managed by pediatric general surgeons by excision through an overlying incision. Cosmetic results in children can be suboptimal. Plastic surgeons have used endoscopic brow-lift techniques for the removal of these lesions. We review our experience after adopting this endoscopic technique in a pediatric general surgery practice. Methods We conducted a retrospective chart review of 9 consecutive outpatient procedures (5 girls and 4 boys; age range, 5 months to 12 years) between March and October 2005. Seven patients had lesions located on the lateral brow (left, n = 4; right, n = 3), 1 patient had a lesion on the left mid forehead, and 1 patient had a nasoglabellar cyst. All procedures were performed using endoscopic brow-lift equipment through a single small scalp incision 2 cm posterior to the hairline. Outcome measures included need for conversion, operative time, cosmetic outcome, and complications. Results All lesions (6 dermoid cysts and 3 pilomatrixomas) were successfully excised endoscopically. The mean operative time was 56 minutes (range, 22-90 minutes). There was no intraoperative or postoperative complication. All families were pleased with the cosmetic outcomes. Conclusion This case report shows that endoscopic excision of forehead masses is a safe and efficacious procedure in the hands of pediatric general surgeons.

UNLABELLED Scar cosmesis is one of the proposed benefits of mini-incision total hip replacement as opposed to standard-incision procedures; however, there has been no scientific proof of this clinical outcome. The cosmetic appearances of healed incisions of 34 primary total hip replacement procedures done by one surgeon using either a mini-incision (20 procedures) or a standard-length incision (14 procedures) were compared at an average of 2 years postoperatively. Each scar's appearance was graded independently by two plastic surgeons using a standardized rating system. Patients answered a questionnaire regarding their subjective assessment of their scar. The blinded observers found that more mini-scars (six of 20) were rated poor than standard scars (one of 14) and that more standard-incision patients had scars that were rated good. More mini-incision patients (two of 20 versus zero of 14) had wound-healing problems. All the patients thought that their hip scar was acceptable in appearance, but 30 of 31 patients rated the relief of pain and total hip replacement longevity as higher priorities than scar cosmesis. The cosmesis of mini-incision total hip replacement scars may be inferior to standard-incision scars because of skin and soft tissue damage produced by high retractor pressures needed for exposure using a limited skin incision. LEVEL OF EVIDENCE Therapeutic study, Level II-2 (prospective comparative study). See the Guidelines for Authors for a complete description of levels of evidence.

Surgical intervention is currently performed on highly selected fetuses with anatomical deformities that have a high mortality or severe morbidity when treated postnatally. In the future, in utero surgical intervention for non-life-threatening disease may become possible as fetal surgery becomes safer for the mother and fetus. Fetal cleft repair is an attractive intervention for plastic surgeons because it affords the potential to provide a scarless repair and correct the primary deformity. Furthermore, scarless fetal lip and palate repairs may prevent the ripple effect of postnatal scarring with its resultant secondary dentoalveolar and midface growth deformities. These potential benefits can dramatically reduce the number of postnatal reconstructive procedures in children with facial clefts. The rationale for a prenatal treatment approach to the patient with cleft lip/palate and the experimental evidence to support in utero intervention are discussed in this article.

