ABSTRACT
Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative, soft tissue tumor. It has a propensity for deep invasion but a low risk for distant metastasis. The classic presentation is a slowly progressive, painless, and erythematous to purpuric patch on the trunk or arms. A deep, subcutaneous punch biopsy or incisional biopsy should be performed for diagnosis in all suspected cases; wide undermining of the skin is to be avoided for minimizing the risk of tumor seeding and for retaining the feasibility of histopathologic examination of re-excisions. Histopathologic distinction of DFSP from dermatofibroma requires immunohistochemical assessment for CD34, factor XIIIa, nestin, apolipoprotein D, and cathepsin K. Management of this cutaneous sarcoma involves a multidisciplinary oncologic approach. Surgical excision is usually the first step in management. DFSP has a high propensity for local recurrence, even when surgical margins are negative; therefore, radiation therapy or rarely systemic therapy is recommended, especially for locally advanced or metastatic cases. The indolent nature of DFSP requires lifelong surveillance for recurrence; however, most recurrences occur within 3 years of the primary excision. The median time for the development of a local recurrence is estimated to be 32 months. An emerging theragnostic transmembrane receptor target, folate hydrolase-1 (FOLH1; prostate-specific membrane antigen), has been expressed in benign dermatofibromas and in high-grade sarcomatous phenotypes. These findings suggest that DFSP may also express FOLH1, which could allow for surveillance with FOLH1 PET/CT and antibody-mediated brachytherapy.
Subject(s)
Dermatofibrosarcoma/therapy , Skin Neoplasms/therapy , Antigens, Surface/metabolism , Biopsy , Dermatofibrosarcoma/diagnosis , Dermatofibrosarcoma/pathology , Glutamate Carboxypeptidase II/metabolism , Humans , Margins of Excision , Neoplasm Recurrence, Local , Positron Emission Tomography Computed Tomography , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Time FactorsABSTRACT
OBJECTIVE: To delineate the role of T-helper 2 (Th2) cytokines in the induction of trauma induced myeloid suppressor cells (TIMSC) and the regulation of nitric oxide production. BACKGROUND: Trauma induces myeloid cells that express CD11b+/Gr1+ and arginase 1 and exhibit an immune suppressing activity. This article explores the mechanisms that induce TIMSC and the effects on nitric oxide production in response to endotoxin. METHODS: TIMSC were studied in response to Th2 cytokines and a subsequent challenge to endotoxin. The role of Th2 cytokines was studied in STAT6-/- mice. Accumulation of TIMSC in spleens was studied using flow cytometry and immunhistochemistry. Plasma was recovered to measure accumulation of nitric oxide metabolites. RESULTS: TIMSC accumulated in the spleen of injured mice and were particularly sensitive to IL-4 and IL-13 with large inductions of arginase activity. Significant blunting in both the accumulation of TIMSC in the spleen and induction of arginase 1 was observed in STAT6-/- mice after physical injury. Accumulation of nitric oxide metabolites to endotoxin was observed in STAT6-/- mice. CONCLUSION: This study shows that induction of CD11b+/Gr1+ cells after physical injury play an essential role in the regulation of nitric oxide production after a septic challenge. The accumulation and induction of arginase 1 in TIMSC is Th2 cytokine dependent. To our knowledge, the role of TIMSC in the regulation of nitric oxide is a novel finding. This observation adds to the possibility that TIMSC could play an important role in immunosuppression observed after physical injury.
Subject(s)
Endotoxins/pharmacology , Myeloid Cells/metabolism , Nitric Oxide/metabolism , STAT6 Transcription Factor/pharmacology , Wounds and Injuries/immunology , Animals , Arginase/metabolism , CD11b Antigen/metabolism , Cells, Cultured , Enzyme Induction , Flow Cytometry , Immune Tolerance , Immunohistochemistry , Interleukin-13/immunology , Interleukin-13/metabolism , Interleukin-4/immunology , Interleukin-4/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Myeloid Cells/immunology , Receptors, Chemokine/metabolism , Signal Transduction/drug effects , Spleen/cytology , Th2 Cells/immunology , Th2 Cells/metabolismABSTRACT
Several nutritional alternatives exist to provide critically ill patients sufficient calories to meet metabolic demands. Intuitively, investigators, nutritionists, and clinicians have pursued the goal of providing high-calorie nutrition support, believing that this would improve outcomes. There is little evidence, however, that meeting caloric goals is of significant benefit. In fact, accumulating data suggest that feeding patients below previously described caloric goals is associated with better outcomes, including decreases in hospital stay, ventilator dependence, use of antibiotics, and even mortality. This suggests that permissive underfeeding could replace the paradigm of meeting measured caloric goals. Prospective evidence to support adoption of permissive underfeeding is lacking, however. Appropriate clinical studies are necessary to prove its safety and efficacy.
Subject(s)
Critical Illness , Energy Intake , Nutritional Support , Humans , Nutritional Status , Parenteral Nutrition , StarvationABSTRACT
Dr. Stanley Dudrick invented total parenteral nutrition in 1968, providing a desperately needed therapy to those patients who could not eat. It has since saved thousands of patients worldwide. Nutrition interventions (NI) in surgical/trauma and critically ill patients have evolved dramatically during the last 20 years from a supportive therapy to a clear therapeutic role. Like any other form of therapy, NI will benefit patients when adequately indicated and prescribed. NI, however, may cause significant side effects and harm when poorly ordered. This article reviews the indications for the prescription of the different forms of NI available to the clinician caring for the surgical patient.