Brian Gastman

Indocyanine green SPY elite-assisted sentinel lymph node biopsy in cutaneous melanoma.

Background: Sentinel lymph node biopsy is the standard of care for intermediate-depth and high-risk thin melanomas. Recently, indocyanine green and near-infrared imaging have been used to aid in sentinel node biopsy. The present study aimed to determine the feasibility of sentinel lymph node biopsy with indocyanine green SPY Elite navigation and to critically evaluate the technique compared with the standard modalities. Methods: A retrospective review of 90 consecutive cutaneous melanoma patients who underwent sentinel lymph node biopsy was performed. Two cohorts were formed: group A, which had sentinel lymph node biopsy performed with blue dye and radioisotope; and group B, which had sentinel lymph node biopsy performed with radioisotope and indocyanine green SPY Elite navigation. The cohorts were compared to assess for differences in localization rates, sensitivity and specificity of sentinel node identification, and length of surgery. Results: The sentinel lymph node localization rate was 79.4 percent using the blue dye method, 98.0 percent using the indocyanine green fluorescence method, and 97.8 percent using the radioisotope/handheld gamma probe method. Indocyanine green fluorescence detected more sentinel lymph nodes than the vital dye method alone (p = 0.020). A trend toward a reduction in length of surgery was noted in the SPY Elite cohort. Conclusions: Sentinel lymph node mapping and localization in cutaneous melanoma with the indocyanine green SPY Elite navigation system is technically feasible and may offer several advantages over current modalities, including higher sensitivity and specificity, decreased number of lymph nodes sampled, decreased operative time, and potentially lower false-negative rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, II.

Sources of federal funding in plastic and reconstructive surgery research.

Background: In the last several years, federal funding has become increasingly difficult to obtain. The purpose of this project was to define the level of federal funding among plastic surgeons in the modern era. Methods: The authors evaluated members of the Plastic Surgery Research Council because of their expected invested interested in research. The authors collected information from 1998 to 2012 on funding using curricula vitae and publically available online tools. Data on Plastic Surgery Foundation funding was also collected to determine its role in supporting federally funded investigators. Results: Of 256 individuals, the authors found 41 to be primary investigators on federally funded grants, with the majority receiving one to two awards. Common subtypes of awards included National Institutes of Health R01 (n = 15), K08 (n = 9), and R21 (n = 6). Limited funding from the National Science Foundation and the Department of Defense was identified. Despite a steady number of available National Institutes of Health awards, plastic surgery recipients have grown in number over the past 15 years. In a review of 20 years of Plastic Surgery Foundation awards, 113 Plastic Surgery Research Council members (44.1 percent) were awardees, averaging 1.8 awards per person. Twenty-nine Plastic Surgery Foundation awardees were also recipients of federal funding; 12 individuals received federal funding without prior Plastic Surgery Foundation funding. Conclusions: A search of plastic surgeons indicates a limited but increasing number of individuals receive federal funding. Plastic Surgery Foundation awards appear to be helpful in supporting investigators as they move to larger federal awards.

Interleukin-7 inhibits tumor-induced CD27-CD28- suppressor T cells: implications for cancer immunotherapy.

Purpose: We have previously reported that many types of tumors can induce changes in human T cells that lead to the acquisition of suppressive function and phenotypic alterations resembling those found in senescent T cells. In the present study, we find a role for interleukin 7 (IL-7) in protecting T cells from these changes and further define involved signaling pathways. Experimental Design: We evaluated the ability of IL-7 treatment to prevent the gain of suppressive function and phenotypic alterations in human T cells after a short coculture with tumor cells in vitro. We then used inhibitors of components of the phosphoinositide 3-kinase (PI3K)/AKT pathway and short interfering RNA knockdown of Mcl-1 and Bim to evaluate the role of these signaling pathways in IL-7 protection. Results: We found that IL-7 inhibits CD27/CD28 loss and maintains proliferative capacity, IL-2 production, and reduced suppressive function. The protective ability of IL-7 depended on activation of the PI3K/AKT pathway, which inhibited activation of glycogen synthase kinase 3β, which, in turn, prevented the phosphorylation and loss of Mcl-1. We further showed a key role for Mcl-1 in that its knockdown or inhibition abrogated the effects of IL-7. In addition, knockdown of the Mcl-1 binding partner and proapoptotic protein Bim protected T cells from these dysfunctional alterations. Conclusion: These observations confirm the role for Bcl-2 family members in cytokine signaling and suggest that IL-7 treatment in combination with other immunotherapies could lead to new clinical strategies to maintain normal T-cell function and reduce tumor-induced generation of dysfunctional and suppressor T cells. Clin Cancer Res; 17(15); 4975–86. ©2011 AACR.

