ABSTRACT
Aberrant epidermal growth factor (EGF) signaling is associated with tumor growth in squamous cell carcinoma of the head and neck in humans (HNSCC), and is a major focus of targeted therapy. Cetuximab, a monoclonal antibody against EGFR, has been successful at prolonging survival but has only a 10% tumor shrinkage response rate in a clinical setting. The goal of this study was to compare dacomitinib (PF-00299804), a next generation small molecule tyrosine kinase inhibitor that irreversibly blocks multiple HER family receptors (HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases), to cetuximab, the current FDA approved anti-EGFR medication for HNSCC and erlotinib, an EGFR specific small molecule tyrosine kinase inhibitor. Dacomitinib, erlotinib and cetuximab were tested in a panel of 27 HNSCC cell lines. Treatment with 100 ug/ml of cetuximab or 1 uM of erlotinib inhibited growth by at least 50% in 7/27 cell lines, while treatment with 1 uM of dacomitinib had similar growth inhibition in 17/27 lines. Cell lines representing three levels of sensitivity to dacomitinib were further examined using Western blots, cell cycle and apoptosis analysis. Treatment with 100 nM of dacomitinib reduced EGFR activity and downstream AKT and ERK pathways more effectively than treatment with 100 ug/ml of cetuximab in all ten tested lines. Although both compounds induced apoptosis at similar levels, dacomitinib caused greater G0/G1 arrest. Sensitivity to EGFR blockade was associated with levels of EGFR and ERK and was not associated with common oncogenic mutations and copy number variations. Phosphorylated and total EGFR and ERK levels correlate with sensitivity to both cetuximab and dacomitinib. Three of the four lines in the exquisitely sensitive group had the highest levels of phosphorylated and total EGFR and ERK among the ten lines selected, while the three resistant lines collectively had the lowest levels. Neither pAKT nor tAKT was associated with sensitivity.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Carcinoma, Squamous Cell/drug therapy , Cell Proliferation/drug effects , Drug Resistance, Neoplasm/drug effects , Head and Neck Neoplasms/drug therapy , Protein Kinase Inhibitors/pharmacology , Quinazolinones/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Blotting, Western , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Cell Cycle/drug effects , Cetuximab , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Erlotinib Hydrochloride , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/pathology , Humans , In Situ Hybridization, Fluorescence , Mutation/genetics , Phosphatidylinositol 3-Kinases/genetics , Phosphorylation/drug effects , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins p21(ras) , Quinazolines/pharmacology , Signal Transduction/drug effects , Tumor Cells, Cultured , ras Proteins/geneticsABSTRACT
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 ($332,673) compared with the decision tree model ($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 ($382,246 versus $193,128) (p<0.05). CONCLUSIONS: In treating newborns with micrognathia and upper airway obstruction, a decision tree model with mandibular distraction decreases long-term health care costs compared with conventional treatment. Furthermore, when comparing distraction to tracheostomy, similar decreases in long-term health care costs occurred.
Subject(s)
Airway Obstruction/economics , Airway Obstruction/surgery , Decision Trees , Micrognathism/economics , Micrognathism/surgery , Costs and Cost Analysis , Decision Support Techniques , Humans , Infant, Newborn , Osteogenesis, Distraction/economics , Tracheostomy/economicsABSTRACT
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-gamma 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 NFkappaB or targeted knock down of COX2 in monocytes significantly augmented NK cell cytotoxicity and secretion of IFN-gamma. 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.
