Gerhard S. Mundinger

Characteristic indocyanine green lymphography findings in lower extremity lymphedema: the generation of a novel lymphedema severity staging system using dermal backflow patterns.

Background: Indocyanine green lymphography has been a highly useful modality in the clinical examination and surgical management of patients with lymphedema. No formal classification system of indocyanine green imaging findings according to the severity of lymphedema exists, however. The purpose of this study was to describe, analyze, and classify characteristic indocyanine green lymphography findings to uniformly guide surgical management of lymphedema using this modality. Methods: Forty-five patients (78 limbs) with lower extremity lymphedema underwent indocyanine green lymphography. All lymphography images were recorded in photographs and videos. Images were reviewed and analyzed to classify characteristic findings according to clinical severity as determined by Campisi clinical lymphedema staging. Results: Lymphography findings were classifiable into two patterns. Mild cases of lymphedema were characterized by a linear lymphatic channel pattern (linear pattern). In more severe cases, lymphatic channels demonstrated retrograde lymphatic flow (dermal backflow pattern) and diminution or absence of linear channel patterning. Three dermal backflow patterns, splash, stardust, and diffuse, were identified and correlated with the progression of lymphedema severity. These findings supported the generation of a novel anatomical lymphedema severity staging system, the dermal backflow staging system. Conclusions: Indocyanine green lymphography is a safe, minimally invasive, and useful tool for the surgical evaluation of extremity lymphedema. Characteristic indocyanine green lymphography patterns are consistent and correlate with clinical severity. The dermal backflow staging system can facilitate patient stratification, discussion between referring parties, and surgical planning.

The Intravascular Stenting Method for Treatment of Extremity Lymphedema with Multiconfiguration Lymphaticovenous Anastomoses

Background: In secondary extremity lymphedema, normal antegrade lymphatic flow is disrupted by the disease state. Attempts to capture aberrant retrograde lymphatic flow by means of microsurgical lymphaticovenous anastomoses have been hindered because of technical limitations. The authors applied the intravascular stenting method to the surgical correction of extremity lymphedema to generate multiconfiguration lymphaticovenous anastomoses capable of decompressing both proximal and distal lymphatic flow. Methods: Lymphatic channels were detected using indocyanine green injection and infrared scope imaging. Sites felt to be adequate for lymphaticovenous anastomosis were accessed through 2-cm skin incisions under local anesthesia. Using the intravascular stenting method, the authors performed a total of 39 lymphaticovenous anastomoses (15 flow-through, 11 end-to-end, eight end-to-side, two double end-to-end, two end-to-end/end-to-side, and one &pgr;-type) on both the proximal and distal ends of lymphatic channels in 14 female patients with upper (n = 2) and lower (n = 12) extremity lymphedema. Results: At an average follow-up of 8.9 months, average limb girth decreased 3.6 cm (range, 1.5 to 7 cm) or 11.3 percent (range, 4 to 33 percent). There was a greater reduction in cross-sectional area with increasing number of lymphaticovenous anastomoses per limb. Conclusions: The intravascular stenting method facilitated multiconfiguration lymphaticovenous anastomoses capable of decompressing both antegrade and retrograde lymphatic flow. This approach resulted in durable reduction of both upper and lower extremity lymphedema. As multiconfiguration lymphaticovenous anastomoses are now technically feasible, the influence of the number of lymphaticovenous anastomoses and the effectiveness of specific lymphaticovenous anastomosis configurations for the treatment of lymphedema deserves further study.

Proteomic Signatures of Epidermal Growth Factor Receptor and Survival Signal Pathways Correspond to Gefitinib Sensitivity in Head and Neck Cancer

Purpose: Gefitinib targeting of the epidermal growth factor receptor (EGFR) has shown limited activity in clinical trials of head and neck squamous cell carcinoma (HNSCC). To investigate the underlying molecular mechanism, the proteomic signatures and responses of EGFR and downstream signals have been studied in a panel of HNSCC cell lines and tumor specimens pre- and post-gefitinib treatment. Experimental Design: The IC50 of gefitinib for HNSCC cell lines were determined using 3-(4,5-dmethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay. The effects of gefitinib on activation of EGFR and downstream signaling molecules were determined by Western blot, ELISA, and reverse-phase protein microarray (RPMA). The biomarkers involved in the signaling pathways were examined in HNSCC tumor specimens from patients in a phase I gefitinib trial. Results:In vitro, gefitinib inhibited cell proliferation with differing IC50, and suppressed activation of EGFR and downstream signaling molecules protein kinase B (AKT), extracellular signal-regulated kinase 1/2, signal transducer and activator of transcription 3 (STAT3), and nuclear factor κB. The drug sensitivity was statistically correlated with activation of phosphorylated AKT (p-AKT) and phosphorylated STAT3 (p-STAT3) detected by ELISA, and consistent with results measured by RPMA. In patient samples, a broad suppression of activation of EGFR and downstream signaling molecules was observed in a molecular responder patient, in contrast to a lack of inhibition or increased activation of biomarkers in different pathways in nonresponder patients. Conclusions: Gefitinib sensitivity is correlated with p-AKT and p-STAT3 activation in HNSCC cell lines and tumor specimens. p-AKT and p-STAT3 could serve as potentially useful biomarkers and drug targets for further development of novel therapeutic agents for HNSCC.