Mcl-1 regulates reactive oxygen species via NOX4 during chemotherapy-induced senescence

Mcl-1, a Bcl-2 family member, is highly expressed in a variety of human cancers and is believed to enhance tumorigenic potential and chemotherapy resistance through the inhibition of apoptosis and senescence. We previously reported that Mcl-1′s regulation of chemotherapy-induced senescence (CIS) is dependent on its ability to prevent reactive oxygen species (ROS) generation. In this report, we demonstrate that Mcl-1-regulated CIS requires not only ROS, but specifically mitochondrial ROS, and that these events are upstream of activation of the DNA damage response, another necessary step toward senescence. Mcl-1′s anti-senescence activity also involves the unique ability to inhibit ROS formation by preventing the upregulation of pro-oxidants. Specifically, we found that NADPH oxidases (NOXs) are regulated by Mcl-1 and that NOX4 expression in particular is a required step for CIS induction that is blocked by Mcl-1. Lastly, we illustrate that by preventing expression of NOX4, Mcl-1 limits its availability in the mitochondria, thereby lowering the production of mitochondrial ROS during CIS. Our studies not only define the essential role of Mcl-1 in chemoresistance, but also for the first time link a key pro-survival Bcl-2 family member with the NOX protein family, both of which have significant ramifications in cancer progression.

Advances in diagnosis and treatment of nonmelanoma skin cancer.

AbstractThe incidence of nonmelanoma skin cancer (NMSC) is rising. Research in the field of these tumors is aimed toward developing earlier and less invasive diagnostic methods and more effective, more accessible therapeutic options. Although there is much advancement in the diagnosis and treatment of NMSC, there are few literatures cataloging these developments. The aim of this review was to present the sensitivity and specificity of new imaging modalities, the dosing regimen and clearance rates of topical treatments, newer systemic treatment modalities, and discuss developments in the use of radiation as a mode of therapy. Recent developments in the diagnosis of NMSC include imaging modalities such as reflectance confocal microscopy, elastic scattering spectroscopy, and spectrophotometric intracutaneous analysis. Recent advances in the treatment of these tumors include systemic therapies such as epidermal growth factor receptor inhibitors, and topical immunomodulating drugs such as imiquimod. The progress in the diagnosis and treatment of these tumors is a gradual but fruitful growth. Scientists and clinicians alike must continue their exploration and study to address these tumors and, hopefully in the future, prevent their occurrence.

Indocyanine green-guided sentinel lymph node biopsy for periocular tumors.

Purpose: To compare the accuracy of indocyanine green (ICG)–guided sentinel lymph node biopsy to sentinel lymph node biopsy performed with technetium-99m in eyelid and in conjunctival malignancies. Methods: Review of a consecutive series of adult patients undergoing sentinel lymph node biopsy for eyelid and conjunctival malignancies between 2009 and 2013. Only patients undergoing both ICG-guided and technetium-99m–guided sentinel lymph node biopsies were included. Results: Five patients were identified: 3 women and 2 men. Four had conjunctival melanoma and 1 had eyelid melanoma. ICG aided in localization and confirmation of the sentinel nodes identified by technetium-99m, and all sentinel lymph nodes identified by technetium-99m were identified by ICG. All patients who underwent both sentinel lymph node modalities had negative lymph node biopsies for micrometastasis, but metastatic disease eventually developed in 1 patient. No safety concerns were identified with the use of ICG in the ocular adnexal region. Conclusions: For certain periocular malignancies, ICG-guided sentinel lymph node biopsy safely identifies sentinel lymph nodes intraoperatively possibly to a similar extent compared with technetium-99m–guided methods.

The Anterolateral Thigh Flap as the Flap of Choice for Scalp Reconstruction

Introduction: Large scalp soft tissue defects can present difficulties with reconstruction. The ideal flap for scalp reconstruction has yet to be described although the latissimus dorsi flap is frequently referred to as the first choice in this setting. Patients and Methods: Following institutional review board approval, the authors reviewed their experience in scalp reconstruction for the past 4 years. Patient demographics, reconstruction indication, flap choice, complications, and outcomes were recorded. Results: Thirteen patients underwent scalp reconstruction with an anterolateral thigh (ALT) free flap. In most patients, the indication was resection of a cutaneous malignancy. In all but 1 patient the facial or more proximal vessels were used for anastomosis. None of the patients required vein grafts to increase pedicle length. The median flap surface area was 156u200acm2. One flap had vascular compromise. All donor sites healed without complications. Discussion: The ALT flap can emerge as the flap of choice for scalp reconstruction, even when proximal neck vessels are used as the recipient targets. Using a suprafascial dissection and extending the vascular pedicle to the profunda femoris artery can optimize its role in this setting. The ALT flap provides excellent cosmesis and durable scalp coverage with minimal donor site morbidity.