Subject(s)
Killer Cells, Natural/immunology , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Animals , Blotting, Western , Cell Differentiation/genetics , Cell Differentiation/physiology , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma/metabolism , Interleukin-2/pharmacology , Interleukin-6/metabolism , Interleukin-8/metabolism , Killer Cells, Natural/drug effects , Mouth Neoplasms/pathology , Neoplasms, Squamous Cell/pathology , Neoplastic Stem Cells/immunology , Stem Cells/cytology , Stem Cells/metabolismABSTRACT
Nasopharyngeal stenosis as a postoperative complication following pharyngeal surgery (tonsillectomy/adenoidectomy) is rare and may be difficult to treat. All patients with severe nasopharyngeal stenosis treated at UCLA with a bilateral Z-pharyngoplasty procedure from 1999 to 2006 were studied (n = 6). Degree of pharyngeal stenosis preoperatively and following a bilateral Z-pharyngoplasty was graded 0-4 based on (1) symptomatology (snoring, hyponasal speech, difficulty with nasal breathing, difficulty breathing during exercise, obstructive sleep apnea, daytime fatigue, anosmia, rhinorrea, dysphagia, or difficulty in blowing nose) and (2) measurement of stricture at the time of direct nasolaryngoscopy. Nasopharyngeal stenosis after pharyngeal surgery (adenotonsillectomy--67%, uvuloplasty--17%, pharyngoplasty--17%) failed to be alleviated by a mean of 2.3 procedures (kenalog injection or scar excision) and required corrective bilateral Z-pharyngoplasty a mean of 9.2 months after the original surgery. Symptomatic grading of the nasopharyngeal stenosis improved from a mean score of 3.3 (severe stenosis) preoperatively to a score of 0.2 (minimal to no stenosis) in follow-up. Endoscopic stricture measurement improved from 6.1 x 6.3 mm preoperatively to 28.1 x 39.3 mm in follow-up. Bilateral Z-pharyngoplasty was effective in alleviating severe postsurgical nasopharyngeal stenosis.
Subject(s)
Adenoidectomy/adverse effects , Nasopharyngeal Diseases/surgery , Plastic Surgery Procedures/methods , Surgical Flaps , Tonsillectomy/adverse effects , Adenoidectomy/methods , Airway Obstruction/etiology , Airway Obstruction/surgery , Child , Child, Preschool , Cohort Studies , Constriction, Pathologic/etiology , Constriction, Pathologic/surgery , Female , Follow-Up Studies , Graft Rejection , Graft Survival , Humans , Laryngoscopy/methods , Male , Nasal Obstruction/etiology , Nasal Obstruction/surgery , Nasopharyngeal Diseases/etiology , Pharynx/surgery , Postoperative Complications/surgery , Retrospective Studies , Risk Assessment , Tonsillectomy/methods , Treatment OutcomeABSTRACT
BACKGROUND: 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. METHODS: Prostaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice. RESULTS: Prostate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells. CONCLUSION: Human prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells.
Subject(s)
Epithelial Cells/physiology , Prostate/cytology , Stem Cells/physiology , AC133 Antigen , Adult , Aged , Antigens, CD/analysis , Cell Lineage , Gene Rearrangement , Glycoproteins/analysis , Humans , Hyaluronan Receptors/analysis , Immunohistochemistry , Integrin alpha6/analysis , Male , Middle Aged , Oncogene Proteins, Fusion/analysis , Oncogene Proteins, Fusion/genetics , Peptides/analysis , Prostatic Neoplasms/pathology , RegenerationABSTRACT
Prostate cancer metastatic to the parotid gland is exceedingly rare, as only 10 cases have been previously reported in the literature. Symptoms may mimic a parotid infection or suggest a primary parotid tumor. We report a new case of carcinoma of the prostate metastatic to the parotid. The tumor was painful and had invaded the mandible. Fine-needle aspiration of the mass and immunohistochemical staining for prostate-specific antigen confirmed the diagnosis. The patient died 1 month later of an unrelated cause.
Subject(s)
Carcinoma/radiotherapy , Carcinoma/secondary , Mandibular Neoplasms/radiotherapy , Mandibular Neoplasms/secondary , Parotid Neoplasms/radiotherapy , Parotid Neoplasms/secondary , Prostatic Neoplasms/pathology , Prostatic Neoplasms/radiotherapy , Diagnosis, Differential , Humans , Male , Middle Aged , Neoplasm Staging , Pain/diagnosis , Pain MeasurementABSTRACT
Parathyroid cysts are rare lesions that can present clinically as low neck masses. The clinical diagnosis of parathyroid cyst can be challenging and requires a high level of suspicion as it often mimics a thyroid nodule. The cyst occasionally can cause compressive symptoms such as dysphagia or dyspnea. When it occurs in the mediastinum, it can cause recurrent laryngeal nerve paralysis. In this report, we present a patient with a hyperfunctional parathyroid cyst in association with a papillary thyroid carcinoma. In addition, we briefly discuss the current literature on parathyroid cyst. This case is unusual in its clinical presentation in that the parathyroid cyst mimicked a thyroid goiter.
