Christian Head

SALIVARY DUCT CARCINOMA: A CLINICAL AND HISTOLOGIC REVIEW WITH IMPLICATIONS FOR TRASTUZUMAB THERAPY

Salivary duct carcinoma (SDC) is an aggressive tumor of the head and neck with a poor prognosis. The objective was to study SDC and recommend the use of trastuzumab as adjuvant therapy.

Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

Prostate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self‐renewal and tissue regeneration capability in the present study.

Increased Lysis of Stem Cells but Not Their Differentiated Cells by Natural Killer Cells; De-Differentiation or Reprogramming Activates NK Cells

The aims of this study are to demonstrate the increased lysis of stem cells but not their differentiated counterparts by the NK cells and to determine whether disturbance in cell differentiation is a cause for increased sensitivity to NK cell mediated cytotoxicity. Increased cytotoxicity and augmented secretion of IFN-γ were both observed when PBMCs or NK cells were co-incubated with primary UCLA oral squamous carcinoma stem cells (UCLA-OSCSCs) when compared to differentiated UCLA oral squamous carcinoma cells (UCLA-OSCCs). In addition, human embryonic stem cells (hESCs) were also lysed greatly by the NK cells. Moreover, NK cells were found to lyse human Mesenchymal Stem Cells (hMSCs), human dental pulp stem cells (hDPSCs) and human induced pluripotent stem cells (hiPSCs) significantly more than their differentiated counterparts or parental lines from which they were derived. It was also found that inhibition of differentiation or reversion of cells to a less-differentiated phenotype by blocking NFκB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-γ. Taken together, these results suggest that stem cells are significant targets of the NK cell cytotoxicity. However, to support differentiation of a subset of tumor or healthy untransformed primary stem cells, NK cells may be required to lyse a number of stem cells and/or those which are either defective or incapable of full differentiation in order to lose their cytotoxic function and gain the ability to secrete cytokines (split anergy). Therefore, patients with cancer may benefit from repeated allogeneic NK cell transplantation for specific elimination of cancer stem cells.

Lamina Propria Replacement Therapy with Cultured Autologous Fibroblasts for Vocal Fold Scars

OBJECTIVES: To develop a canine model of vocal fold scar and to evaluate its treatment with lamina propria replacement therapy using autologous cultured fibroblasts. MATERIALS AND METHODS: Full thickness of the lamina propria layer in canine vocal folds was injured with a laser. Fibroblasts were cultured and expanded in the laboratory from a buccal mucosal biopsy. The scarred vocal folds were treated with 3 weekly injections of fourth, fifth, and sixth passage autologous fibroblasts. Mucosal waves and acoustic parameters were measured at baseline, after scarification, and several months after injection therapy. Histologic evaluation of the vocal folds for fibroblasts, collagen, elastin, reticulin, and hyaluronic acid was performed. RESULTS: Nine beagle dogs were used, and 1 animal served as control. Vocal fold scarring resulted in absent or severely limited mucosal waves and significantly worse acoustic parameters. Significant improvements in mucosal waves and acoustic parameters were obtained after lamina propria replacement therapy. After therapy, mucosal waves became normal in 4 animals and near normal in the other 4. No statistical difference was found in mucosal waves between baseline and post-therapy. All animals tolerated therapy without complications. The treated vocal folds demonstrated an increased density of fibroblasts, collagen, and reticulin, a decreased density of elastin, and no change in hyaluronic acid. CONCLUSIONS AND SIGNIFICANCE: Therapeutic options for vocal fold scars are limited. Lamina propria replacement therapy in the form of autologous cultured fibroblasts improves mucosal pliability and returns normal or near normal mucosal waves in experimentally scarred vocal folds. This novel therapeutic modality may hold new promise for treating vocal fold scars.