We describe a novel rat cDNA named keratinocyte proline-rich protein (KPRP) isolated by RNA differential display during skin development. We determine that KPRP is expressed in stratified squamous epithelium, and its approximately 2.8-kb cDNA encodes a 699-amino acid protein with high proline content (19%). KPRP is an insoluble protein, similar to most epidermal terminal differentiation-associated proteins. Immunoblot of the protein lysate from keratinocytes, using strong reducing conditions, demonstrates two KPRP bands of approximately 76 and 55 kDa size. KPRP is expressed in stratified squamous epithelia of skin, tongue, and esophagus. The initiation of KPRP expression in fetal rat skin at E17, E18, E19, E20, and E21 was analyzed by reverse transcription-PCR. Fetal skin at E19 and later expresses KPRP. In situ hybridization of skin from E18, E19, and 4-day-old neonatal rats demonstrates that interfollicular and follicular keratinocytes express KPRP. Anti-KPRP antibody demonstrates KPRP protein localizes to all layers of stratified epithelia in skin, tongue, and esophagus. In cultured dermal keratinocytes, KPRP is diffusely distributed throughout the cytoplasm with denser staining adjacent to the nuclear and plasma membranes. Additionally, immunoreactive intracellular granules are observed during keratinocyte detachment from their plastic substrate. Rat KPRP has 89% homology to a mouse genomic DNA sequence and 56% homology to a human hypothetical protein. We conclude that KPRP may be a new epidermal terminal differentiation-related protein expressed in stratified squamous epithelia. KPRP is expressed by fetal dermal keratinocytes during late gestation and is a new marker of maturing epidermis during fetal skin development.

Malignant ventricular tachycardia occurs most frequently in patients with coronary artery disease who have had a previous myocardial infarction and in whom a ventricular aneurysm subsequently develops in the scarred section of myocardium. Ventricular tachycardia in the presence of normal coronary arteries and a left ventricular aneurysm is unusual and can be refractory to medical therapy. We retrospectively reviewed our experience of 10 patients treated at our institution from 1983 to 1993. Age ranged from 22 to 76 years, and all patients presented with sustained ventricular tachycardia. All patients underwent complete electrophysiologic testing. Cardiac catheterization was performed in 9 patients, and each had normal coronary artery anatomy without evidence of significant fixed lesions. A left ventricular aneurysm, diagnosed by either echocardiography, thoracic cine computed tomography or magnetic resonance imaging, or ventricular angiography was present in all patients. Ventricular tachycardia could not be suppressed pharmacologically in 7 of 10 patients using multiple agents including procainamide, quinidine, flecanide, tocainide, propaferone, and amiodarone. Six patients were treated surgically by intraoperative electrophysiologic mapping, endocardial resection of foci, and left ventricular aneurysmectomy. An implantable cardiac defibrillator device was implanted in 2 patients. One patient died on the second postoperative day after simultaneous mapping-guided aneurysmectomy and implantable cardioverter defibrillator placement. There was one late postoperative death. All other surgically treated patients had postoperative electrophysiologic studies demonstrating no inducible ventricular tachycardia, and these patients remain without antiarrhythmic therapy in follow-up extending from 29 to 86 months (mean, 56 months). Surgical pathologic examination showed nonspecific myocardial scarring and fibrosis in the aneurysm walls, which ranged in size from small apical to large broad-based basilar aneurysms with a cavity volume equal to that of the left ventricle. Our experience supports surgical therapy for medically refractory arrhythmogenic left ventricular aneurysms unrelated to coronary artery disease.

Scar formation, a physiologic process in adult wound healing, can have devastating effects for patients; a multitude of pathologic outcomes, affecting all organ systems, stems from an amplification of this process. In contrast to adult wound repair, the early-gestation fetal skin wound heals without scar formation, a phenomenon that appears to be intrinsic to fetal skin. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to this scarless repair. Despite the great increase in knowledge gained over the past decades, the precise mechanisms regulating scarless fetal healing remain unknown. Herein, we describe the current proposed mechanisms underlying fetal scarless wound healing in an effort to recapitulate the fetal phenotype in the postnatal environment. Birth Defects Research (Part C) 96:237–247, 2012. © 2012 Wiley Periodicals, Inc.