Subject(s)
Cysts/diagnosis , Goiter/diagnosis , Parathyroid Diseases/diagnosis , Parathyroidectomy/methods , Thyroidectomy/methods , Aged , Biopsy, Fine-Needle , Cysts/surgery , Diagnosis, Differential , Follow-Up Studies , Humans , Male , Parathyroid Diseases/surgery , Tomography, X-Ray ComputedABSTRACT
Freshly isolated untreated NK cells undergo rapid apoptosis and lose their cytotoxic function upon the addition of F(ab')2 fragment of anti-CD16 antibodies. Loss of NK cell cytotoxic function after treatment with F(ab')2 fragment of anti-CD16 antibody can be seen against K562 and UCLA-2 oral tumor cells when either added immediately in the co-cultures of NK cells with the tumor cells or after pre-treatment of NK cells with the antibody before their addition to the tumor cells. Addition of Interleukin-2 (IL-2) in combination with anti-CD16 antibody to NK cells delayed the induction of DNA fragmentation in NK cells, and even though decreased cytotoxicity could still be observed against K562 and UCLA-2 oral tumors when compared to IL-2 alone treated NK cells, the cytotoxicity levels remained relatively higher and approached those obtained by untreated NK cells in the absence of antibody treatment. No increases in IFN-gamma, Granzymes A and B, Perforin and TRAIL genes could be seen in NK cells treated with anti-CD16 antibody. Neither secretion of IFN-gamma nor increased expression of CD69 activation antigen could be observed after the treatment of NK cells with anti-CD16 antibody. Furthermore, IL-2 mediated increase in CD69 surface antigens was down-modulated by anti-CD16 antibody. Finally, the addition of anti-CD16 antibody to co-cultures of NK cells with tumor target cells was not inhibitory for the secretion of VEGF by oral tumor cells, unlike those co-cultured with untreated or IL-2 treated NK cells. Thus, binding and triggering of CD16 receptor on NK cells may enhance oral tumor survival and growth by decreased ability of NK cells to suppress VEGF secretion or induce tumor cell death during the interaction of NK cells with oral tumor cells.
Subject(s)
Antibodies/immunology , Carcinoma, Squamous Cell/pathology , Cytotoxicity, Immunologic , Immunoglobulin Fab Fragments/pharmacology , Killer Cells, Natural/immunology , Receptors, IgG/immunology , Tongue Neoplasms/pathology , Antibodies/chemistry , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/immunology , Carcinoma, Squamous Cell/immunology , Cell Death , Cell Line, Tumor , DNA Fragmentation , GPI-Linked Proteins , Humans , Immunoglobulin Fab Fragments/immunology , Interferon-gamma/metabolism , Killer Cells, Natural/pathology , Lectins, C-Type , Tongue Neoplasms/immunology , Vascular Endothelial Growth Factor A/metabolismABSTRACT
The aim of this study is to identify the phenotype of resistant oral tumors, and to delineate the contribution of immune effectors to resistance of oral tumors. UCLA-1 oral tumors which were resistant to NK cell mediated cytotoxicity secreted increased amounts of IL-6, IL-1beta, GM-CSF, and IL-8 when cultured with or without immune effectors. In addition, the levels of vascular endothelial growth factor (VEGF) secretion in the co-cultures of naïve immune effectors with UCLA-1 rose significantly when compared to tumor cells alone. IL-2 activated NK cells decreased VEGF secretion in all tumor cells. However, NK cells which were induced to undergo cell death with anti-CD16 antibody were not only unable to decrease VEGF secretion, but they also contributed further to the increase in VEGF secretion by oral tumors. Overall, we show in this paper that naïve as well as non-viable immune effectors may contribute to the growth and resistance of oral tumors by triggering the secretion of key tumor cell growth factors.