Histopathology of chronic rejection in a nonhuman primate model of vascularized composite allotransplantation.

Background Chronic rejection of vascularized composite allografts (VCA) is an emerging phenomenon that may decrease long-term allograft survival and impair allograft function. Although intimal hyperplasia has been reported in human hand transplants, chronic changes in VCAs remain poorly described. Methods We developed a nonhuman primate model of face transplantation to evaluate the effect of various immunosuppressive regimens on allograft survival that we have previously reported. Nineteen grafts were successfully transplanted and serially biopsied to assess for rejection. Five VCA grafts with long-term survival (>200 days) were weaned off immunosuppression. We performed additional histologic and immunohistochemical studies on previously collected samples. Results All five grafts developed features consistent with chronic rejection, including neointimal proliferation, transplant vasculopathy, vessel wall fibrosis, progressive luminal occlusion, and tertiary lymphoid follicles. Review of 186 serial allograft skin and subcutaneous tissue biopsies revealed that tertiary follicles and vascular changes developed in the absence of acute skin rejection. No relationship was found between alloantibody production and these changes. Conclusions Recognition of these characteristics of VCA chronic rejection is important for diagnosis in clinical hand and face transplantation. Studies directed towards minimizing VCA chronic rejection responses may be required to improve long-term outcomes.

Digital artery perforator (DAP) flaps: Modifications for fingertip and finger stump reconstruction

UNLABELLED Various fingertip reconstructions have been reported for situations where microsurgical finger replantation is impossible. One method is the digital artery perforator (DAP) flap. Herein we report 13 DAP flaps for fingertip and finger stump reconstruction following traumatic finger amputations, highlighting modifications to the originally described DAP flap. METHODS From October 1998 to December 2007, a total of 13 fingers (11 patients) underwent fingertip and finger stump reconstruction with modified DAP flaps following traumatic finger amputations. We performed six adipocutaneous flaps, three adipose-only flaps, two supercharged flaps and two extended flaps. Flap size ranged from 1.44 to 8 cm(2) (average 3.25 cm(2)). RESULTS All flaps survived completely with the exception of partial skin necrosis in two cases. One of these cases required debridement and skin grafting. Our initial three cases used donor-site skin grafting. The donor site was closed primarily in the 10 subsequent cases. No patients showed postoperative hypersensitivity of repaired fingertips. Semmes-Weinstein (SW) test result for flaps including a digital nerve branch did not differ from those without (average 4.07 vs. 3.92). CONCLUSIONS Modified DAP flaps allow for preservation of digital length, volume and finger function. They can be raised as adiposal-only flaps or extended flaps and supercharged through perforator-to-perforator anastomoses. The donor defect on the lateral pulp can be closed primarily or by skin grafting. For traumatic fingertip and finger stump reconstructions, DAP flaps deliver consistent aesthetic and functional results.

Ocular injury, visual impairment, and blindness associated with facial fractures: a systematic literature review.

Background: Injuries to the face can potentially lead to destruction of vital structures, with devastating sequelae to the patient. Facial fractures, especially of the midface, are often complicated by ocular injuries. The purpose of this study was to systematically review the literature to better understand specific fracture patterns associated with ocular injuries, including visual impairment and blindness. Methods: The PubMed, EMBASE, and Cochrane databases from January of 2004 to April of 2010 were systematically reviewed to identify relevant studies. Only those that investigated facial fractures with concomitant ocular injuries, visual impairment, and/or blindness were included. Studies that described nonfacial fractures or those that only focused on the function of extraocular muscles were excluded. Case reports, nonsystematic reviews, and studies with fewer than 10 patients were also excluded. Results: Eleven articles met study criteria and were included for analysis. There were a total of 14,535 patients, with an average of 1211 patients (range, 39 to 4426) per study. Level of evidence included levels II (n = 1 study), III (n = 1), and IV (n = 9). The mean reported rate of acute visual loss was 1.7 percent. Periorbital and orbital blowout fractures were more often complicated by ocular injuries compared with other facial fracture patterns. High-impact zygomatic fractures were most commonly associated with blindness. Conclusions: Existing studies exploring ocular injuries, visual impairment, and blindness associated with facial fractures offer conflicting data. Specifically directed studies are required so that significant correlations between specific fracture patterns and specific ocular injuries can be drawn. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

Chronic rejection in vascularized composite allografts.