Bioabsorbable fixation systems have been widely employed in pediatric patients for cranial reconstruction, obviating the complications of hardware migration and imaging artifact occurring with metallic implants. Recent concern over complications unique to bioabsorbable materials, such as inflammatory reaction and incomplete resorption, necessitates additional conclusive studies to further validate their use in pediatric neurosurgery and craniofacial surgery. Likewise, long-term follow-up in this clinical cohort has not previously been described.We included consecutive pediatric patients under the age of 2, from Lucile Packard Children's Hospital, who underwent cranial vault reconstruction with the use of a bioabsorbable fixation system between 2003 and 2010. Hospital records were queried for patient characteristics, intraoperative data, and postoperative complications.Ninety-five patients with the following preoperative pathologies were analyzed: craniosynostosis (87), cloverleaf skull (5), frontonasal dysplasia (1), and frontonasal encephalocele (2). Median age was 6 months (range 1-24 months). Average case duration was 204 minutes (range 40-392 min), with median of 154 mL blood loss (range 30-500 mL). Ninety-three percent of patients had 1-4 plates implanted with 48% receiving three plates. The median number of screws used was 59 (range 0-130). The median length of hospital stay was 4 days (range 2-127 days) with an average follow-up of 22 months (five postoperative visits). The complications related to hardware implantation included swelling (1%) and broken hardware (1%), the latter of which required reoperation.The bioabsorbable fixation systems for cranial vault reconstruction in children less than 2 years of age is safe with tolerable morbidity rates.

Optimal fetal management during and after fetal surgery has been limited by an inability to reliably monitor the fetal heart rate and temperature, and by a lack of access to the fetal circulation. In order to solve these problems, we used early third trimester fetal sheep to develop: (1) an implantable radiotelemetry device that transmits the fetal electrocardiogram and temperature, and (2) an intraosseous access technique. A miniaturized radiotelemeter was implanted subcutaneously in the axilla of four fetal sheep. Safe implantation of the radiotelemeter was technically feasible and the device reliably recorded the fetal electrocardiogram and temperature both intraoperatively and postoperatively. Although many possible routes for access to the fetal circulation have been tried experimentally and clinically for both resuscitation and blood sampling, none have proven satisfactory. We assessed the use of intraosseous access in fetal sheep (n = 6) for both infusion and blood sampling. Access with an intraosseous needle was obtained in both sheep fetuses and human fetal cadavers. Blood gas values (pH, PCO 2 , and PO 2 ) obtained from the medullary cavity of fetal sheep accurately reflected peripheral venous values. Resuscitation drugs reached the fetal circulation via the intraosseous route: sodium bicarbonate elevated venous bicarbonate levels from 28.4 ± 1.7 to 31.8 ± 2.1 mEq/dL ( P P P P ≤ .01). Application of the implantable radiotelemeter and intraosseous access techniques may enhance fetal surgery safety by improving fetal monitoring and permitting reliable access to the fetal circulation.

Emergency thoracotomy is a standard procedure in the management of cardiac arrest in patients sustaining severe trauma. We examined the records of 463 moribund trauma patients treated at our institution from 1980 to 1990 to refine indications for emergency thoracotomy. Patients underwent thoracotomy either in the emergency department (ED) (n = 424) or in the operating room (OR) (n = 39) as a component of continuing resuscitation after hospital arrival. The survival rate was 13% (61 of 463) overall, 2% (3 of 193) for blunt, 22% (58 of 269) for all penetrating, 8% (10 of 131) for gunshot, 34% (48 of 141) for stab-wound patients, and 54% (21 of 39) for patients who underwent emergency thoracotomy in the OR. Survival correlated with the physiologic status of patients both on initial evaluation in the field by paramedics and on arrival at the ED. Patients with penetrating trauma and in profound shock (BP less than 60 mm Hg) or mild shock (BP 60-90 mm Hg) with subsequent cardiac arrest had survival rates of 64% (27 of 42) and 56% (30 of 54), respectively. None of the patients with absent signs of life, defined as full cardiopulmonary arrest with absent reflexes (n = 215), on initial assessment by paramedics in the field, survived. We conclude that (1) no emergency thoracotomy should be performed if no signs of life are present on the initial prehospital field assessment; (2) emergency thoracotomy is an indicated procedure in most patients sustaining penetrating trauma; (3) blunt traumatic cardiac arrest is a relative contraindication to emergency thoracotomy.