Subject(s)
Interleukin-6/metabolism , Interleukin-8/metabolism , Killer Cells, Natural/immunology , Mouth Neoplasms/immunology , Mouth Neoplasms/metabolism , Tumor Escape/immunology , Vascular Endothelial Growth Factor A/metabolism , Cell Death/immunology , Cell Line, Tumor , Coculture Techniques , Cytotoxicity, Immunologic , Drug Synergism , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Interleukin-1beta/metabolism , Interleukin-2/pharmacology , Killer Cells, Natural/drug effects , Phenotype , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To identify the incidence of hardware and bone-healing complications in patients who underwent locking mandibular reconstruction plate (LMRP) fixation of vascularized bone grafts for reconstruction of segmental mandibular defects. DESIGN: Case series. SETTING: Academic tertiary care medical center. PATIENTS: One hundred one patients who had undergone LMRP fixation of vascularized bone grafts for reconstruction of segmental mandibular defects with a minimum follow-up of 6 months. MAIN OUTCOME MEASURES: Association of patient- and defect-related characteristics with the incidence of loose screws, osteosynthesis nonunion, and complications necessitating hardware removal. RESULTS: The incidence of loose screws was 0.8% in 984 locking screws implanted. The incidence of nonunion was 0.7% in 290 osteosyntheses. Overall, 15 of 101 LMRPs (14.8%) were removed because of hardware-related complications, with plate extrusion (n = 10) the most common complication necessitating hardware removal. Pathologic diagnosis (P = .002), previous treatment with hyperbaric oxygen (P < .001), radiation therapy (P < .001), and cancer recurrence (P = .03) were statistically significant predictors of LMRP-related complications at univariate analysis. At multivariate analysis, previous treatment with hyperbaric oxygen (P < .046) remained a statistically significant predictor of LMRP-related complications. CONCLUSIONS: In patients undergoing mandibular reconstruction, LMRPs are highly effective for fixation of vascularized bone grafts, with a high incidence of bone-graft healing and a low incidence of complications related to loose screws. Nevertheless, there remains a 15% incidence of hardware-related complications, most related to hardware extrusion. Previous treatment with hyperbaric oxygen is a statistically significant predictor of LMRP-related complications.
Subject(s)
Bone Plates , Bone Screws , Bone Transplantation/methods , Fibula/transplantation , Mandible/transplantation , Mandibular Neoplasms/surgery , Plastic Surgery Procedures/instrumentation , California/epidemiology , Device Removal , Equipment Failure , Female , Fibula/blood supply , Follow-Up Studies , Humans , Incidence , Male , Mandible/blood supply , Postoperative Complications/epidemiology , Retrospective Studies , Treatment OutcomeSubject(s)
Pharyngeal Diseases/diagnosis , Pharyngeal Diseases/physiopathology , Uvula/abnormalities , Uvula/physiopathology , Anti-Inflammatory Agents/therapeutic use , Edema/diagnosis , Edema/physiopathology , Female , Histamine Antagonists/therapeutic use , Humans , Middle Aged , Pharyngeal Diseases/drug therapyABSTRACT
The inhibitory role of TNF-alpha on survival of naïve and IL-2 treated NK cells has been demonstrated in the past. However, its effect on the function of these cells against tumor cells, in particular against oral tumors has not been established. We investigated the significance of secreted TNF-alpha in death and functional loss of splenocytes and NK cells in ex-vivo cultures with oral tumors. Oral tumors trigger potent secretion of TNF-alpha by human and murine immune effectors. Absence of TNF-alpha increases the cytotoxic activity and secretion of IFN-gamma by IL-2 treated splenocytes and NK cells in co-cultures with MOK L2D1+/p53-/- oral tumor cells. IL-2 treated splenocytes and NK cells from TNF-alpha -/- mice survive and proliferate more when compared to cells from TNF-alpha +/+ mice. Cell death induced by F. nucleatum, an oral bacteria, in TNF-alpha -/- splenocytes are considerably lower than that induced in TNF-alpha +/+ splenocytes where potent release of TNF-alpha is reproducibly observed. Addition of exogenous rTNF-alpha to IL-2 treated splenocytes and NK cells decreased survival and function of splenocytes and NK cells obtained from TNF-alpha -/- mice against oral tumors. These findings suggest that potent induction of TNF-alpha during interaction of immune effectors with oral tumors and/or oral bacteria is an important factor in decreasing the function and survival of cytotoxic immune effectors. Strategies to neutralize TNF-alpha may be beneficial in the treatment of oral cancers.
