Faculty Bibliography

PURPOSE: Resecting oral squamous cell carcinoma (SCC) with an appropriate margin of uninvolved tissue is critical in preventing local recurrence and making the decision regarding postoperative radiation therapy. This task can be difficult due to the discrepancy between margins measured intraoperatively and those measured microscopically by the pathologist after specimen processing. The goal of this study is to quantify and compare the amount of margin discrepancy observed based on tumor location and staging. MATERIALS AND METHODS: Forty-one patients who underwent resective surgery with curative intent for primary oral SCC were included in this study. All patients underwent resection of the tumor with a measured 1 cm margin by one attending surgeon. Specimens were then submitted for processing and reviewing and histopathologic margins were measured. The closest histopathologic margin was compared with the in situ margin (1 cm) to determine percentage discrepancy. Percent discrepancies were grouped by locations (buccal mucosa, mandibular alveolar ridge, and retromolar trigone in group 1; maxillary alveolar ridge and palate in group 2; and oral tongue in group 3) and analyzed. Percent discrepancies grouped by stages T1/T2 or T3/T4 were compared. RESULTS: The mean discrepancy for all patients was a statistically significant 59.02% (P < .0001). The mean discrepancy was 71.90% for group 1, 53.33% for group 2, and 42.14% for group 3 (P = .0133). The mean discrepancy in T1/T2 tumors was 51.48% and in T3/T4 tumors was 75.00% (P = .0264). CONCLUSIONS: Oral SCC margin discrepancies after resection and specimen processing are highly significant. Tumors located in the buccal mucosa, retromolar trigone, and mandibular alveolar ridge show significantly greater discrepancies than tumors of the maxilla or oral tongue. Late stage tumors also show significantly greater margin discrepancies. These findings suggest that it might be prudent to consider oral site and staging when outlining margins to ensure adequacy of resection

OBJECTIVE: To determine the rate of hematoma formation in drainless deep-plane rhytidectomy and compare it with the rate using the same technique with the use of fibrin glue. METHODS: This is a retrospective review of 605 patients (78 male and 527 female) who, over a 6-year period, underwent deep-plane face-lift surgery (n = 544) or lateral superficial musculoaponeurotic system (SMAS)ectomy (n = 61) by the senior author (S.S.R.) without the use of surgical drains. One hundred forty-six consecutive patients underwent rhytidectomy without fibrin tissue glue, and the following 459 consecutive patients were sprayed with fibrin glue under the flap prior to flap closure. Pressure dressings were used on all patients for 24 hours. RESULTS: None of the patients in either group had major or expanding hematomas requiring operative intervention. In the group of patients treated without fibrin glue (n = 146), there were 5 minor, nonexpanding hematomas, all managed by needle aspiration. This is a minor hematoma rate of 3.4%. In the fibrin glue group (n = 459), there were 2 hematomas, for a rate of 0.4%. Using a Fisher exact test, we found a statistically significant decrease in the hematoma rate from 3.4% to 0.4% (P = .01). Male patients had a higher hematoma rate than female patients, and only men had significantly fewer hematomas when fibrin glue was applied (P = .01). All 7 hematomas were recognized in the first 24 hours after surgery. Of the 7 patients with hematomas, 2 (29%) had emesis in the recovery room despite medication. CONCLUSIONS: The use of fibrin glue demonstrates a significant decrease in the rate of hematoma formation. Fibrin glue may benefit male more than female patients. If meticulous hemostasis and pressure dressings are used, drains are not necessary. The prevention and prompt treatment of postoperative nausea may also help prevent hematoma formation