The developing fetus has the ability to heal wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix (ECM) architecture, strength, and function. In contrast, adult wounds heal with fibrosis and scar. Scar tissue remains weaker than normal skin with an altered ECM composition. Despite extensive investigation, the mechanism of fetal wound healing remains largely unknown. We do know that early in gestation, fetal skin is developing at a rapid pace and the ECM is a loose network facilitating cellular migration. Wounding in this unique environment triggers a complex cascade of tightly controlled events culminating in a scarless wound phenotype of fine reticular collagen and abundant hyaluronic acid. Comparison between postnatal and fetal wound healing has revealed differences in inflammatory response, cellular mediators, cytokines, growth factors, and ECM modulators. Investigation into cell signaling pathways and transcription factors has demonstrated differences in secondary messenger phosphorylation patterns and homeobox gene expression. Further research may reveal novel genes essential to scarless repair that can be manipulated in the adult wound and thus ameliorate scar.

Normal craniofacial development is contingent upon coordinated growth between the brain and overlying calvaria. Craniosynostosis, the premature fusion of one or more cranial sutures, perturbs this natural framework, resulting in dramatic dysmorphology of the skull and face along with a multitude of associated functional abnormalities. Traditional approaches to the treatment of craniosynostosis have employed complex surgical remodeling of the skull vault and facial deformities all aimed at increasing the amount of intracranial volume and restoring a more normal craniofacial appearance. Significant morbidity and mortality, however, have plagued these procedures, driving dramatic evolution in our approach towards the treatment of pathologically fused sutures. Recent clinical and genetic studies have identified multiple forms of human craniosynostosis, each associated with mutations within various cytokine signaling pathways. Knowledge garnered from these investigations bear promise for the future development of alternative strategies to enhance or perhaps even replace contemporary approaches for the treatment of craniosynostosis.

Mandibular distraction has proven to be a valuable tool for lengthening the hypoplastic mandible and relieving airway obstruction in infants. Numerous devices have been developed to achieve the desired mandibular lengthening. Complications including poor vector control, need to mold regenerate, facial scarring, external pin loosening, and bulky hardware have been associated with previous devices. In an attempt to circumvent some of these problems, the senior author developed an internal curvilinear device (Osteomed Corporation, Dallas, TX), which is applicable to the infant mandible. The aim of this paper is to describe the use of this distractor as well as its indications and outcomes. Twelve micrognathic infants (ages range from 9 days to 8 months) who underwent mandibular distraction between March 2005-May 2006 at Lucile Packard Children's Hospital were included in the study. Preoperative workup included an evaluation by a multidisciplinary team including a pediatric otolaryngologist, neonatal intensivist, pediatric pulmonologist, occupational therapist, and craniofacial surgeon. Pre and postoperative maxillomandibular discrepancy, sleep study, feeding evaluation, and three-dimensional computerized tomography scans were compared. All patients tolerated the distraction process well to completion without postoperative complication, except for one patient who had temporary facial nerve weakness, which resolved in 2 months. All patients with obstructive apnea had the obstructive component improved. The last six patients had pre and postoperative polysomnograms to document the improvement. Two patients with neurologic impairment had persistent central apnea. One nonsyndromic patient with inability to feed and feeding-related airway obstruction was taking complete oral feeds 2 weeks after distraction. Mandibular distraction with an internal curvilinear device is effective at relieving airway obstruction in micrognathic infants, while avoiding some previously reported complications.

Wounds in fetal skin heal without scar, however the mechanism is unknown. We identified a novel group of E-cadherin positive cells in the blood of fetal and adult mice and named them "Dot cells". The percentage of Dot cells in E16.5 fetal mice blood is more than twenty times higher compared to adult blood. Dot cells also express integrin beta1, CD184, CD34, CD13low and Sca1low, but not CD45, CD44, and CD117. Dot cells have a tiny dot shape between 1 and 7 microm diameters with fast proliferation in vitro. Most of the Dot cells remain positive for E-cadherin and integrin beta1 after one month in culture. Transplantation of Dot cells to adult mice heals skin wounds with less scar due to reduced smooth muscle actin and collagen expression in the repair tissue. Tracking GFP-positive Dot cells demonstrates that Dot cells migrate to wounds and differentiate into dermal cells, which also express strongly to FGF-2, and later lose their GFP expression. Our results indicate that Dot cells are a group of previously unidentified cells that have strong wound healing effect. The mechanism of scarless wound healing in fetal skin is due to the presence of a large number of Dot cells.