Subject(s)
Killer Cells, Natural/immunology , Mouth Neoplasms/immunology , Tumor Necrosis Factor-alpha/biosynthesis , Animals , Apoptosis/immunology , Cell Line, Tumor , Cell Survival/immunology , Humans , Killer Cells, Natural/pathology , Mice , Mice, Knockout , Mouth Neoplasms/metabolism , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/deficiency , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/physiologyABSTRACT
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. STUDY DESIGN: This is a retrospective analysis of patients treated at an academic medical center. METHODS: One hundred six patients underwent salvage surgery and microvascular flap reconstruction after prior unsuccessful cancer treatment using surgery, radiation, or chemotherapy. All patients had a follow-up interval after salvage surgery of at least 24 months unless cancer rerecurrence occurred within 24 months after salvage surgery. Factors including age, sex, comorbidity level, tobacco use, alcohol use, disease-free interval since prior therapy, prior radiation, prior chemotherapy, prior surgery, recurrent tumor T class, recurrent tumor N class, recurrent cancer stage, and tumor location were examined to determine their association with cancer rerecurrence after salvage surgery. Successful treatment was defined as patients who remained free from cancer rerecurrence for a minimum 2 year period after salvage surgery. RESULTS: Advanced recurrent T class (P = .02) was significantly associated with cancer recurrence. Recurrent cancer stage and patient smoking status approached statistical significance (P = .06). CONCLUSION: Patients with recurrent T1 and T2 class are the best candidates for salvage surgery and microvascular flap reconstruction for treatment of recurrent SCC of the head and neck. Patients with T3 and T4 class recurrent cancers and patients who continue to smoke after initial diagnosis and treatment of head and neck SCC are poor candidates to undergo salvage surgery.
Subject(s)
Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/surgery , Plastic Surgery Procedures/methods , Salvage Therapy/methods , Skin Transplantation/methods , Surgical Flaps , Adult , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/radiotherapy , Female , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/radiotherapy , Humans , Male , Microsurgery/methods , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Staging , Prognosis , Radiotherapy/adverse effects , Radiotherapy/statistics & numerical data , Retrospective Studies , Risk Factors , Survival RateABSTRACT
BACKGROUND: 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. METHODS: A retrospective chart review of patients seen between 1993 and 2006 was performed. Tumor specimens were examined for HER-2 protein overexpression via immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. RESULTS: Of the 7 patients with SDC, 57% had tumors arising in the parotid gland, the majority having facial nerve paralysis, 71% with nodal disease, and 43% having recurrence. All samples were HER-2 positive on IHC. Three patients had FISH-positive tumors, recurrent disease, and received trastuzumab therapy; 1 of the 3 died after 20 months and a second has shown disappearance of metastatic disease. CONCLUSIONS: Trastuzumab is effective in treating HER-2-positive breast cancer. Given immunohistochemical similarities between SDC and ductal carcinoma of the breast, patients with FISH-positive HER-2/neu SDC should be considered for trastuzumab therapy.
Subject(s)
Antibodies, Monoclonal/administration & dosage , Antineoplastic Agents/administration & dosage , Neoplasm Recurrence, Local/therapy , Salivary Gland Neoplasms/therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/administration & dosage , Carcinoma, Ductal/metabolism , Carcinoma, Ductal/mortality , Carcinoma, Ductal/therapy , Carcinoma, Intraductal, Noninfiltrating/metabolism , Carcinoma, Intraductal, Noninfiltrating/mortality , Carcinoma, Intraductal, Noninfiltrating/therapy , Chemotherapy, Adjuvant , Facial Paralysis/etiology , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Paclitaxel/administration & dosage , Radiotherapy, Adjuvant , Receptor, ErbB-2/metabolism , Retrospective Studies , Salivary Gland Neoplasms/metabolism , Salivary Gland Neoplasms/mortality , TrastuzumabABSTRACT
PURPOSE: The aim of the study was to determine the sensitivity of preoperative positron emission tomography (PET) scans in the detection of primary tumors of the tonsils. MATERIALS AND METHODS: We conducted a retrospective review of 46 patients treated at a university medical center for occult tonsillar cancer during the years 2002 to 2004. We identified patients who underwent a preoperative PET scan to locate an unknown primary tumor. Fusion computed tomography with PET (PET/CT) was used to further delineate anatomic localization to the tonsil area. A positive PET/CT scan was defined as asymmetric increased tracer uptake in the tonsil and/or tonsillar fossa ipsilateral to the tonsillar cancer site when compared with the contralateral site. A negative PET/CT scan was defined as equivocal symmetric tracer uptake bilaterally. RESULTS: Of the 46 patients, 6 (13.0%) had pretreatment PET scans. Of these 6 patients, 16.7% (n = 1) had positive PET, 66.7% (n = 4) had negative PET, and 16.7% (n = 1) demonstrated increased tracer uptake in tonsils bilaterally greater on the side contralateral to the cancer. In this group, PET scans had a sensitivity of 0.167 and false-negative ratio of 0.667 for tonsillar cancer detection. CONCLUSIONS: Although the patient population in this study is small (n = 6), the findings suggest that PET/ CT scans may offer a low sensitivity in detection of primary tonsillar cancers. However, PET/CT scans still have a significant role in the detection of other unknown primary head and neck tumors. Technical reasons for this finding are discussed.