Purpose of reviewTo convey key issues surrounding chronic rejection in vascularized composite tissue allotransplantation (VCA), and to highlight pathologic features consistent with VCA chronic rejection. Recent findingsFeatures consistent with chronic rejection have been reported in three VCA animal models, and have been observed in a paucity of human knee and hand transplants. These features include transplant vasculopathy with intimal hyperplasia, tertiary lymphoid follicles, graft fibrosis, and graft edema. Transplant vasculopathy has been the most consistent finding across cases, and has resulted in graft dysfunction and loss. Antibody-mediated rejection has not been conclusively reported in animal models or human subjects, although some cases have demonstrated donor-specific antibody in conjunction with C4d deposition. Multiple immunologic and non-immunologic mechanisms of VCA chronic rejection have been proposed. SummaryAs in solid organ transplantation, chronic rejection in VCA remains ill-defined. Transplant vasculopathy appears to be a key feature of chronic VCA rejection, whereas tertiary lymphoid follicles, graft fibrosis, and graft edema appear to be less-specific findings. Intimal hyperplasia can be detected with advanced imaging modalities.

Adult Pancreatic Hemangioma: Case Report and Literature Review

We report an adult pancreatic hemangioma diagnosed on pathological specimen review following pylorus preserving pancreaticoduodenectomy for a symptomatic cystic mass in the head of the pancreas. Eight cases of adult pancreatic hemangioma have been reported in literature since 1939. Presenting symptoms, radiographic diagnosis, pathologic characteristics, and treatment of adult pancreatic hemagiomas are discussed following review of all published cases.

Antibiotics and Facial Fractures: Evidence-Based Recommendations Compared with Experience-Based Practice

Efficacy of prophylactic antibiotics in craniofacial fracture management is controversial. The purpose of this study was to compare evidence-based literature recommendations regarding antibiotic prophylaxis in facial fracture management with expert-based practice. A systematic review of the literature was performed to identify published studies evaluating pre-, peri-, and postoperative efficacy of antibiotics in facial fracture management by facial third. Study level of evidence was assessed according to the American Society of Plastic Surgery criteria, and graded practice recommendations were made based on these assessments. Expert opinions were garnered during the Advanced Orbital Surgery Symposium in the form of surveys evaluating senior surgeon clinical antibiotic prescribing practices by time point and facial third. A total of 44 studies addressing antibiotic prophylaxis and facial fracture management were identified. Overall, studies were of poor quality, precluding formal quantitative analysis. Studies supported the use of perioperative antibiotics in all facial thirds, and preoperative antibiotics in comminuted mandible fractures. Postoperative antibiotics were not supported in any facial third. Survey respondents (n = 17) cumulatively reported their antibiotic prescribing practices over 286 practice years and 24,012 facial fracture cases. Percentages of prescribers administering pre-, intra-, and postoperative antibiotics, respectively, by facial third were as follows: upper face 47.1, 94.1, 70.6; midface 47.1, 100, 70.6%; and mandible 68.8, 94.1, 64.7%. Preoperative but not postoperative antibiotic use is recommended for comminuted mandible fractures. Frequent use of pre- and postoperative antibiotics in upper and midface fractures is not supported by literature recommendations, but with low-level evidence. Higher level studies may better guide clinical antibiotic prescribing practices.

Severe infectious complications following frontal sinus fracture: the impact of operative delay and perioperative antibiotic use.

Background: The purpose of this study was to investigate whether a delay in operative management of frontal sinus fractures is associated with increased risk of serious infections. Methods: Retrospective chart review was performed of 242 consecutive patients with surgically managed frontal sinus fractures who presented to the R Adams Cowley Shock Trauma Center between 1996 and 2011. Collected patient characteristics included demographics, surgical management, hospital course, and complications. All computed tomographic imaging was reviewed to evaluate involvement of the posterior table and nasofrontal outflow tract. Serious infections included meningitis, encephalitis, brain abscess, frontal sinus abscess, and osteomyelitis. Delayed operative interventions were defined as procedures performed more than 48 hours after admission. Adjusted relative risk estimates were obtained using multivariable regression. Results: There were 14 serious infections (5.8 percent). All patients with serious infections had both involvement of the posterior table and nasofrontal outflow tract injury. The cumulative incidence of serious infection in these patients was 10.8 percent. After adjustments for confounding, multivariable regression showed that operative delay beyond 48 hours was independently associated with a 4.03-fold (p < 0.05) increased risk for serious infection; external cerebrospinal fluid drainage catheter use and local soft-tissue infection conferred a 4.09-fold (p < 0.05) and 5.10-fold (p < 0.001) increased risk, respectively. Antibiotic use beyond 48 hours postoperatively was not associated with fewer infections. Conclusions: Delay in operative management of frontal sinus fractures in patients requiring operative intervention is associated with an increased risk for serious infections. Continued antibiotic prophylaxis beyond the perioperative period provides little benefit in preventing serious infections. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.