The developing fetus has the remarkable ability to heal dermal skin wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix architecture, strength, and function. The biology responsible for scarless wound healing in skin is a paradigm for ideal tissue repair. This regenerative capacity is lost in late gestation when fetal wounds heal with fibrosis and scar. Early in gestation, fetal skin is developing at a rapid pace in a unique environment. Investigation of normal skin embryogenesis and comparison between early scarless and late scarring fetal wounds has revealed distinct differences in inflammatory response, cellular mediators, wound contraction, cytokines, growth factors, and extracellular matrix modulators. The knowledge gained from comparative observational studies has served as a base for experimental interventions in animal models to induce or ameliorate scar. Although much progress has been made over the past decade, the mechanism of fetal wound healing remains largely unknown and attempts to mimic the scarless wound phenotype have not been completely successful. Identification of more key genes involved in skin regeneration may have implications in adult skin wounds and repair in other organ systems.

The use of stem cells for cell-based tissue-engineering strategies represents a promising alternative for the repair of cartilaginous defects. The multilineage potential of a population of putative mesodermal stem cells obtained from human lipoaspirates, termed processed lipoaspirate cells, was previously characterized. The chondrogenic potential of those cells was confirmed with a combination of histological and molecular approaches. Processed lipoaspirate cells under high-density micromass culture conditions, supplemented with transforming growth factor-beta1, insulin, transferrin, and ascorbic acid, formed well-defined nodules within 48 hours of induction and expressed the cartilaginous markers collagen type II, chondroitin-4-sulfate, and keratan sulfate. Reverse transcription polymerase chain reaction analysis confirmed the expression of collagen type II and the cartilage-specific proteoglycan aggrecan. In summary, human adipose tissue may represent a novel plentiful source of multipotential stem cells capable of undergoing chondrogenesis in vitro.

Regenerative medicine is evolving toward a powerful new paradigm of functional restoration. With the ethical use of gene therapy or through the manipulation of autologous tissues, improved tissue replacements may soon be available. The promise of engineered whole organs, although fraught with technical hurdles, remains on the horizon. As these advances occur, physicians and surgeons of the twenty-first century will possess ever more powerful tools to restore form and function.

Surgical researchers were among the first to describe the different phases of wound healing and the events in tissue repair and regeneration that were taking place during each phase. The understanding of these events has been significantly enhanced in recent years by modern techniques in molecular and cellular biology. In this article, we discuss new findings in scarless fetal repair, angiogenesis in wound healing, and keloid pathogenesis. This serves to highlight the advances that have been made and also how much remains to be understood.

The developing fetus has the ability to heal wounds by regenerating normal epidermis and dermis with restoration of the extracellular matrix (ECM) architecture, strength, and function. In contrast, adult wounds heal with fibrosis and scar. Scar tissue remains weaker than normal skin with an altered ECM composition. Despite extensive investigation, the mechanism of fetal wound healing remains largely unknown. We do know that early in gestation, fetal skin is developing at a rapid pace and the ECM is a loose network facilitating cellular migration. Wounding in this unique environment triggers a complex cascade of tightly controlled events culminating in a scarless wound phenotype of fine reticular collagen and abundant hyaluronic acid. Comparison between postnatal and fetal wound healing has revealed differences in inflammatory response, cellular mediators, cytokines, growth factors, and ECM modulators. Investigation into cell signaling pathways and transcription factors has demonstrated differences in tyrosine phosphorylation patterns and homeobox gene expression. Further research may reveal novel genes essential to scarless repair that can be manipulated in the adult wound and thus ameliorate scar.