Subject(s)
Neoplasms, Unknown Primary/diagnostic imaging , Positron-Emission Tomography , Preoperative Care , Tonsillar Neoplasms/diagnostic imaging , Aged , Carcinoma, Squamous Cell/diagnostic imaging , Fluorodeoxyglucose F18/pharmacokinetics , Humans , Lymphoma/diagnostic imaging , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Radiopharmaceuticals/pharmacokinetics , Retrospective Studies , Sensitivity and Specificity , Tomography, X-Ray ComputedABSTRACT
CONCLUSION: Both CT and MRI defined the extent of histologically proven recurrent disease, although it was impossible to radiographically distinguish recurrent disease from postoperative scar tissue or mucoperiosteal thickening. OBJECTIVE: A retrospective analysis of radiographic findings of patients with known inverted papilloma (IP) was performed to identify those characteristics that should prompt preoperative biopsy in patients with polypoid nasal masses. MATERIALS AND METHODS: The radiologic studies from a group of 77 patients with biopsy-proven IP of the nasal cavity or paranasal sinuses were reviewed. Fifty-three computed tomography (CT) scans, 17 cases of plain sinus radiography and 7 cases of magnetic resonance imaging (MRI) were analyzed. RESULTS: Although no preoperative MRI examinations were available for comparison, CT was the most helpful study for evaluation of primary, nonrecurrent inverted papilloma. CT demonstrated disease-related abnormalities in 90% of studies. The finding of frequent unilateral bony remodeling was demonstrated in 43% of scans. Plain sinus X-rays were abnormal in 70% of cases of primary tumor, with all positive studies showing nonspecific unilateral opacification of the maxillary antrum.
Subject(s)
Magnetic Resonance Imaging , Nose Neoplasms/diagnosis , Papilloma, Inverted/diagnosis , Paranasal Sinus Neoplasms/diagnosis , Tomography, X-Ray Computed , Biopsy , Bone Remodeling/physiology , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Nasal Cavity/pathology , Nasal Cavity/surgery , Nasal Polyps/diagnosis , Nasal Polyps/pathology , Nasal Polyps/surgery , Nose Neoplasms/pathology , Nose Neoplasms/surgery , Papilloma, Inverted/pathology , Papilloma, Inverted/surgery , Paranasal Sinus Neoplasms/pathology , Paranasal Sinus Neoplasms/surgery , Paranasal Sinuses/pathology , Paranasal Sinuses/surgery , Sensitivity and SpecificityABSTRACT
BACKGROUND: The role of fibula free flaps for reconstruction of through-and-through oromandibular defects is examined. METHODS: Thirty-four patients underwent reconstruction of through-and-through oromandibular defects using fibula free flaps that contain large, bilobed skin paddles for simultaneous reconstruction of intraoral mucosa and external skin. We examined the incidence of wound healing complications, the need for revision reconstructive surgery, and factors affecting the incidence of complications. RESULTS: Wound healing complications occurred in 50% of patients. There was a relatively high incidence of partial flap necrosis (26%) and revision surgery (41%). The area of the flap skin paddle was significantly associated with the risk of partial flap necrosis and the need for revision surgery. CONCLUSIONS: Many through-and-through oromandibular defects can be successfully reconstructed using a fibula free flap that contains a large, bilobed skin paddle. However, wound healing complications are increased when the flap skin paddle area exceeds 300 cm2.