OBJECTIVES: Kaposi sarcoma (KS) is a vascular tumor that can affect the mucosa of the upper aerodigestive tract. Although KS is the most common malignancy in patients with acquired immunodeficiency syndrome, it is rare in immunocompetent persons. We describe an unusual presentation of KS in 2 related individuals and describe our attempts to determine whether oropharyngeal KS is associated with human herpesvirus 8 (HHV-8). METHODS: All relevant clinical and surgical information, including information on tumor histopathologic and human immunodeficiency virus (HIV) serologic tests, was abstracted from the patient charts and electronic databases. HHV-8 immunohistochemistry was performed on paraffin-fixed specimens. RESULTS: Both patient 1 and patient 2 (the nephew of patient 1) were referred for workup of a tonsillar mass that was pathologically confirmed to be KS. In each case, HIV serologic testing was negative, and a screening immunologic workup, including a quantitative natural killer cell count, a B- and T-lymphocyte count, and immunoglobulin analysis, also yielded findings that were within normal limits. Immunohistochemistry performed on 1 pathological specimen showed positive staining for the presence of HHV-8, the etiologic agent of KS. CONCLUSIONS: The presence of oropharyngeal KS in 2 related HIV-negative individuals supports a role for genetic factors in susceptibility to KS, a common exposure to an infectious agent such as HHV-8, or both. Whereas most KS cases in industrialized countries are associated with immunodeficiency, clinical and laboratory data do not suggest that either of the patients described in this report are immunodeficient. Their susceptibility to KS may be secondary to a subtle inherited defect in host resistance to HHV-8, or another unknown factor

Adhesion of leukemic cells to vascular cells may confer resistance to chemotherapeutic agents. We hypothesized that disruption of leukemic cell cytoskeletal stability and interference with vascular cell interactions would promote leukemic cell death. We demonstrate that low and nontoxic doses of microtubule-destabilizing agent combretastatin-A4-phosphate (CA4P) inhibit leukemic cell proliferation in vitro and induce mitotic arrest and cell death. Treatment of acute myeloid leukemias (AMLs) with CA4P leads to disruption of mitochondrial membrane potential, release of proapoptotic mitochondrial membrane proteins, and DNA fragmentation, resulting in cell death in part through a caspase-dependent manner. Furthermore, CA4P increases intracellular reactive oxygen species (ROS), and antioxidant treatment imparts partial protection from cell death, suggesting that ROS accumulation contributes to CA4P-induced cytotoxicity in AML. In vivo, CA4P inhibited proliferation and circulation of leukemic cells and diminished the extent of perivascular leukemic infiltrates, prolonging survival of mice that underwent xenotransplantation without inducing hematologic toxicity. CA4P decreases the interaction of leukemic cells with neovessels by down-regulating the expression of the adhesion molecule VCAM-1 thereby augmenting leukemic cell death. These data suggest that CA4P targets both circulating and vascular-adherent leukemic cells through mitochondrial damage and down-regulation of VCAM-1 without incurring hematologic toxicities. As such, CA4P provides for an effective means to treat refractory organ-infiltrating leukemias

The MHC-encoded cofactor DM catalyzes endosomal loading of peptides onto MHC class II molecules. Despite evidence from in vitro experiments that DM acts to selectively edit the repertoire of class II:peptide complexes, the consequence of DM expression in vivo, or a predictive pattern of DM activity in the specificity of CD4 T cell responses has remained unresolved. Therefore, to characterize DM function in vivo we used wild-type (WT) or DM-deficient (DM(-/-)) mice of the H-2(d) MHC haplotype and tested the hypothesis that DM promotes narrowing of the repertoire of class II:peptide complexes displayed by APC, leading to a correspondingly selective CD4 T cell response. Surprisingly, our results indicated that DM(-/-) mice do not exhibit a broadened CD4 T cell response relative to WT mice, but rather shift their immunodominance pattern to new peptides, a pattern associated with a change in class II isotype-restriction. Specifically, we found that CD4 T cell responses in WT mice were primarily restricted to the I-A class II molecule, whereas DM(-/-) mice recognize peptides in the context of I-E. The observed shift in isotype-restriction appeared to be due in part to a modification in the peripheral CD4 T cell repertoire available for peptide recognition.