Microvascular flap reconstruction of the mandible: A comparison of bone grafts and bridging plates for restoration of mandibular continuity

OBJECTIVE To compare the efficacy of vascularized bone grafts and bridging mandibular reconstruction plates for restoration of mandibular continuity in patients who undergo free flap reconstruction after segmental mandibulectomy. Study design and setting A total of 210 patients underwent microvascular flap reconstruction after segmental mandibulectomy. The rate of successful restoration of mandibular continuity in 151 patients with vascularized bone grafts was compared to 59 patients with soft tissue free flaps combined with bridging plates. RESULTS Mandibular continuity was restored successfully for the duration of the follow-up period in 94% of patients who received bone grafts compared with 92% of patients with bridging mandibular reconstruction plates. This difference was not statistically significant. In patients who received bone grafts, most cases of reconstructive failure occurred during the perioperative period and were due to patient death or free flap thrombosis. In patients who received bridging plates, all instances of reconstructive failure were delayed for several months and were due to hardware extrusion or plate fracture. CONCLUSIONS Vascularized bone-containing free flaps are preferred for reconstruction of most segmental mandibulectomy defects in patients undergoing microvascular flap reconstruction. However, use of a soft tissue flap with a bridging mandibular reconstruction plate is a reasonable alternative in patients with lateral oromandibular defects when the nature of the defect favors use of a soft tissue free flap. SIGNIFICANCE Both bone grafts and bridging plates represent effective methods of restoring mandibular continuity following segmental mandibulectomy, with the former being the preferred technique for patients undergoing microvascular reconstruction.

Salvage surgery with free flap reconstruction: Factors affecting outcome after treatment of recurrent head and neck squamous carcinoma

Objective: To determine factors predicting the outcome after salvage surgery with microvascular flap reconstruction for recurrent squamous cell cancer (SCC) of the head and neck.

Emerging Mechanisms of Immunosuppression in Oral Cancers

Mounting effective anti-tumor immune responses against tumors by both the innate and adaptive immune effectors is important for the clearance of tumors. However, accumulated evidence indicates that immune responses that should otherwise suppress or eliminate transformed cells are themselves suppressed by the function of tumor cells in a variety of cancer patients, including those with oral cancers. Signaling abnormalities, spontaneous apoptosis, and reduced proliferation and function of circulating natural killer cells (NK), T-cells, dendritic cells (DC), and tumor-infiltrating lymphocytes (TILs) have been documented previously in oral cancer patients. Several mechanisms have been proposed for the functional deficiencies of tumor-associated immune cells in oral cancer patients. Both soluble factors and contact-mediated immunosuppression by the tumor cells have been implicated in the inhibition of immune cell function and the progression of tumors. More recently, elevated levels and function of key transcription factors in tumor cells, particularly NFκB and STAT3, have been shown to mediate immune suppression in the tumor microenvironment. This review will focus on these emerging mechanisms of immunosuppression in oral cancers.

Economic advantages to a distraction decision tree model for management of neonatal upper airway obstruction.

Background: Neonatal upper airway obstruction demands urgent attention. Tracheostomy can prove to be lifesaving but has morbidities. Recently, the authors found reduced morbidity/mortality when using a distraction decision tree model compared with conventional “case-by-case” management. In this current study, the authors assess the long-term costs of (1) a decision tree model versus conventional treatment and (2) tracheostomy versus distraction osteogenesis. Methods: An inpatient cost-matrix analysis study on neonates with upper airway obstruction and micrognathia was performed (n = 149). In Part I, conventionally treated neonates managed on a case-by-case basis received home monitoring or a tracheostomy. Decision tree model–managed newborns had specialist consultations and diagnostic testing to determine whether home monitoring, tracheostomy, or distraction osteogenesis would be implemented. In Part II, tracheostomy treatment was compared directly to distraction osteogenesis. Results: In Part I (conventional versus decision tree model), taking into account the costs of the distraction, tracheostomy, hospital stay, diagnostic studies, physician fees, and emergency department visits, the total per patient treatment cost was 1.5 greater in the conventional treatment group (

Coengagement of CD16 and CD94 Receptors Mediates Secretion of Chemokines and Induces Apoptotic Death of Naive Natural Killer Cells

332,673) compared with the decision tree model (

Potential contribution of naïve immune effectors to oral tumor resistance: role in synergistic induction of VEGF, IL-6, and IL-8 secretion

225,998) (p < 0.05). In Part II (tracheostomy versus distraction osteogenesis), the total per-patient treatment cost in the tracheostomy group was two times greater than in the distraction group (