Craniofacial surgery is an important conduit for tissue-engineering applications. As interdisciplinary collaborations improve, we can expect to see remarkable progress in de novo tissue synthesis, replacement, and repair. Ultimately, we may one day find that gene-modified cell-based tissue-engineering strategies will succeed today's reconstructive strategies. In this review, we highlight the major gene- and cell-based preclinical tools and techniques that are currently being developed to solve common craniofacial problems.

Human processed lipoaspirate (PLA) cells are multipotent stem cells, capable of differentiating into multiple mesenchymal lineages (bone, cartilage, fat, and muscle). To date, differentiation to nonmesodermal fates has not been reported. This study demonstrates that PLA cells can be induced to differentiate into early neural progenitors, which are of an ectodermal origin. Undifferentiated cultures of human PLA cells expressed markers characteristic of neural cells such as neuron-specific enolase (NSE), vimentin, and neuron-specific nuclear protein (NeuN). After 2 weeks of treatment of PLA cells with isobutylmethylxanthine, indomethacin, and insulin, about 20 to 25 percent of the cells differentiated into cells with typical neural morphologic characteristics, accompanied by increased expression of NSE, vimentin, and the nerve-growth factor receptor trk-A. However, induced PLA cells did not express the mature neuronal marker, MAP, or the mature astrocyte marker, GFAP. It was also found that neurally induced PLA cells displayed a delayed-rectifier type K+ current (an early developmental ion channel) concomitantly with morphologic changes and increased expression of neural-specific markers. The authors concluded that human PLA cells might have the potential to differentiate in vitro into cells that represent early progenitors of neurons and/or glia.

Early in gestation, fetal wounds are capable of healing scarlessly. Scarless healing in the fetus is characterized by regeneration of an organized dermis with normal appendages and by a relative lack of inflammation. Although there is a transition period between scarless and scar-forming repair, scarless healing also depends on wound size and the organ involved. The ability to heal scarlessly, furthermore, appears to be intrinsic to fetal skin. Unique characteristics of fetal fibroblasts, inflammatory cells, extra-cellular matrix, cytokine profile, and developmental gene regulation may be responsible for the scarless phenotype of early gestation fetal wounds. With the current knowledge, only minimal success has been achieved with the topical application of neutralizing antibodies, antisense oligonucleotides, and growth factors to improve wound-healing outcomes. Thus, further investigation into the mechanisms underlying scarless repair is crucial in order to devise more effective therapies for scar reduction and the treatment of cirrhosis, scleroderma, and other diseases of excessive fibrosis.

Plastic surgery residency program directors are frequently interested in predictors of future career direction in their applicants. Many programs strive to train leaders in academic plastic surgery. To determine what factors may predict the ultimate fate of graduating plastic surgery residents, the authors reviewed the application files of 33 former residents from a single, major plastic surgery training program. The data from 29 residents were available for analysis. Nearly half of the residents graduating from the plastic surgery training program went into private practice. Two factors, the number of years taken off for research before entering the plastic surgery residency and the presence of children, were found to be indicative of a candidate's future career path. Of particular note, there was no difference between academic graduates and nonacademic graduates with regard to their intentions in their letters of recommendation and personal statements. This information is useful to both academic program directors and resident applicants.

The early-gestation fetus heals dermal wounds rapidly and scarlessly. This phenomenon appears to be intrinsic to fetal skin and independent of the intrauterine environment. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to scarless repair. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults.

We retrospectively reviewed eight patients with biopsy-proven anorectal Kaposi's sarcoma (KS) treated between 1984 and 1989 at San Francisco General Hospital. All patients were homosexual men with the acquired immunodeficiency syndrome (AIDS). The average age was 34 years. Three patients had primary rectal KS without metastases. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients with advanced AIDS received no specific treatment for anorectal KS. Follow-up ranged from 1 month to 5 years. Three of the untreated patients and the three patients treated with chemotherapy or radiotherapy were alive 1 month to 5 years after diagnosis. Aggressive surgical treatment of anorectal KS is not indicated.