Malignant Pyoderma Associated with Granulomatosis with Polyangiitis (Wegener Granulomatosis) as a Unique Indication for Facial Vascularized Composite Allotransplantation: Part i

Background: Granulomatosis with polyangiitis (Wegener granulomatosis) is a rare disease that commonly starts in the craniofacial region and can lead to considerable facial disfigurement. Granulomas and vasculitis, however, can involve many other tissues (especially pulmonary and renal). Dermatologic and subcutaneous components can lead to malignant pyoderma. Methods: The authors describe a unique pathologic condition, where significant Le Fort type trauma was associated with subsequent development of granulomatosis with polyangiitis and malignant pyoderma. Successive operations to excise necrotic tissue and reconstruct the defects were followed by worsening inflammation and tissue erosions. Trauma and surgery in proximity to the eye and sinuses masked the initial clinical presentation and led to delay in diagnosis and disease progression. The resultant facial disfigurement and tissue loss were substantial. Results: Despite multiple confounding factors, accurate diagnosis was eventually established. This was based on persistence of sinus inflammations in the absence of infective agents, proven sterility of lung lesions, and antineutrophil cytoplasmic antibody positivity with proteinase 3 specificity. Skin lesion biopsy specimens were identified as pyoderma gangrenosum and later as malignant pyoderma. Institution of immunosuppressive therapy allowed successful control of the disease and wound healing. The resulting craniofacial destruction, however, necessitated facial vascularized composite allotransplantation. Conclusion: Recognition of this rare pathologic association is essential, to prevent delays in diagnosis and treatment that can lead to major craniofacial tissue loss. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Extending the Cordeiro maxillofacial defect classification system for use in the era of vascularized composite transplantation.

Summary: There is a growing interest in the use of vascularized composite transplantation to reconstruct major facial and craniofacial deformities. This phenomenon is driven both by the success of recent transplantations to functionally and aesthetically restore patients and by an increase in the number of centers entering this challenging field. The authors new classification system, based on a well-established schema, allows proper documentation of the needs of these patients and enhancement of interinstitutional communication for outcomes reporting.

Watershed Areas in Face Transplantation

BACKGROUNDnThe maxillary artery has traditionally been considered the main blood supply of the facial skeleton. However, the deep and concealed location makes the harvest of facial allografts based on this artery challenging, giving preference to the facial artery. There is growing evidence that the junction between the hard and soft palate may represent a watershed area in facial artery-based allografts. The aim of this study was to review the occurrence of partial allograft necrosis and modify the available craniofacial techniques, allowing for a reliable harvest of maxillary artery-based facial allografts.nnnMETHODSnPubMed/MEDLINE databases were searched for articles presenting allograft perfusion details and the occurrence of partial flap necrosis. Next, 25 fresh cadaver heads were used: eight allografts were harvested by means of a traditional Le Fort III approach, in six the maxillary artery was injected with latex, in three cadaver heads lead oxide gel was injected in the maxillary artery, and eight full facial allografts were harvested through a modified approach.nnnRESULTSnSeven patients developed palatal fistulas or palatal necrosis (41 percent) when allograft was perfused through the facial artery. The traditional Le Fort III approach demonstrated consistent injury to maxillary artery/branches. The modified approach allowed for preservation of the maxillary artery under direct vision.nnnCONCLUSIONSnCurrent facial transplantation outcomes indicate that facial artery-based allografts containing Le Fort III bony components can experience compromised palate perfusion. The described modified Le Fort III approach allowed safe dissection of the maxillary artery, preserving the arterial blood supply to the facial skeleton.nnnCLINICAL QUESTION/LEVEL OF EVIDENCEnTherapeutic, V.Background: The maxillary artery has traditionally been considered the main blood supply of the facial skeleton. However, the deep and concealed location makes the harvest of facial allografts based on this artery challenging, giving preference to the facial artery. There is growing evidence that the junction between the hard and soft palate may represent a watershed area in facial artery–based allografts. The aim of this study was to review the occurrence of partial allograft necrosis and modify the available craniofacial techniques, allowing for a reliable harvest of maxillary artery–based facial allografts. Methods: PubMed/MEDLINE databases were searched for articles presenting allograft perfusion details and the occurrence of partial flap necrosis. Next, 25 fresh cadaver heads were used: eight allografts were harvested by means of a traditional Le Fort III approach, in six the maxillary artery was injected with latex, in three cadaver heads lead oxide gel was injected in the maxillary artery, and eight full facial allografts were harvested through a modified approach. Results: Seven patients developed palatal fistulas or palatal necrosis (41 percent) when allograft was perfused through the facial artery. The traditional Le Fort III approach demonstrated consistent injury to maxillary artery/branches. The modified approach allowed for preservation of the maxillary artery under direct vision. Conclusions: Current facial transplantation outcomes indicate that facial artery–based allografts containing Le Fort III bony components can experience compromised palate perfusion. The described modified Le Fort III approach allowed safe dissection of the maxillary artery, preserving the arterial blood supply to the facial skeleton. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.