Subject(s)
Carcinoma, Squamous Cell/surgery , Mandibular Neoplasms/surgery , Surgical Flaps , Adult , Aged , Aged, 80 and over , Facial Neoplasms/surgery , Female , Humans , Male , Middle Aged , Necrosis , Plastic Surgery Procedures , Reoperation , Surgical Flaps/pathology , Wound HealingABSTRACT
BACKGROUND: : The outcome of patients undergoing rigid plate fixation of symphyseal mandibular osteotomies for exposure, resection, and reconstruction of tumors in the oral cavity or oropharynx was analyzed to determine the impact of hardware selection on complications. METHODS: : Forty-five patients underwent titanium plate rigid internal fixation of mandibular osteotomies during cancer resection and free flap reconstruction at an academic medical center. The incidence of hardware-related complications and mandibular nonunion was compared in patients receiving either locking hardware or nonlocking hardware. RESULTS: : The incidence of osteotomy-related complications in patients with an inferior border nonlocking mandibular fracture plate was 21%. In the patients with locking hardware or an inferior border nonlocking mandibular fracture plate combined with a tension band, there were no hardware-related complications and no mandibular nonunions. This difference was statistically significant (chi(2) = 6.01, p < .05). CONCLUSIONS: : Locking mandibular reconstruction plates are associated with fewer complications than inferior border nonlocking mandibular fracture plates for rigid fixation of mandibular osteotomies in patients undergoing resection of head and neck cancer.
Subject(s)
Fracture Fixation, Internal/instrumentation , Mouth Neoplasms/surgery , Oropharyngeal Neoplasms/surgery , Osteotomy/instrumentation , Adult , Aged , Bone Plates , Bone Screws , Equipment Design , Female , Fracture Fixation, Internal/adverse effects , Fractures, Ununited/etiology , Humans , Male , Mandibular Fractures/surgery , Middle Aged , Osteotomy/adverse effects , Reoperation , Surgical Flaps , Surgical Wound Infection/etiology , TitaniumABSTRACT
BACKGROUND: Conventional cancer therapy including surgery, radiation, and chemotherapy often are physically debilitating and largely ineffective in previously treated patients with recurrent head and neck squamous cell carcinoma (SCC). A natural photochemical, hypericin, could be a less invasive method for laser photodynamic therapy (PDT) of these recurrent head and neck malignancies. Hypericin has powerful photo-oxidizing ability, tumor localization properties, and fluorescent imaging capabilities as well as minimal dark toxicity. The current study defined hypericin PDT in vitro with human SCC cells before the cells were grown as tumor transplants in nude mice and tested as a model for hypericin induced tumor fluorescence and PDT via laser fiberoptics. METHODS: SNU squamous carcinoma cells were grown in tissue culture, detached from monolayers with trypsin, and incubated with 0.1 microg to 10 microg/ml of hypericin before exposure to laser light at 514, 550, or 593 nm to define optimal dose, time, and wavelength for PDT of tumor cells. The SCC cells also were injected subcutaneously in nude mice and grown for 6-8 weeks to form tumors before hypericin injection and insertion of fiberoptics from a KTP532 surgical laser to assess the feasibility of this operating room instrument in stimulating fluorescence and PDT of tumors. RESULTS: In vitro testing revealed a hypericin dose of 0.2-0.5 microg/ml was needed for PDT of the SCC cells with an optimal tumoricidal response seen at the 593 nm light absorption maximum. In vivo tumor retention of injected hypericin was seen for 7 to 10 days using KTP532 laser induced fluorescence and biweekly PDT via laser fiberoptics led to regression of SCC tumor transplants under 0.4 cm2 diameter, but resulted in progression of larger size tumors in the nude mice. CONCLUSION: In this preclinical study, hypericin was tested for 514-593 nm dye laser PDT of human SCC cells in vitro and for KTP532 surgical laser targeting of SCC tumors in mice. The results suggest hypericin is a potent tumor imaging agent using this surgical laser that may prove useful in defining tumor margins and possibly in sterilizing post-resection margins. Deeply penetrating pulsed infrared laser emissions will be needed for PDT of larger and more inaccessible tumors.