BACKGROUND: Radiation alone or concurrent chemoradiation can result in severe swallowing disorders. This manuscript defines the swallowing disorders occurring at pretreatment and 3 and 12 months after completion of radiation or chemoradiation. METHODS: Forty-eight patients (10 women and 38 men) participated in this study involving videofluorographic evaluation of oropharyngeal swallow at the 3 time points. RESULTS: At baseline, patients had some swallow disorders, probably related to presence of their tumor. At 3 months posttreatment, frequency of reduced tongue base retraction, slow or delayed laryngeal vestibule closure, and reduced laryngeal elevation increased from baseline. Some disorders continued at 12 months posttreatment. Functional swallow decreased over time in patients treated with chemoradiation, but not those treated with radiation alone. DISCUSSION: Chemoradiation results in fewer functional swallowers than radiation alone at 12 months posttreatment completion

BACKGROUND: In the neck, the recipient vessels most frequently used for microsurgical reconstruction are compromised by prior surgery and radiation. METHODS: We conducted a retrospective chart review of all patients who underwent microvascular reconstruction between July 2001 and June 2005. Donor vessels, vein grafts, and flap survival were examined. RESULTS: Fourteen of 197 patients (7%) were identified with a vessel-depleted neck. All patients had undergone a prior neck dissection and radiation (100%) or chemoradiation (42%). Free flap revascularization was achieved using the transverse cervical artery with a vein graft and a cephalic vein (4 patients), thoracoacromial artery and cephalic vein (3 patients), internal mammary artery and vein (3 patients), and inferior thyroid artery and cephalic vein (1 case). In 3 patients, the reverse flow thoracodorsal artery and cephalic vein were used to vascularize the scapular flap. CONCLUSION: The cephalic vein, transverse cervical, internal mammary, and thoracoacromial vessels represent reliable alternatives in the vessel-depleted neck.

PURPOSE: This review presents the state of swallowing rehabilitation science as it relates to evidence for neural plastic changes in the brain. The case is made for essential collaboration between clinical and basic scientists to expand the positive influences of dysphagia rehabilitation in synergy with growth in technology and knowledge. The intent is to stimulate thought and propose potential research directions. METHOD: A working group of experts in swallowing and dysphagia reviews 10 principles of neural plasticity and integrates these advancing neural plastic concepts with swallowing and clinical dysphagia literature for translation into treatment paradigms. In this context, dysphagia refers to disordered swallowing associated with central and peripheral sensorimotor deficits associated with stroke, neurodegenerative disease, tumors of the head and neck, infection, or trauma. RESULTS AND CONCLUSIONS: The optimal treatment parameters emerging from increased understanding of neural plastic principles and concepts will contribute to evidence-based practice. Integrating these principles will improve dysphagia rehabilitation directions, strategies, and outcomes. A strategic plan is discussed, including several experimental paradigms for the translation of these principles and concepts of neural plasticity into the clinical science of rehabilitation for oropharyngeal swallowing disorders, ultimately providing the evidence to substantiate their translation into clinical practice

The effect of membrane electrical activity on spiral ganglion neuron (SGN) neurite growth remains unknown despite its relevance to cochlear implant technology. We demonstrate that membrane depolarization delays the initial formation and inhibits the subsequent extension of cultured SGN neurites. This inhibition depends directly on the level of depolarization with higher levels of depolarization causing retraction of existing neurites. Cultured SGNs express subunits for L-type, N-type, and P/Q type voltage-gated calcium channels (VGCCs) and removal of extracellular Ca(2+) or treatment with a combination of L-type, N-type, and P/Q-type VGCC antagonists rescues SGN neurite growth under depolarizing conditions. By measuring the fluorescence intensity of SGNs loaded with the fluorogenic calpain substrate t-butoxy carbonyl-Leu-Met-chloromethylaminocoumarin (20 muM), we demonstrate that depolarization activates calpains. Calpeptin (15 muM), a calpain inhibitor, prevents calpain activation by depolarization and rescues neurite growth in depolarized SGNs suggesting that calpain activation contributes to the inhibition of neurite growth by depolarization